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Clinical Trial Results:
A Randomized Double-Blind Phase 1b/2 Combined Staggered Multiple Dose Escalation Study of BOS161721 in Systemic Lupus Erythematosus (SLE) Patients on a Background of Limited Standard of Care

Summary
EudraCT number	2018-000305-23
Trial protocol	BG HU RO
Global end of trial date	26 Nov 2020

Results information
Results version number	v1(current)
This version publication date	13 Dec 2021
First version publication date	13 Dec 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

BOS161721-02

ISRCTN number

US NCT number

NCT03371251

WHO universal trial number (UTN)

Sponsor organisation name

Boston Pharmaceuticals

Sponsor organisation address

55 Cambridge Parkway, Suite 400, Cambridge, MA , United States, 02142

Public contact

Etienne Dumont, Boston Pharmaceuticals, Inc., +1 (484) 986 8699,

Scientific contact

Etienne Dumont, Boston Pharmaceuticals, Inc., +1 (484) 986 8699,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

26 Apr 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

26 Nov 2020

Global end of trial reached?

Yes

Global end of trial date

26 Nov 2020

Was the trial ended prematurely?

Main objective of the trial

Multiple ascending doses (MAD) Phase 1b primary objective: To assess safety, tolerability, and immunogenicity of repeat doses of BOS161721 (20, 60, and 120 mg) administered subcutaneously (SC) in adult subjects with moderate to severe systemic lupus erythematosus (SLE) on limited background standard of care treatment, in order to estimate the optimal dose. Proof of Concept (POC) Phase 2 Primary Objective: To demonstrate a superior effect of BOS161721 at the chosen dose compared with placebo for response on the SLE Responder Index 4 (SRI-4).

Protection of trial subjects

Prior to the initiation of the study at each study center, the clinical study protocol, amendments, patient information sheet, Informed Consent Form (ICF), and all other relevant study documentation were submitted to and approved by the responsible Independent Ethics Committee (IEC)/Institutional Review Board (IRB). The study was conducted in accordance with the principles set forth in the Declaration of Helsinki as amended in 2000, the Guidelines of the International Council for Harmonisation (ICH) on Good Clinical Practice (GCP) (CPMP/ICH/135/95), as well as the requirements of national drug and data protection laws, in particular the Health Insurance Portability and Accountability Act of 1996 (Public Law 104-191, 104th Congress), privacy regulations, and other applicable regulatory requirements. Prior to undergoing any study specific procedure, each potential study subject provided signed acknowledgement of their freely given informed consent. If the subject was willing to participate in the study, the ICF was signed and personally dated by the subject, the physician taking the consent and, if applicable, the designated person who explained the nature of the study.

Background therapy

Evidence for comparator

Actual start date of recruitment

10 Jan 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 18

Country: Number of subjects enrolled

Bulgaria: 7

Country: Number of subjects enrolled

Hungary: 4

Country: Number of subjects enrolled

United States: 49

Country: Number of subjects enrolled

Georgia: 19

Country: Number of subjects enrolled

Argentina: 9

Country: Number of subjects enrolled

Colombia: 2

Country: Number of subjects enrolled

Mexico: 6

Country: Number of subjects enrolled

Peru: 29

Worldwide total number of subjects

143

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

131

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study was conducted in in the United States, Georgia, Bulgaria, Hungary, Poland, Argentina, Columbia, Mexico, Romania, Ukraine, Philippines and Peru. The first subject was screened on 10 January 2018 and last subject last visit occurred on 26, November 2020.

Screening details

After successfully completing a screening phase, eligible subjects were randomized to a specified dose of BOS161721 or placebo. All assessments are screening phase were done as per the schedule of assessment table.

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Phase 1b: Placebo

Arm description

Subjects were randomized to receive subcutaneous (SC) dose of placebo. Subjects received a total of 7 SC monthly doses of placebo on Days 0, 30, 60, 90, 120, 150, and 180, followed by safety follow-up visits at Days 210, 240, and 270.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo was supplied for SC administration

Phase 1b: Cohort 1: BOS161721 20 mg

Arm description

Subjects were randomized to receive a 20 mg SC dose of BOS161721. Subjects received a total of 7 SC monthly doses of BOS161721 on Days 0, 30, 60, 90, 120, 150, and 180, followed by safety follow-up visits on at Days 210, 240, and 270.

Arm type

Experimental

Investigational medicinal product name

BOS161721

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

BOS161721 was supplied for SC administration

Phase 1b: Cohort 2: BOS161721 60 mg

Arm description

Subjects were randomized to receive a 60 mg SC dose of BOS161721. Subjects received a total of 7 SC monthly doses of BOS161721 on Days 0, 30, 60, 90, 120, 150, and 180, followed by safety follow-up visits on at Days 210, 240, and 270.

Arm type

Experimental

Investigational medicinal product name

BOS161721

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

BOS161721 was supplied for SC administration

Phase 1b: Cohort 3: BOS161721 120 mg

Arm description

Subjects were randomized to receive a 120 mg SC dose of BOS161721. Subjects received a total of 7 SC monthly doses of BOS161721 on Days 0, 30, 60, 90, 120, 150, and 180, followed by safety follow-up visits on at Days 210, 240, and 270.

Arm type

Experimental

Investigational medicinal product name

BOS161721

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

BOS161721 was supplied for SC administration

Phase 2: Placebo

Arm description

Subjects were randomized to receive a SC dose of placebo (as determined from Phase 1b of the study). Subjects received a total of 7 SC monthly doses of placebo on Days 0, 30, 60, 90, 120, 150, and 180, followed by safety follow-up visits on at Days 210, 240, and 270.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo was supplied for SC administration

Phase 2: BOS161721 120 mg

Arm description

Subjects were randomized to receive a 120 mg SC dose of BOS161721 (as determined from Phase 1b of the study). Subjects received a total of 7 SC monthly doses of BOS161721 on Days 0, 30, 60, 90, 120, 150, and 180, followed by safety follow-up visits on at Days 210, 240, and 270.

Arm type

Experimental

Investigational medicinal product name

BOS161721

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

BOS161721 was supplied for SC administration

Number of subjects in period 1	Phase 1b: Placebo	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Started	7	5	9	9	37	76
Completed	5	5	8	9	30	71
Not completed	2	0	1	0	7	5
Consent withdrawn by subject	1	-	1	-	2	2
Phase 1b: Pregnancy, Phase 2: fear of COVID- 19	1	-	-	-	2	3
Decision by Sponsor	-	-	-	-	2	-
Adverse event	-	-	-	-	1	-

Baseline characteristics

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Reporting group title

Phase 1b: Placebo

Reporting group description

Reporting group title

Phase 1b: Cohort 1: BOS161721 20 mg

Reporting group description

Reporting group title

Phase 1b: Cohort 2: BOS161721 60 mg

Reporting group description

Reporting group title

Phase 1b: Cohort 3: BOS161721 120 mg

Reporting group description

Reporting group title

Phase 2: Placebo

Reporting group description

Reporting group title

Phase 2: BOS161721 120 mg

Reporting group description

Reporting group values	Phase 1b: Placebo	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg	Phase 2: Placebo	Phase 2: BOS161721 120 mg	Total
Number of subjects	7	5	9	9	37	76	143
Age categorical
Units: Subjects
In utero							0
Preterm newborn infants (gestational age < 37 wks)							0
Newborns (0-27 days)							0
Infants and toddlers (28 days-23 months)							0
Children (2-11 years)							0
Adolescents (12-17 years)							0
Adults (18-64 years)							0
From 65-84 years							0
85 years and over							0
Age continuous
Units: years
arithmetic mean (standard deviation)	48.1 ( 17.67 )	50.0 ( 8.51 )	49.3 ( 11.31 )	47.3 ( 10.43 )	45.7 ( 12.52 )	44.5 ( 12.52 )	-
Gender categorical
Units: Subjects
Female	7	5	8	8	36	69	133
Male	0	0	1	1	1	7	10

End points

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Reporting group title

Phase 1b: Placebo

Reporting group description

Reporting group title

Phase 1b: Cohort 1: BOS161721 20 mg

Reporting group description

Reporting group title

Phase 1b: Cohort 2: BOS161721 60 mg

Reporting group description

Reporting group title

Phase 1b: Cohort 3: BOS161721 120 mg

Reporting group description

Reporting group title

Phase 2: Placebo

Reporting group description

Reporting group title

Phase 2: BOS161721 120 mg

Reporting group description

Primary: Phase 1b: Number of Subjects With Adverse Events (AEs)

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End point title

Phase 1b: Number of Subjects With Adverse Events (AEs) ^[1] ^[2]

End point description

The safety, tolerability, and immunogenicity of repeat doses of BOS161721 (20, 60, and 120 mg) administered SC were assessed in adult subjects with moderate to severe SLE on limited background standard of care treatment, in order to estimate the optimal dose.

End point type

Primary

End point timeframe

Up to Day 270

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical tests planned due to small sample size per cohort
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the primary endpoint for phase 1b only

End point values	Phase 1b: Placebo	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg
Number of subjects analysed	7	5	9	9
Units: Subjects
number (not applicable)
Any Treatment-Emergent Adverse Events (TEAE)	4	2	7	8
Related TEAE	1	0	1	0
Serious TEAE	1	0	2	0
Related Serious TEAE	0	0	0	0
CTCAE Grade 2 or Higher TEAE	4	2	6	7
Any Related CTCAE Grade 2 or Higher TEAE	1	0	0	0
Any CTCAE Grade 3 TEAE	1	1	2	0
Any Related CTCAE Grade 3 or Higher TEAE	0	0	0	0
Any CTCAE Grade 4 TEAE	0	0	0	0
TEAE Leading to Discontinuation of Study Treatment	0	0	0	0
Related TEAE Leading to Discont of Study Treatment	0	0	0	0
TEAE of Special Interest	0	0	0	0
Related TEAE of Special Interest	0	0	0	0
Dose-Limiting Toxicity	0	0	0	0
Related Dose-Limiting Toxicity	0	0	0	0
TEAE Resulting in Death	0	0	0	0
Related TEAE Resulting in Death	0	0	0	0
Injection Site Reaction	0	0	0	0

No statistical analyses for this end point

Primary: Phase 2: Number of Subjects With an SLE Responder Index 4 (SRI-4) Response at Day 210

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End point title

Phase 2: Number of Subjects With an SLE Responder Index 4 (SRI-4) Response at Day 210 ^[3]

End point description

The SRI-4 is a composite index of SLE disease improvement that consists of scores derived from the SLE Disease Activity Index 2000 (SLEDAI-2K), the British Isles Lupus Assessment Group (BILAG) 2004 Index and the Physician's Global Assessment (PGA). Response based on the SRI-4 is defined by: 1) ≥ 4-point reduction in the SLEDAI-2K total score; 2) no new severe disease activity (BILAG A organ score) or more than 1 new moderate organ score (BILAG B) compared with baseline; and 3) no deterioration from baseline in the PGA by ≥ 30 millimeters. The SLEDAI-2K total score falls between 0 and 105, with higher scores representing increased disease activity. The SRI-4 response in subjects with moderate to severe SLE is associated with broad improvements in clinical and subject-reported outcomes.

End point type

Primary

End point timeframe

Day 210

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the primary endpoint for Phase 2 only

End point values	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Number of subjects analysed	37	75
Units: Subjects
number (not applicable)
SRI-4 Response	19	40
≥ 4-Point Reduction from Baseline SLEDAI-2K score	19	40
No New BILAG A or More than One BILAG B OrganScore	27	68
No Deterioration from Baseline in PGA by >=30mm	27	68

Statistical Analysis 1

Statistical analysis description

Statistical Analysis: SRI-4 Response

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8434

Method

Pearson’s chi-square test

Parameter type

Observed Difference vs. Placebo

Point estimate

Confidence interval

level

90%

sides

2-sided

lower limit

-14.5

upper limit

18.5

Statistical Analysis 2

Statistical analysis description

Statistical Analysis: >= 4-Point Reduction from Baseline in SLEDAI-2K Global Score

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8434

Method

Pearson’s chi-square test

Parameter type

Observed Difference vs. Placebo

Point estimate

Confidence interval

level

90%

sides

2-sided

lower limit

-14.5

upper limit

18.5

Statistical Analysis 3

Statistical analysis description

Statistical Analysis: No New BILAG A or More than One BILAG B Organ Score Compared with Baseline

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0141

Method

Pearson’s chi-square test

Parameter type

Observed Difference vs. Placebo

Point estimate

17.7

Confidence interval

level

90%

sides

2-sided

lower limit

4.5

upper limit

30.9

Statistical Analysis 4

Statistical analysis description

Statistical Analysis: No Deterioration from Baseline in PGA by >=30mm

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0141

Method

Pearson’s chi-square test

Parameter type

Observed Difference vs. Placebo

Point estimate

17.7

Confidence interval

level

90%

sides

2-sided

lower limit

4.5

upper limit

30.9

Secondary: Phase 1b: Maximum Observed Concentration (Cmax)

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End point title

Phase 1b: Maximum Observed Concentration (Cmax) ^[4]

End point description

The PK of BOS161721 was characterized and the optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in subjects with moderate to severe SLE. n signifies only the subjects with available data for each dose.

End point type

Secondary

End point timeframe

Pre-dose: Days 0, 30, 60, 90, 120, 150, and 180. Post-dose: Days 0, 7, 15, 30, 180, 187, 195, 210, 240, and 270. Post-dose samples were collected at 4, 8, and 24 hours after study drug administration on Days 0, 30, and 180

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 1b only

End point values	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg
Number of subjects analysed	5	9	9
Units: ng/mL
geometric mean (geometric coefficient of variation)
Dose 1 (n=4, 8, 9)	1160 ( 42.0 )	4610 ( 54.8 )	5500 ( 52.3 )
Dose 2 (n=5, 8, 9)	1240 ( 23.9 )	5670 ( 35.7 )	7580 ( 45.1 )
Dose 7 (n=5, 8, 9)	2580 ( 19.1 )	7820 ( 144 )	20300 ( 37.1 )

No statistical analyses for this end point

Secondary: Phase 1b: First Time to Maximum Concentration (Tmax)

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End point title

Phase 1b: First Time to Maximum Concentration (Tmax) ^[5]

End point description

End point type

Secondary

End point timeframe

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 1b only

End point values	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg
Number of subjects analysed	5	9	9
Units: Day
median (full range (min-max))
Dose 1 (n= 4, 8, 9)	7.01 (6.99 to 12.00)	7.00 (5.93 to 15.00)	8.04 (6.95 to 17.04)
Dose 2 (n= 5, 8, 9)	1.04 (1.00 to 29.02)	1.00 (0.99 to 34.97)	1.00 (1.00 to 33.03)
Dose 7 (n= 5, 8, 9)	6.18 (5.03 to 20.04)	3.55 (0.91 to 12.00)	8.96 (1.00 to 28.06)

No statistical analyses for this end point

Secondary: Phase 1b: The Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Quantifiable Concentration (AUClast)

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End point title

Phase 1b: The Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Quantifiable Concentration (AUClast) ^[6]

End point description

End point type

Secondary

End point timeframe

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 1b only

End point values	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg
Number of subjects analysed	5	9	9
Units: day*ng/mL
geometric mean (geometric coefficient of variation)
Dose 1 (n= 4, 8, 9)	25100 ( 40.4 )	89400 ( 51.7 )	124000 ( 40.5 )
Dose 2 (n= 5, 8, 9)	33600 ( 18.2 )	147000 ( 29.7 )	229000 ( 47.9 )
Dose 7 (n= 5, 8, 9)	155000 ( 17.9 )	460000 ( 173 )	1400000 ( 38.7 )

No statistical analyses for this end point

Secondary: Phase 1b: Terminal Elimination Half-life (t1/2)

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End point title

Phase 1b: Terminal Elimination Half-life (t1/2) ^[7]

End point description

End point type

Secondary

End point timeframe

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 1b only

End point values	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg
Number of subjects analysed	5	5	1
Units: Day
geometric mean (geometric coefficient of variation)	75.2 ( 19.9 )	66.3 ( 35.4 )	64.3 ( 999.99 )

No statistical analyses for this end point

Secondary: Phase 1b: Apparent Plasma Clearance After Extravascular Administration (CL/F)

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End point title

Phase 1b: Apparent Plasma Clearance After Extravascular Administration (CL/F) ^[8]

End point description

End point type

Secondary

End point timeframe

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 1b only

End point values	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg
Number of subjects analysed	5	8	9
Units: Liter/day
geometric mean (geometric coefficient of variation)	0.289 ( 18.3 )	0.311 ( 179 )	0.218 ( 38.8 )

No statistical analyses for this end point

Secondary: Phase 1b: Apparent Volume of Distribution After Extravascular Administration (Vz/F)

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End point title

Phase 1b: Apparent Volume of Distribution After Extravascular Administration (Vz/F) ^[9]

End point description

End point type

Secondary

End point timeframe

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 1b only

End point values	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg
Number of subjects analysed	5	5	1
Units: Liter
geometric mean (geometric coefficient of variation)	31.4 ( 33.2 )	18.5 ( 39.6 )	23.0 ( 999.99 )

No statistical analyses for this end point

Secondary: Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3)

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End point title

Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3) ^[10]

End point description

The optimal dose of BOS161721 was selected based on safety, tolerability, PK and pharmacodynamic (PD) effects in subjects with moderate to severe SLE. mean change in % pSTAT3+ Lymphocytes - Stimulated, Day 30: n = 6,5,8,9 mean change in % pSTAT3+ Lymphocytes - Stimulated, Day 44: n = 6,5,8,9 mean change in % pSTAT3+ Lymphocytes -Stimulated, Day 60: n = 6,5,8,9 mean change in % pSTAT3+ Lymphocytes - Stimulated, Day 90: n= 5,5,8,9 Here, n signifies only the subjects with available data for each time point.

End point type

Secondary

End point timeframe

Baseline (Day 0); Days 30, 44, 60, and 90 (pre-dose [trough] samples only)

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 1b only

End point values	Phase 1b: Placebo	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg
Number of subjects analysed	7	5	9	9
Units: Percentage
arithmetic mean (standard deviation)
% pSTAT3+ Lymphocytes - Stimulated, Day 30	12.72 ( 25.172 )	-41.80 ( 24.631 )	-31.35 ( 20.281 )	-25.73 ( 20.895 )
% pSTAT3+ Lymphocytes - Stimulated, Day 44	18.45 ( 24.025 )	-60.00 ( 19.672 )	-32.99 ( 19.899 )	-26.57 ( 20.856 )
% pSTAT3+ Lymphocytes - Stimulated, Day 60	-1.48 ( 19.129 )	-59.46 ( 20.310 )	-32.68 ( 19.214 )	-25.91 ( 20.850 )
% pSTAT3+ Lymphocytes - Stimulated, Day 90	-15.94 ( 34.757 )	-67.48 ( 15.630 )	-33.03 ( 19.637 )	-26.74 ( 20.962 )

No statistical analyses for this end point

Secondary: Phase 1b: Mean Change From Baseline in Compliment 3 (C3) and Compliment (C4) Levels

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End point title

Phase 1b: Mean Change From Baseline in Compliment 3 (C3) and Compliment (C4) Levels ^[11]

End point description

The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in subjects with moderate to severe SLE. n signifies only the subjects with available data for each time point.

End point type

Secondary

End point timeframe

Baseline (Day 0); Days 210

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 1b only

End point values	Phase 1b: Placebo	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg
Number of subjects analysed	7	5	9	9
Units: gram/Litre
arithmetic mean (standard deviation)
C3, Day 210 (n=5,5,8,9)	0.094 ( 0.2289 )	-0.032 ( 0.0876 )	0.050 ( 0.3424 )	-0.078 ( 0.2879 )
C4, Day 210 (n=5,5,8,9)	0.024 ( 0.0391 )	-0.038 ( 0.0370 )	-0.007 ( 0.0783 )	-0.024 ( 0.0410 )

No statistical analyses for this end point

Secondary: Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype

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End point title

Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype ^[12]

End point description

The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in subjects with moderate to severe SLE.

End point type

Secondary

End point timeframe

Baseline (Day 0); Day 180

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 1b only

End point values	Phase 1b: Placebo	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg
Number of subjects analysed	7	5	9	9
Units: Change
arithmetic mean (standard deviation)
CD19+% of CD45+ Lymphocytes	-2.07 ( 3.201 )	-5.34 ( 4.663 )	-0.39 ( 4.201 )	0.27 ( 3.481 )
CD25+CD127-% of CD4+CD8-	-1.03 ( 1.388 )	-0.22 ( 2.406 )	-0.38 ( 1.495 )	-1.08 ( 2.266 )
CD4+CD8-% of CD3+	-1.01 ( 10.866 )	-3.08 ( 5.272 )	0.88 ( 7.434 )	-5.04 ( 7.671 )
CD56+% OF CD45+ Lymphocytes	-0.56 ( 2.093 )	-5.76 ( 4.231 )	-2.38 ( 2.461 )	2.04 ( 7.984 )
CD8+CD4-% of CD3+	-3.00 ( 7.792 )	-1.38 ( 4.467 )	-2.92 ( 5.010 )	-0.24 ( 6.517 )
CXCR5+% of CD25+CD127-	0.20 ( 4.676 )	7.02 ( 3.371 )	10.62 ( 11.963 )	0.63 ( 5.915 )
CXCR5+% of CD4+CD8-	0.81 ( 12.373 )	15.18 ( 7.564 )	13.14 ( 16.091 )	-0.69 ( 7.208 )
ICOS+% of CD25+CD127-	8.59 ( 10.618 )	1.56 ( 3.840 )	12.93 ( 11.905 )	4.27 ( 17.059 )
ICOS+% of CD4+CD8-	3.93 ( 6.906 )	0.14 ( 5.227 )	5.01 ( 5.053 )	0.54 ( 15.534 )
IgD+C27-% of CD19+	0.20 ( 7.127 )	2.42 ( 5.882 )	-1.07 ( 4.748 )	-0.80 ( 6.031 )
IgD+CD27+% of CD19+	1.29 ( 1.785 )	-3.24 ( 6.080 )	-1.24 ( 2.823 )	1.00 ( 3.260 )
IgD+CD27-CD38++CD24++% of CD19+	0.50 ( 1.262 )	0.56 ( 1.688 )	-0.42 ( 2.351 )	0.16 ( 1.385 )
IgD-CD27+% of CD19+	-0.21 ( 3.866 )	-0.48 ( 3.891 )	2.02 ( 3.751 )	0.70 ( 3.740 )
IgD-CD27+CD38++CD138+% of CD19+	0.03 ( 0.049 )	0.04 ( 0.089 )	0.08 ( 0.172 )	-0.02 ( 0.130 )
IgD-CD27+CD38++CD138-% of CD19+	-0.20 ( 0.432 )	-0.20 ( 0.354 )	0.59 ( 1.437 )	-0.63 ( 1.081 )
IgD-CD27-% of CD19+	-1.29 ( 2.963 )	1.36 ( 2.373 )	0.32 ( 2.059 )	-0.83 ( 1.648 )
PD-1+% of CD25+CD127-	0.31 ( 6.093 )	3.30 ( 5.039 )	7.41 ( 6.064 )	-8.49 ( 13.258 )
PD-1+% of CD4+CD8-	-0.07 ( 6.366 )	4.14 ( 4.146 )	6.39 ( 5.882 )	-9.01 ( 13.036 )

No statistical analyses for this end point

Secondary: Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit

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End point title

Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit ^[13]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 0); Days 30, 60, 90, 120, 150, 180, 210, 240, and 270

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 1b only

End point values	Phase 1b: Placebo	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg
Number of subjects analysed	7	5	9	9
Units: International units per millilitre
arithmetic mean (standard deviation)
Day 30 (n= 7,5,8,9)	-1.11 ( 3.504 )	0.48 ( 0.410 )	5.34 ( 9.053 )	-11.51 ( 32.444 )
Day 60 (n=7,5,8,9)	-1.81 ( 5.048 )	0.40 ( 0.376 )	8.06 ( 18.430 )	-6.11 ( 15.612 )
Day 90 (n=6,5,8,9)	0.15 ( 0.448 )	0.00 ( 0.187 )	19.31 ( 48.594 )	-13.44 ( 35.152 )
Day 120 (n=6,5,8,9)	-0.02 ( 0.270 )	0.41 ( 0.598 )	12.30 ( 35.583 )	-15.58 ( 47.248 )
Day 150 (n=5,5,8,9)	-0.03 ( 0.199 )	0.62 ( 0.709 )	17.39 ( 50.086 )	-11.18 ( 38.152 )
Day 180 (n=7,5,9,9)	-2.13 ( 5.905 )	0.52 ( 0.584 )	8.00 ( 21.169 )	-17.13 ( 49.897 )
Day 210 (n=5,5,8,9)	0.05 ( 0.359 )	0.07 ( 0.540 )	6.76 ( 20.173 )	-17.96 ( 50.274 )
Day 240 (n=5,5,8,9)	0.07 ( 0.428 )	0.34 ( 1.117 )	6.81 ( 21.903 )	-18.35 ( 47.898 )
Day 270 (n=7,5,8,9)	-1.94 ( 4.974 )	0.37 ( 0.700 )	7.99 ( 24.116 )	-9.71 ( 27.833 )

No statistical analyses for this end point

Secondary: Phase 1b: Mean change From Baseline in Anti-Sjögren syndrome A and B (SSA, SSB)

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End point title

Phase 1b: Mean change From Baseline in Anti-Sjögren syndrome A and B (SSA, SSB) ^[14]

End point description

The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in subjects with moderate to severe SLE.

End point type

Secondary

End point timeframe

Baseline (Day 0); Day 180

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 1b only

End point values	Phase 1b: Placebo	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg
Number of subjects analysed	7	5	9	9
Units: U/mL
arithmetic mean (standard deviation)
La Antibody	0.04 ( 0.175 )	0.11 ( 0.108 )	1.02 ( 2.639 )	0.47 ( 1.668 )
Sjogrens SS-A52 Antibody	-0.04 ( 0.128 )	0.05 ( 0.112 )	0.19 ( 0.567 )	-2.25 ( 4.861 )
Sjogrens SS-A60 Antibody	0.00 ( 0.000 )	0.00 ( 0.000 )	-2.62 ( 7.867 )	-4.36 ( 8.684 )

No statistical analyses for this end point

Secondary: Phase 1b: Mean change From Baseline in Anti-Smith antibody (Sm)

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End point title

Phase 1b: Mean change From Baseline in Anti-Smith antibody (Sm) ^[15]

End point description

The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in subjects with moderate to severe SLE.

End point type

Secondary

End point timeframe

Baseline (Day 0); Day 180

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 1b only

End point values	Phase 1b: Placebo	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg
Number of subjects analysed	7	5	9	9
Units: U/mL
arithmetic mean (standard deviation)	-1.87 ( 4.827 )	0.74 ( 0.391 )	-3.21 ( 9.419 )	3.61 ( 19.504 )

No statistical analyses for this end point

Secondary: Phase 1b: Mean Change From Baseline in Antiphospholipid (APL) autoantibodies (Beta 2 glycoprotein, cardiolipin IgG)

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End point title

Phase 1b: Mean Change From Baseline in Antiphospholipid (APL) autoantibodies (Beta 2 glycoprotein, cardiolipin IgG) ^[16]

End point description

The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in subjects with moderate to severe SLE.

End point type

Secondary

End point timeframe

Baseline (Day 0); Day 180

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 1b only

End point values	Phase 1b: Placebo	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg
Number of subjects analysed	7	5	9	9
Units: U/mL
arithmetic mean (standard deviation)
Anti-Cardiolipin IgG Antibody	-0.03 ( 0.412 )	3.55 ( 5.559 )	0.07 ( 0.585 )	-0.42 ( 0.180 )
Beta-2 Glycoprotein 1 IgG Antibody	-0.11 ( 0.358 )	-7.48 ( 23.684 )	-0.14 ( 0.882 )	0.02 ( 0.787 )

No statistical analyses for this end point

Secondary: Phase 1b: Mean Change From Baseline in Abrogation of IL-21 Gene Signature

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End point title

Phase 1b: Mean Change From Baseline in Abrogation of IL-21 Gene Signature ^[17]

End point description

The optimal dose of BOS161721 was selected based on safety, tolerability, PK and PD data in subjects with moderate to severe SLE. 99.999 = Data were not analyzed for this endpoint

End point type

Secondary

End point timeframe

Baseline (Day 0); Days 15, 90, 180, and 270

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 1b only

End point values	Phase 1b: Placebo	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg
Number of subjects analysed	7	5	9	9
Units: Percentage
arithmetic mean (standard deviation)	99.999 ( 99.999 )	99.999 ( 99.999 )	99.999 ( 99.999 )	99.999 ( 99.999 )

No statistical analyses for this end point

Secondary: Phase 2: Number of Subjects With an SRI-4, SRI-5, and SRI-6 Response at Each Visit

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End point title

Phase 2: Number of Subjects With an SRI-4, SRI-5, and SRI-6 Response at Each Visit ^[18]

End point description

The SRI-4 is a composite index of SLE disease improvement that consists of scores derived from the SLE Disease Activity Index 2000 (SLEDAI-2K) and the British Isles Lupus Assessment Group (BILAG) 2004 Index. Response based on the SRI-4 is defined by: 1) ≥ 4-point reduction in the SLEDAI-2K global score; 2) no new severe disease activity (BILAG A organ score) or more than 1 new moderate organ score (BILAG B); and 3) no deterioration from baseline in the Physician's Global Assessment (PGA) by ≥ 30 millimeters. The SRI-4 response in subjects with moderate to severe SLE is associated with broad improvements in clinical and subject-reported outcomes. SRI-5 and SRI-6 are composite indices of SLE disease improvement that consist of scores derived from the SLEDAI-2K and the BILAG 2004 Index. The SRI-5 and SRI-6 are computed with a minimal five-point or six-point improvement in SLEDAI-2K being required, respectively. n signifies only the subjects with available data for each time point.

End point type

Secondary

End point timeframe

Days 30, 60, 90, 120, 150, 180, 210, 240, and 270

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 2 only

End point values	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Number of subjects analysed	37	75
Units: Subjects
number (not applicable)
SRI-4, Day 30 (n=36, 73)	5	0
SRI-4, Day 60 (n=35, 71)	11	15
SRI-4, Day 90 (n= 35, 65)	15	24
SRI-4, Day 120 (n=35, 66)	17	29
SRI-4, Day 150 (n=35, 71)	19	35
SRI-4, Day 180 (n=35, 72)	20	37
SRI-4, Day 210 (n=37, 75)	19	40
SRI-5, Day 30 (n= 36, 73)	2	0
SRI-5, Day 60 (n=35, 71)	1	10
SRI-5, Day 90 (n= 35, 65)	3	15
SRI-5, Day 120 (n= 35, 66)	8	15
SRI-5, Day 150 (n= 35, 71)	15	22
SRI-5, Day 180 (n= 35, 72)	14	29
SRI-5, Day 210 (n= 37, 75)	17	29
SRI-6, Day 30 (n= 36, 73)	1	0
SRI-6, Day 60 (n= 35, 71)	1	10
SRI-6, Day 90 (n=35, 65)	3	15
SRI-6, Day 120 (n= 35, 66)	8	14
SRI-6, Day 150 (n= 35, 71)	15	22
SRI-6, Day 180 (n= 35, 72)	14	28
SRI-6, Day 210 (n= 37, 75)	17	29

No statistical analyses for this end point

Secondary: Phase 2: Number of Subjects With a Sustained Reduction From Baseline of Oral Corticosteroid (CS) (≤ 7.5 mg/Day and < Day 0 Dose) Between Day 150 and Day 210

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End point title

Phase 2: Number of Subjects With a Sustained Reduction From Baseline of Oral Corticosteroid (CS) (≤ 7.5 mg/Day and < Day 0 Dose) Between Day 150 and Day 210 ^[19]

End point description

Effect of BOS161721 compared with placebo for response on clinical indicators of SLE activity was assessed in adult subjects with moderate to severe SLE on limited background standard of care treatment. Here subjects analysed signifies only the number of subjects taking oral corticosteroids at baseline.

End point type

Secondary

End point timeframe

Day 150 to Day 210

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 2 only

End point values	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Number of subjects analysed	25	67
Units: Subjects
number (not applicable)	7	17

Statistical Analysis 1

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7985

Method

Pearson’s chi-square test

Parameter type

Observed Difference vs. Placebo

Point estimate

-2.6

Confidence interval

level

90%

sides

2-sided

lower limit

-19.8

upper limit

14.5

Secondary: Phase 2: Number of Subjects With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210

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End point title

Phase 2: Number of Subjects With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210 ^[20]

End point description

The BILAG-2004 index is an organ-specific 97-question assessment based on the principle of the doctor's intent to treat. Only clinical features attributable to SLE disease activity were recorded and based on the subject's condition in the last 4 weeks compared with the previous 4 weeks. It was scored as not present (0), improved (1), the same (2), worse (3), or new (4). Disease activity was graded separately for 9 body systems to 5 different grades (A to E) as follows: A is very active disease, B is moderate activity, C is mild stable disease, D is inactive now but previously active, and E indicates the organ was never involved. A shift from BILAG-2004 Grade A or B to a lower grade indicates a clinically relevant change in disease activity as the BILAG-2004 grades mirror the decision points for treatment interventions. n signifies only the subjects with available data for each time point.

End point type

Secondary

End point timeframe

Days 30, 60, 90, 120, 150, 180, 210

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 2 only

End point values	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Number of subjects analysed	37	75
Units: Subjects
number (not applicable)
Overall (n=37, 75)	6	7
Day 30 (n = 36, 73)	1	2
Day 60 (n= 33, 66)	0	0
Day 90 (n= 33, 65)	2	0
Day 120 (n = 31, 65)	1	0
Day 150 (n = 32, 71)	0	1
Day 180 (n= 34, 71)	1	3
Day 210 (n = 31, 72)	0	1

Statistical Analysis 1

Statistical analysis description

Statistical Analysis 1 for Overall

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3498

Method

Pearson’s chi-square test

Parameter type

Observed Difference vs. Placebo

Point estimate

-6.9

Confidence interval

level

90%

sides

2-sided

lower limit

-22.9

upper limit

9.8

Secondary: Phase 2: Number of Subjects With Physician’s Global Assessment (PGA) Worsening

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End point title

Phase 2: Number of Subjects With Physician’s Global Assessment (PGA) Worsening ^[21]

End point description

The PGA is used to assess Investigator's general impression on the patient's overall status of SLE disease activity via visual analogue scale (100 mm) with 0 being "very good, asymptomatic and no limitation of normal activities" with 100 mm being "most severe possible disease ever seen in all SLE patients". PGA worsening is defined as an increase of ≥ 30 mm from baseline.

End point type

Secondary

End point timeframe

Days 30, 60, 90, 120, 150, 180, and 210

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 2 only

End point values	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Number of subjects analysed	37	75
Units: Subjects
number (not applicable)
Overall	13	10
Day 210	10	7

Statistical Analysis 1

Statistical analysis description

Statistical analysis for Overall

Comparison groups

Phase 2: Placebo v Phase 2: BOS161721 120 mg

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0072

Method

Pearson’s chi-square test

Parameter type

Observed Difference vs. Placebo

Point estimate

-21.8

Confidence interval

level

90%

sides

2-sided

lower limit

-36.2

upper limit

-7.4

Statistical Analysis 2

Statistical analysis description

Statistical Analysis for Day 210

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0141

Method

Pearson’s chi-square test

Parameter type

Observed Difference vs. Placebo

Point estimate

-17.7

Confidence interval

level

90%

sides

2-sided

lower limit

-30.9

upper limit

-4.5

Secondary: Phase 2: Number of Subjects With a BILAG-based Composite Lupus Assessment (BICLA) Response at Day 210

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End point title

Phase 2: Number of Subjects With a BILAG-based Composite Lupus Assessment (BICLA) Response at Day 210 ^[22]

End point description

The BICLA is a responder index developed to measure response to therapy, and it includes scores from the BILAG, SLEDAI-2K, and Physician's Global Assessment (PGA). BICLA response is defined as: 1) at least 1 gradation of improvement in baseline BILAG 2004 scores in all body systems with moderate disease activity at entry (eg, all B [moderate disease] scores falling to C [mild], or D [no activity]); 2) no new BILAG A or more than 1 new BILAG B scores; 3) no worsening of total SLEDAI-2K score from baseline; 4) ≤ 10% deterioration in PGA score; and 5) no treatment failure. The PGA is measured on a 0 to 100 mm scale with score 0 to be No Disease Activity and score 100 to be the most Severe Disease Activity.

End point type

Secondary

End point timeframe

Day 210

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 2 only

End point values	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Number of subjects analysed	37	75
Units: Subjects
number (not applicable)	12	28

Statistical Analysis 1

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6107

Method

Pearson’s chi-square test

Parameter type

Observed Difference vs. Placebo

Point estimate

4.9

Confidence interval

level

90%

sides

2-sided

lower limit

-10.7

upper limit

20.5

Secondary: Phase 2: Number of Subjects With a Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Response at Day 210

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End point title

Phase 2: Number of Subjects With a Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Response at Day 210 ^[23]

End point description

The CLASI is a comprehensive tool for assessment of disease activity (CLASI-A) in cutaneous lupus, shown to be valid, reliable, and sensitive to changes in disease activity. Response is defined as at least 50% improvement from baseline in "A" scores. This assessment was applied to all subjects as all were required to have cutaneous disease activity. The total score represents the sum of the individual scores and ranges from 0 to 70. Higher scores are awarded for more severe manifestations.

End point type

Secondary

End point timeframe

Day 210

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 2 only

End point values	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Number of subjects analysed	37	75
Units: Subjects
number (not applicable)	16	44

Statistical Analysis 1

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1237

Method

Pearson’s chi-square test

Parameter type

Observed Difference vs. Placebo

Point estimate

15.4

Confidence interval

level

90%

sides

2-sided

lower limit

-0.9

upper limit

31.8

Secondary: Phase 2: Number of Subjects With Medication Failures

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End point title

Phase 2: Number of Subjects With Medication Failures ^[24]

End point description

Effect of BOS161721 compared with placebo for response on clinical indicators of SLE activity was assessed in adult subjects with moderate to severe SLE on limited background standard of care treatment. n signifies the number of subjects evaluable at any time (overall assessment) or at the given timepoint (by visit assessment).

End point type

Secondary

End point timeframe

Days 30, 60, 90, 120, 150, 180, and 210

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 2 only

End point values	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Number of subjects analysed	37	75
Units: Subjects
number (not applicable)
Overall (n=37, 75)	9	8
Day 210 (n= 33, 72)	7	5

Statistical Analysis 1

Statistical analysis description

Statistical Analysis for Overall

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0581

Method

Pearson’s chi-square test

Parameter type

Observed Difference vs. Placebo

Point estimate

-13.7

Confidence interval

level

90%

sides

2-sided

lower limit

-26.7

upper limit

-0.7

Statistical Analysis 2

Statistical analysis description

Statistical Analysis for Day 210

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0471

Method

Pearson’s chi-square test

Parameter type

Observed Difference vs. Placebo

Point estimate

-14.3

Confidence interval

level

90%

sides

2-sided

lower limit

-31.2

upper limit

3.2

Secondary: Phase 2: Mean Change From Baseline in CLASI at Day 210

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End point title

Phase 2: Mean Change From Baseline in CLASI at Day 210 ^[25]

End point description

The CLASI is a comprehensive tool for the assessment of disease activity (CLASI-A) and damage (CLASI-B) in cutaneous lupus, shown to be valid, reliable, and sensitive to changes in disease activity. Response is defined as 50% improvement from baseline in "A" or "B" scores. This assessment was applied to all subjects as all were required to have cutaneous disease activity. The total score represents the sum of the individual scores and ranges from 0 to 70 (CLASI-A) and 0 to 58 (CLASI-B). Higher scores are awarded for more severe manifestations. Change from baseline was calculated as the post-baseline value minus the baseline value.

End point type

Secondary

End point timeframe

Baseline, Day 210

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 2 only

End point values	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Number of subjects analysed	37	75
Units: Score on a scale
arithmetic mean (standard deviation)
CLASI-A (Total Activity)	-4.8 ( 4.08 )	-5.2 ( 4.62 )
CLASI-B (Total Damage)	-0.6 ( 2.61 )	-0.2 ( 0.90 )

Statistical Analysis 1

Statistical analysis description

Statistical Analysis for CLASI-A (Total Activity)

Comparison groups

Phase 2: Placebo v Phase 2: BOS161721 120 mg

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority ^[26]

P-value

= 0.6596

Method

ANCOVA

Parameter type

Treatment Difference (BOS161721-Placebo)

Point estimate

-0.3

Confidence interval

level

90%

sides

2-sided

lower limit

-1.63

upper limit

0.94

Variability estimate

Standard error of the mean

Dispersion value

0.78

Notes
[26] - This is based on LS Means

Statistical Analysis 2

Statistical analysis description

Statistical Analysis for CLASI-B (Total Damage)

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority ^[27]

P-value

= 0.4105

Method

ANCOVA

Parameter type

Treatment Difference (BOS161721-Placebo)

Point estimate

0.3

Confidence interval

level

90%

sides

2-sided

lower limit

-0.27

upper limit

0.81

Variability estimate

Standard error of the mean

Dispersion value

0.33

Notes
[27] - This is based on LS Means

Secondary: Phase 2: Mean Change From Baseline in PGA

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End point title

Phase 2: Mean Change From Baseline in PGA ^[28]

End point description

End point type

Secondary

End point timeframe

Baseline, Day 210

Notes
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 2 only

End point values	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Number of subjects analysed	37	75
Units: Score on a scale
arithmetic mean (standard deviation)	-29.2 ( 20.69 )	-28.7 ( 20.35 )

Statistical Analysis 1

Statistical analysis description

Statistical Analysis for Day 210

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority ^[29]

P-value

= 0.8546

Method

ANCOVA

Parameter type

Treatment Difference (BOS161721-Placebo)

Point estimate

0.8

Confidence interval

level

90%

sides

2-sided

lower limit

-6.07

upper limit

7.58

Variability estimate

Standard error of the mean

Dispersion value

4.11

Notes
[29] - This is based on LS Means

Secondary: Phase 2: Mean Change From Baseline in the Total Number of Swollen Joints, Tender Joints, and Active Joints (Swelling and Tenderness in the Same Joint) in the American College of Rheumatology-28 (ACR-28) Joint Count

Top of page

End point title

Phase 2: Mean Change From Baseline in the Total Number of Swollen Joints, Tender Joints, and Active Joints (Swelling and Tenderness in the Same Joint) in the American College of Rheumatology-28 (ACR-28) Joint Count ^[30]

End point description

The ACR-28 joint count evaluated the number of tender and swollen joints in the shoulder, elbow, wrist, hand, and knee joints. Joints of the feet were excluded. Change from baseline was calculated as the post-baseline value minus the baseline value.

End point type

Secondary

End point timeframe

Baseline, Day 210

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 2 only

End point values	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Number of subjects analysed	37	75
Units: Number of swollen/tender/active joints
arithmetic mean (standard deviation)
Sum of Swelling	-6.8 ( 5.17 )	-5.9 ( 5.05 )
Sum of Tenderness	-8.3 ( 7.00 )	-7.2 ( 5.57 )
Sum of Active Joints	-6.5 ( 5.54 )	-5.6 ( 4.65 )

Statistical Analysis 1

Statistical analysis description

Statistical Analysis for Sum of Swelling for Day 210

Comparison groups

Phase 2: Placebo v Phase 2: BOS161721 120 mg

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority ^[31]

P-value

= 0.4455

Method

ANCOVA

Parameter type

Treatment Difference (BOS161721-Placebo)

Point estimate

0.5

Confidence interval

level

90%

sides

2-sided

lower limit

-0.63

upper limit

1.71

Variability estimate

Standard error of the mean

Dispersion value

0.7

Notes
[31] - This is based on LS Means

Statistical Analysis 2

Statistical analysis description

Statistical Analysis for Sum of Tenderness for Day 210

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority ^[32]

P-value

= 0.3367

Method

ANCOVA

Parameter type

Treatment Difference (BOS161721-Placebo)

Point estimate

0.9

Confidence interval

level

90%

sides

2-sided

lower limit

-0.65

upper limit

2.47

Variability estimate

Standard error of the mean

Dispersion value

0.94

Notes
[32] - This is based on LS Means

Statistical Analysis 3

Statistical analysis description

Statistical Analysis for Sum of Active Joints for Day 210

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority ^[33]

P-value

= 0.255

Method

ANCOVA

Parameter type

Treatment Difference (BOS161721-Placebo)

Point estimate

0.8

Confidence interval

level

90%

sides

2-sided

lower limit

-0.34

upper limit

1.86

Variability estimate

Standard error of the mean

Dispersion value

0.66

Notes
[33] - This is based on LS Means

Secondary: Phase 2: Mean Change From Baseline in SLEDAI-2K at Day 210

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End point title

Phase 2: Mean Change From Baseline in SLEDAI-2K at Day 210 ^[34]

End point description

The SLEDAI-2K is a validated instrument that measures disease activity in SLE subjects at the time of the visit and in the previous 30 days. It is a global index and includes 24 clinical and laboratory variables that are weighted by the type of manifestation, but not by severity. The total score falls between 0 and 105, with higher scores representing increased disease activity. A SLEDAI -2K of 6 or more generally represents moderately to severely active disease. Change from baseline was calculated as the post-baseline value minus the baseline value.

End point type

Secondary

End point timeframe

Baseline, Day 210

Notes
[34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 2 only

End point values	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Number of subjects analysed	37	75
Units: Score on a scale
arithmetic mean (standard deviation)	-4.7 ( 3.71 )	-3.9 ( 3.31 )

Statistical Analysis 1

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority ^[35]

P-value

= 0.2498

Method

ANCOVA

Parameter type

Treatment Difference (BOS161721-Placebo)

Point estimate

0.8

Confidence interval

level

90%

sides

2-sided

lower limit

-0.34

upper limit

1.93

Variability estimate

Standard error of the mean

Dispersion value

0.68

Notes
[35] - This is based on LS Means

Secondary: Phase 2: Mean Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index

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End point title

Phase 2: Mean Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index ^[36]

End point description

The SLICC/ACR damage index is a validated instrument to assess damage, defined as irreversible impairment, continuously persistent for 6 months (ascertained by clinical assessment), occurring since the onset of lupus, and it is based on a weighted scoring system. This index records damage occurring in subjects with SLE regardless of cause, with demonstrated content, face, criterion, and discriminant validity. A score of 0=no damage. Total maximum score is 47 and increasing score indicates increasing disease severity. Here, subjects analysed signifies only the subjects with available data for the end point.

End point type

Secondary

End point timeframe

Baseline; Day 180

Notes
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 2 only

End point values	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Number of subjects analysed	30	67
Units: Score on a scale
arithmetic mean (standard deviation)	0 ( 0 )	0.1 ( 0.24 )

Statistical Analysis 1

Statistical analysis description

Statistical Analysis for Day 180

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[37]

P-value

= 0.2558

Method

ANCOVA

Parameter type

Treatment Difference (BOS161721-Placebo)

Point estimate

Confidence interval

level

90%

sides

2-sided

lower limit

-0.02

upper limit

0.12

Variability estimate

Standard error of the mean

Dispersion value

0.04

Notes
[37] - This is based on LS Means

Secondary: Phase 2: Time to Medication Failure

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End point title

Phase 2: Time to Medication Failure ^[38]

End point description

Subjects who received prohibited medications or undergo unallowable corticosteroid (CS) usage were considered "medication failures". 999.999 = Median was not established based on the number of medication failures observed.

End point type

Secondary

End point timeframe

Up to Day 270

Notes
[38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 2 only

End point values	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Number of subjects analysed	37	75
Units: Days
median (confidence interval 90%)	999.999 (999.999 to 999.999)	999.999 (999.999 to 999.999)

Statistical Analysis 1

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority ^[39]

P-value

= 0.0479

Method

Log Rank

Parameter type

Hazard ratio (HR)

Point estimate

0.39

Confidence interval

level

90%

sides

2-sided

lower limit

0.18

upper limit

0.88

Notes
[39] - Hazard rate of BOS161721 120 mg / Hazard rate of placebo

Secondary: Mean Percent Change in CS Administration From the Baseline Day 0 Dose Through Day 210 in Subjects Receiving ≥ 7.5 mg/Day Prednisone Equivalent at Day 0

Top of page

End point title

Mean Percent Change in CS Administration From the Baseline Day 0 Dose Through Day 210 in Subjects Receiving ≥ 7.5 mg/Day Prednisone Equivalent at Day 0 ^[40]

End point description

The percent reduction in CS administration from Day 0 through Day 210 was determined based on the average daily CS usage. Here, subjects analysed signifies only the subjects with available data for the end point.

End point type

Secondary

End point timeframe

Baseline; Day 210

Notes
[40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 2 only

End point values	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Number of subjects analysed	13	45
Units: Percent Reduction in Dose (mg/day)
arithmetic mean (standard deviation)	-36.61 ( 22.389 )	-21.49 ( 26.950 )

No statistical analyses for this end point

Secondary: Phase 2: Duration of Longest SRI-4 Response

Top of page

End point title

Phase 2: Duration of Longest SRI-4 Response ^[41]

End point description

The SRI-4 is a composite index of SLE disease improvement that consists of scores derived from SLEDAI-2K, BILAG 2004 Index and PGA. Response based on the SRI-4 is defined by: 1) ≥ 4-point reduction in the SLEDAI-2K total score; 2) no new severe disease activity (BILAG A organ score) or more than 1 new moderate organ score (BILAG B) compare with baseline; and 3) no deterioration from baseline in the PGA by ≥ 30 millimeters. The total SLEDAI-2K score falls between 0 and 105, with higher scores representing increased disease activity. The PGA is used to assess Investigator's general impression on the patient's overall status of SLE disease activity via visual analogue scale (100 mm) with 0 being "very good, asymptomatic and no limitation of normal activities" with 100 mm being "most severe possible disease ever seen in all SLE patients". The SRI-4 response in subjects with moderate to severe SLE is associated with broad improvements in clinical and subject-reported outcomes.

End point type

Secondary

End point timeframe

Up to Day 270

Notes
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 2 only

End point values	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Number of subjects analysed	37	75
Units: Days
arithmetic mean (standard deviation)	119.8 ( 68.26 )	124.2 ( 68.48 )

Statistical Analysis 1

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority ^[42]

P-value

= 0.7898

Method

ANOVA

Parameter type

Treatment Difference (BOS161721-Placebo)

Point estimate

4.4

Confidence interval

level

90%

sides

2-sided

lower limit

-22.92

upper limit

31.7

Variability estimate

Standard error of the mean

Dispersion value

16.4

Notes
[42] - This is based on LS Means

Secondary: Phase 2: Time to First BILAG Flare (≥ 1 New or Recurrent BILAG A or > 1 New or Recurrent BILAG B) Relative to Baseline Through Day 210

Top of page

End point title

Phase 2: Time to First BILAG Flare (≥ 1 New or Recurrent BILAG A or > 1 New or Recurrent BILAG B) Relative to Baseline Through Day 210 ^[43]

End point description

The BILAG-2004 index is an organ-specific 97-question assessment based on the principle of the doctor's intent to treat. Only clinical features attributable to SLE disease activity were recorded and based on the subject's condition in the last 4 weeks compared with the previous 4 weeks. It was scored as not present (0), improved (1), the same (2), worse (3), or new (4). Disease activity was graded separately for 9 body systems to 5 different grades (A to E) as follows: A is very active disease, B is moderate activity, C is mild stable disease, D is inactive now but previously active, and E indicates the organ was never involved. A shift from BILAG-2004 Grade A or B to a lower grade indicates a clinically relevant change in disease activity as the BILAG-2004 grades mirror the decision points for treatment interventions. 999.999 = Median was not established based on the number of BILAG flares observed.

End point type

Secondary

End point timeframe

Baseline; Day 210

Notes
[43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 2 only

End point values	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Number of subjects analysed	37	75
Units: Days
median (confidence interval 90%)	999.999 (999.999 to 999.999)	999.999 (999.999 to 999.999)

Statistical Analysis 1

Comparison groups

Phase 2: BOS161721 120 mg v Phase 2: Placebo

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority ^[44]

P-value

= 0.0083

Method

Log-Rank Test (2-Sided)

Parameter type

Hazard ratio (HR)

Point estimate

0.33

Confidence interval

level

90%

sides

2-sided

lower limit

0.16

upper limit

0.68

Notes
[44] - Hazard rate of BOS161721 120mg / Hazard rate of placebo

Secondary: Phase 2: Number of Subjects With AEs

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End point title

Phase 2: Number of Subjects With AEs ^[45]

End point description

The safety and tolerability of repeat doses of BOS161721 (120 mg) administered SC were assessed in adult subjects with moderate to severe SLE on limited background standard of care treatment.

End point type

Secondary

End point timeframe

Up to Day 270

Notes
[45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is the secondary endpoint for Phase 2 only

End point values	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Number of subjects analysed	37	76
Units: Subjects
number (not applicable)
Any TEAE	23	44
Related TEAE	4	8
Serious TEAE	3	2
Related Serious TEAE	0	0
Any CTCAE Grade 2 or Higher TEAE	16	25
Any Related CTCAE Grade 2 or Higher TEAE	0	3
Any CTCAE Grade 3 TEAE	3	6
Any Related CTCAE Grade 3 or Higher TEAE	0	0
Any CTCAE Grade 4 TEAE	0	0
Any Related CTCAE Grade 4 TEAE	0	0
TEAE Leading to Discontinuation of Study Treatment	1	0
Related TEAE Leading to Discont of Study Treatment	0	0
TEAE of Special Interest	0	1
Related TEAE of Special Interest	0	0
Dose-Limiting Toxicity	0	0
Related Dose-Limiting Toxicity	0	0
TEAE Resulting in Death	0	0
Related TEAE Resulting in Death	0	0
Injection Site Reaction	1	1

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Up to Day 270

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

23.1

Reporting group title

Phase 1b: Placebo

Reporting group description

Reporting group title

Phase 1b: Cohort 1: BOS161721 20 mg

Reporting group description

Reporting group title

Phase 1b: Cohort 2: BOS161721 60 mg

Reporting group description

subjects were randomized to receive a 60 mg SC dose of BOS161721. Subjects received a total of 7 SC monthly doses of BOS161721 on Days 0, 30, 60, 90, 120, 150, and 180, followed by safety follow-up visits on at Days 210, 240, and 270

Reporting group title

Phase 1b: Cohort 3: BOS161721 120 mg

Reporting group description

Reporting group title

Phase 2: Placebo

Reporting group description

Reporting group title

Phase 2: BOS161721 120 mg

Reporting group description

Serious adverse events	Phase 1b: Placebo	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 7 (14.29%)	0 / 5 (0.00%)	2 / 9 (22.22%)	0 / 9 (0.00%)	3 / 37 (8.11%)	2 / 76 (2.63%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intraductal proliferative breast lesion
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 37 (0.00%)	1 / 76 (1.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of skin
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Exomphalos
subjects affected / exposed	1 / 7 (14.29%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 37 (2.70%)	0 / 76 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 37 (2.70%)	0 / 76 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 37 (2.70%)	0 / 76 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lupus pneumonitis
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 37 (2.70%)	0 / 76 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Biliary colic
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 37 (2.70%)	0 / 76 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pyelonephritis acute
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 37 (0.00%)	1 / 76 (1.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Phase 1b: Placebo	Phase 1b: Cohort 1: BOS161721 20 mg	Phase 1b: Cohort 2: BOS161721 60 mg	Phase 1b: Cohort 3: BOS161721 120 mg	Phase 2: Placebo	Phase 2: BOS161721 120 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	4 / 7 (57.14%)	2 / 5 (40.00%)	7 / 9 (77.78%)	8 / 9 (88.89%)	22 / 37 (59.46%)	44 / 76 (57.89%)
Vascular disorders
Hypertension
subjects affected / exposed	0 / 7 (0.00%)	1 / 5 (20.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	1 / 37 (2.70%)	2 / 76 (2.63%)
occurrences all number	0	1	1	0	1	4
Deep vein thrombosis
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 37 (0.00%)	1 / 76 (1.32%)
occurrences all number	0	0	1	0	0	1
General disorders and administration site conditions
Non-cardiac chest pain
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	2 / 9 (22.22%)	1 / 37 (2.70%)	0 / 76 (0.00%)
occurrences all number	0	0	0	2	1	0
Reproductive system and breast disorders
Menorrhagia
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	2 / 37 (5.41%)	0 / 76 (0.00%)
occurrences all number	0	0	0	0	2	0
Adnexa uteri pain
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	0	2	0	0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	1	0	0	0
Cough
subjects affected / exposed	0 / 7 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	1	0	0	0	0
Pulmonary hypertension
subjects affected / exposed	1 / 7 (14.29%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	1	0	0	0	0	0
Psychiatric disorders
Confusional state
subjects affected / exposed	0 / 7 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	1	0	0	0	0
Depression
subjects affected / exposed	1 / 7 (14.29%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	1	0	0	0	0	0
Insomnia
subjects affected / exposed	0 / 7 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	1	0	0	0	0
Investigations
White blood cells urine positive
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	1 / 37 (2.70%)	2 / 76 (2.63%)
occurrences all number	0	0	2	0	2	5
Blood pressure increased
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 37 (0.00%)	1 / 76 (1.32%)
occurrences all number	0	0	1	0	0	1
Weight increased
subjects affected / exposed	0 / 7 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 37 (2.70%)	0 / 76 (0.00%)
occurrences all number	0	1	0	0	1	0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	1 / 76 (1.32%)
occurrences all number	0	0	0	1	0	1
Animal bite
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	0	1	0	0
Ankle fracture
subjects affected / exposed	1 / 7 (14.29%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	1	0	0	0	0	0
Ligament sprain
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	0	1	0	0
Cardiac disorders
Bundle branch block right
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	1	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	0 / 7 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	2 / 37 (5.41%)	4 / 76 (5.26%)
occurrences all number	0	1	0	0	2	6
Migraine
subjects affected / exposed	1 / 7 (14.29%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	1 / 37 (2.70%)	1 / 76 (1.32%)
occurrences all number	1	0	1	0	1	1
Cervical radiculopathy
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	1	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	2 / 37 (5.41%)	0 / 76 (0.00%)
occurrences all number	0	0	0	0	2	0
Iron deficiency anaemia
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	0	1	0	0
Eye disorders
Cataract
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	1	0	0	0
Diplopia
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	1	0	0	0
Gastrointestinal disorders
Nausea
subjects affected / exposed	1 / 7 (14.29%)	0 / 5 (0.00%)	1 / 9 (11.11%)	2 / 9 (22.22%)	1 / 37 (2.70%)	4 / 76 (5.26%)
occurrences all number	2	0	1	2	2	4
Diarrhoea
subjects affected / exposed	1 / 7 (14.29%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	3 / 37 (8.11%)	1 / 76 (1.32%)
occurrences all number	1	0	0	0	3	1
Constipation
subjects affected / exposed	1 / 7 (14.29%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 37 (2.70%)	2 / 76 (2.63%)
occurrences all number	1	0	0	0	1	2
Vomiting
subjects affected / exposed	1 / 7 (14.29%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	1	0	0	1	0	0
Abdominal pain
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	1	0	0	0
Dental caries
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	0	1	0	0
Dry mouth
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	0	1	0	0
Tongue ulceration
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	1	0	0	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	3 / 37 (8.11%)	2 / 76 (2.63%)
occurrences all number	0	0	0	0	4	2
Arthralgia
subjects affected / exposed	1 / 7 (14.29%)	0 / 5 (0.00%)	1 / 9 (11.11%)	1 / 9 (11.11%)	0 / 37 (0.00%)	1 / 76 (1.32%)
occurrences all number	1	0	1	1	0	1
Bursitis
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	3 / 76 (3.95%)
occurrences all number	0	0	0	1	0	3
Fibromyalgia
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	1 / 76 (1.32%)
occurrences all number	0	0	0	1	0	1
Muscle spasms
subjects affected / exposed	1 / 7 (14.29%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	1	0	0	2	0	0
Pain in extremity
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	1 / 76 (1.32%)
occurrences all number	0	0	0	1	0	1
Sjogren's syndrome
subjects affected / exposed	0 / 7 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 37 (2.70%)	0 / 76 (0.00%)
occurrences all number	0	1	0	0	1	0
Myalgia
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	0	1	0	0
Infections and infestations
Nasopharyngitis
subjects affected / exposed	1 / 7 (14.29%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	3 / 37 (8.11%)	7 / 76 (9.21%)
occurrences all number	1	0	0	0	4	9
Urinary tract infection
subjects affected / exposed	0 / 7 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	4 / 37 (10.81%)	4 / 76 (5.26%)
occurrences all number	0	3	0	0	4	6
Pharyngitis
subjects affected / exposed	0 / 7 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	2 / 37 (5.41%)	4 / 76 (5.26%)
occurrences all number	0	1	0	0	2	4
Upper respiratory tract infection
subjects affected / exposed	1 / 7 (14.29%)	0 / 5 (0.00%)	0 / 9 (0.00%)	2 / 9 (22.22%)	1 / 37 (2.70%)	0 / 76 (0.00%)
occurrences all number	1	0	0	2	1	0
Bronchitis
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	2 / 76 (2.63%)
occurrences all number	0	0	0	1	0	2
Escherichia urinary tract infection
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	2 / 37 (5.41%)	1 / 76 (1.32%)
occurrences all number	0	0	0	0	2	1
Cervicitis
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	1 / 37 (2.70%)	0 / 76 (0.00%)
occurrences all number	0	0	0	1	1	0
Pneumonia
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	1 / 76 (1.32%)
occurrences all number	0	0	0	1	0	1
Vulvovaginal mycotic infection
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 37 (0.00%)	1 / 76 (1.32%)
occurrences all number	0	0	1	0	0	1
Diverticulitis
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	1	0	0	0
Gastroenteritis viral
subjects affected / exposed	1 / 7 (14.29%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	1	0	0	0	0	0
Herpes zoster
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	1	0	0	0
Infected bite
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	0	1	0	0
Nasal abscess
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	1	0	0	0
Otitis media acute
subjects affected / exposed	0 / 7 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	1	0	0	0	0
Sinusitis
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	0	3	0	0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	0 / 76 (0.00%)
occurrences all number	0	0	0	1	0	0
Metabolism and nutrition disorders
Type 2 diabetes mellitus
subjects affected / exposed	0 / 7 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 37 (0.00%)	1 / 76 (1.32%)
occurrences all number	0	0	0	1	0	1

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

08 Nov 2017

Protocol Amendment 1: For clarity, site visits are based on study day number only; Clarification and updated with new safety data; Clarification to correct level of exposure; Removed erroneous text and added clarity that Boston Pharmaceuticals will review data along with DMC for POC Dose selection; Clarification to allow flexibility in exact number enrolled; Dose modifications/ adjustments are not allowed in this study; Screening for POC study can begin while dose decision is being made; Text removed as Boston Pharmaceuticals will be reviewing biomarker data for POC dose selection; Clarification (genotype needed to establish gene signature); text added to clarify how the subject should complete the study; text removed as efficacy data were to be reviewed by Boston Pharmaceuticals in order to make informed dose selection decision.

21 Mar 2018

Protocol Amendment 2: Replaced ‘subjects’ to ‘patients’ since the enrolled participants are with SLE condition; Clarification that POC dose selection will be based on DMC and sponsor assessment; Updated for clarity and to provide a comprehensive list of endpoints identified in the protocol; Clarification on POC sample size; Text updated to clarify that a minimum BILAG 1 ‘A’ or 2 ‘B’ scores is required for screening; Text was added to clarify randomization and blinding process; Clarified that no need for predose injection site reaction assessment at baseline; Text updated to clarify new number of dropouts assumed for the study; Clarify that Grades 2 to 5 injection site reactions are AEs of special interest; Updated to clarify the planned PD assessments; updates done to statistical sections.

27 Jul 2018

Protocol Amendment 3: Text added to clarify that MAD and POC are 2 portions of this 1 study and not 2 separate studies; updates done for Protocol clarification; updates done for statistical clarification; updates done to include more data from the 120 mg cohort in data review to determine POC dose; updates done to inclusion/exclusion criteria; Urine pregnancy test added at day 270 to ensure patient is not pregnant at end of 90 day follow-up due to 41 day half-life of study drug; Added end of study definitions; Added text to ensure eligibility prior to randomization; Added definition of worsening PGA.

23 Jan 2019

Protocol Amendment 4: Changes done to correct the error in the previous version; updates done for protocol clarification; Added text for POC dose and justification; Text added 1) to clarify that basal cell carcinoma is not a neoplasia associated with immune suppression, but rather secondary to sun exposure and 2) to clarify specific opportunistic infections of special interest in this study.

23 Jul 2019

Protocol Amendment 5: Updates done for protocol clarification, Changes done to Objectives and Endpoints; Changes done to Criteria for Inclusion and Exclusion to ensure subjects with moderate to severe active disease are enrolled; provided further clarification that the central eligibility review team can deem a subject in-eligible for randomization even if all entrance criteria are met; Added for opioid dosing in SLE subjects.

30 Apr 2020

Protocol Amendment 6: This amendment summarizes the measures implemented during the COVID-19 pandemic to protect patient safety and data integrity: Safety oversight: In case a subject cannot return to the study site for the scheduled visit, the site staff will contact the subject remotely for safety follow-up; Central Laboratory: In the case that there are courier issues that will prevent the protocol-required laboratory specimens to be sent to the study core laboratory, the site should have the safety laboratory specimens; Investigational Product Dosing: In cases when dosing cannot be performed during the protocol-designated windows, the Investigator should discuss each case with the Sponsor to determine whether it is a missed visit or whether the dosing can be performed outside protocol windows.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Randomized Double-Blind Phase 1b/2 Combined Staggered Multiple Dose Escalation Study of BOS161721 in Systemic Lupus Erythematosus (SLE) Patients on a Background of Limited Standard of Care

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Phase 1b: Number of Subjects With Adverse Events (AEs)

Primary: Phase 1b: Number of Subjects With Adverse Events (AEs)

Primary: Phase 2: Number of Subjects With an SLE Responder Index 4 (SRI-4) Response at Day 210

Primary: Phase 2: Number of Subjects With an SLE Responder Index 4 (SRI-4) Response at Day 210

Secondary: Phase 1b: Maximum Observed Concentration (Cmax)

Secondary: Phase 1b: Maximum Observed Concentration (Cmax)

Secondary: Phase 1b: First Time to Maximum Concentration (Tmax)

Secondary: Phase 1b: First Time to Maximum Concentration (Tmax)

Secondary: Phase 1b: The Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Quantifiable Concentration (AUClast)

Secondary: Phase 1b: The Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Quantifiable Concentration (AUClast)

Secondary: Phase 1b: Terminal Elimination Half-life (t1/2)

Secondary: Phase 1b: Terminal Elimination Half-life (t1/2)

Secondary: Phase 1b: Apparent Plasma Clearance After Extravascular Administration (CL/F)

Secondary: Phase 1b: Apparent Plasma Clearance After Extravascular Administration (CL/F)

Secondary: Phase 1b: Apparent Volume of Distribution After Extravascular Administration (Vz/F)

Secondary: Phase 1b: Apparent Volume of Distribution After Extravascular Administration (Vz/F)

Secondary: Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3)

Secondary: Phase 1b: Mean Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3)

Secondary: Phase 1b: Mean Change From Baseline in Compliment 3 (C3) and Compliment (C4) Levels

Secondary: Phase 1b: Mean Change From Baseline in Compliment 3 (C3) and Compliment (C4) Levels

Secondary: Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype

Secondary: Phase 1b: Mean Change From Baseline in Leukocyte Immunophenotype

Secondary: Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit

Secondary: Phase 1b: Mean Change From Baseline in Anti-double-stranded DNA (dsDNA) Autoantibodies at Each Visit

Secondary: Phase 1b: Mean change From Baseline in Anti-Sjögren syndrome A and B (SSA, SSB)

Secondary: Phase 1b: Mean change From Baseline in Anti-Sjögren syndrome A and B (SSA, SSB)

Secondary: Phase 1b: Mean change From Baseline in Anti-Smith antibody (Sm)

Secondary: Phase 1b: Mean change From Baseline in Anti-Smith antibody (Sm)

Secondary: Phase 1b: Mean Change From Baseline in Antiphospholipid (APL) autoantibodies (Beta 2 glycoprotein, cardiolipin IgG)

Secondary: Phase 1b: Mean Change From Baseline in Antiphospholipid (APL) autoantibodies (Beta 2 glycoprotein, cardiolipin IgG)

Secondary: Phase 1b: Mean Change From Baseline in Abrogation of IL-21 Gene Signature

Secondary: Phase 1b: Mean Change From Baseline in Abrogation of IL-21 Gene Signature

Secondary: Phase 2: Number of Subjects With an SRI-4, SRI-5, and SRI-6 Response at Each Visit

Secondary: Phase 2: Number of Subjects With an SRI-4, SRI-5, and SRI-6 Response at Each Visit

Secondary: Phase 2: Number of Subjects With a Sustained Reduction From Baseline of Oral Corticosteroid (CS) (≤ 7.5 mg/Day and < Day 0 Dose) Between Day 150 and Day 210

Secondary: Phase 2: Number of Subjects With a Sustained Reduction From Baseline of Oral Corticosteroid (CS) (≤ 7.5 mg/Day and < Day 0 Dose) Between Day 150 and Day 210

Secondary: Phase 2: Number of Subjects With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210

Secondary: Phase 2: Number of Subjects With New or Recurrent BILAG Flares (≥ 1 Qualifying BILAG A or > 1 Qualifying BILAG B) Through Day 210

Secondary: Phase 2: Number of Subjects With Physician’s Global Assessment (PGA) Worsening

Secondary: Phase 2: Number of Subjects With Physician’s Global Assessment (PGA) Worsening

Secondary: Phase 2: Number of Subjects With a BILAG-based Composite Lupus Assessment (BICLA) Response at Day 210

Secondary: Phase 2: Number of Subjects With a BILAG-based Composite Lupus Assessment (BICLA) Response at Day 210

Secondary: Phase 2: Number of Subjects With a Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Response at Day 210

Secondary: Phase 2: Number of Subjects With a Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Response at Day 210

Secondary: Phase 2: Number of Subjects With Medication Failures

Secondary: Phase 2: Number of Subjects With Medication Failures

Secondary: Phase 2: Mean Change From Baseline in CLASI at Day 210

Secondary: Phase 2: Mean Change From Baseline in CLASI at Day 210

Secondary: Phase 2: Mean Change From Baseline in PGA

Secondary: Phase 2: Mean Change From Baseline in PGA

Secondary: Phase 2: Mean Change From Baseline in the Total Number of Swollen Joints, Tender Joints, and Active Joints (Swelling and Tenderness in the Same Joint) in the American College of Rheumatology-28 (ACR-28) Joint Count

Secondary: Phase 2: Mean Change From Baseline in the Total Number of Swollen Joints, Tender Joints, and Active Joints (Swelling and Tenderness in the Same Joint) in the American College of Rheumatology-28 (ACR-28) Joint Count

Secondary: Phase 2: Mean Change From Baseline in SLEDAI-2K at Day 210

Secondary: Phase 2: Mean Change From Baseline in SLEDAI-2K at Day 210

Secondary: Phase 2: Mean Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index

Secondary: Phase 2: Mean Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index

Secondary: Phase 2: Time to Medication Failure

Secondary: Phase 2: Time to Medication Failure

Secondary: Mean Percent Change in CS Administration From the Baseline Day 0 Dose Through Day 210 in Subjects Receiving ≥ 7.5 mg/Day Prednisone Equivalent at Day 0

Secondary: Mean Percent Change in CS Administration From the Baseline Day 0 Dose Through Day 210 in Subjects Receiving ≥ 7.5 mg/Day Prednisone Equivalent at Day 0

Secondary: Phase 2: Duration of Longest SRI-4 Response

Secondary: Phase 2: Duration of Longest SRI-4 Response

Secondary: Phase 2: Time to First BILAG Flare (≥ 1 New or Recurrent BILAG A or > 1 New or Recurrent BILAG B) Relative to Baseline Through Day 210

Secondary: Phase 2: Time to First BILAG Flare (≥ 1 New or Recurrent BILAG A or > 1 New or Recurrent BILAG B) Relative to Baseline Through Day 210

Secondary: Phase 2: Number of Subjects With AEs

Secondary: Phase 2: Number of Subjects With AEs

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Clinical Trial Results:
A Randomized Double-Blind Phase 1b/2 Combined Staggered Multiple Dose Escalation Study of BOS161721 in Systemic Lupus Erythematosus (SLE) Patients on a Background of Limited Standard of Care