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Clinical Trial Results:
An open label, two-arm, Phase 2a study to evaluate the effect of rilzabrutinib (PRN1008/SAR444671) on safety and disease activity in participants with IgG4-related disease

Summary
EudraCT number	2022-002959-18
Trial protocol	ES IT
Global end of trial date	15 Oct 2024

Results information
Results version number	v1(current)
This version publication date	29 Oct 2025
First version publication date	29 Oct 2025
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

ACT17125

ISRCTN number

US NCT number

NCT04520451

WHO universal trial number (UTN)

U1111-1260-3972

Sponsor organisation name

Sanofi aventis recherche & développement

Sponsor organisation address

82 Avenue Raspail, Gentilly, France, 94250

Public contact

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com

Scientific contact

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com

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

30 Oct 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

15 Oct 2024

Was the trial ended prematurely?

Main objective of the trial

To evaluate the safety and the efficacy of daily oral administration of rilzabrutinib in participants with immunoglobulin G subclass 4 (IgG4)-related disease (IgG4-RD).

Protection of trial subjects

Participants were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the participant and considering the local culture. During the course of the trial, participants were provided with individual participant cards indicating the nature of the trial the participant is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.

Background therapy

Evidence for comparator

Actual start date of recruitment

22 Aug 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 10

Country: Number of subjects enrolled

France: 1

Country: Number of subjects enrolled

Italy: 1

Country: Number of subjects enrolled

Spain: 2

Country: Number of subjects enrolled

United States: 13

Worldwide total number of subjects

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)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study was conducted at 9 centers in 5 countries. A total of 35 participants were screened between 22 August 2020 and 14 September 2020, of which 8 were screen failures.

Screening details

27 participants were enrolled in the study, of which 13 were in Cohort A and 14 in Cohort B. In Cohort A, 10 participants were randomized to rilzabrutinib treatment group, and 3 participants to Control group. Participants in Cohort B received rilzabrutinib. Note: For Cohort B data collected for first 12 weeks is indicated as Main treatment period.

Period 1 title

Induction Treatment Period (12 Weeks)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Induction Treatment Period: Cohort A (Control)

Arm description

Participants received glucocorticoid minimum starting dose of 20 milligram (mg)/day and the maximum dose of 40 mg/day prednisone equivalent orally for 12 weeks.

Arm type

Active comparator

Investigational medicinal product name

Glucocorticoids

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received minimum starting dose of 20 mg/day and the maximum dose of 40 mg/day prednisone equivalent for 12 weeks.

Induction Treatment Period: Cohort A (Rilzabrutinib)

Arm description

Participants received rilzabrutinib tablets 400 mg orally twice daily (BID) for 12 weeks, along with glucocorticoid minimum starting dose of 20 mg/day and the maximum dose of 40 mg/day prednisone equivalent orally for a maximum of 4 weeks.

Arm type

Experimental

Investigational medicinal product name

Glucocorticoids

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received minimum starting dose of 20 mg/day and the maximum dose of 40 mg/day prednisone equivalent a maximum of 4 weeks.

Investigational medicinal product name

Rilzabrutinib

Investigational medicinal product code

SAR444671

Other name

PRN1008

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received rilzabrutinib tablets 400 mg BID for 12 weeks.

Induction Treatment Period: Cohort B (Rilzabrutinib)

Arm description

Participants received rilzabrutinib tablets 400 mg orally BID for 12 weeks, along with glucocorticoid minimum starting dose of 20 mg/day and the maximum dose of 40 mg/day prednisone equivalent orally for a maximum of 4 weeks.

Arm type

Experimental

Investigational medicinal product name

Glucocorticoids

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received minimum starting dose of 20 mg/day and the maximum dose of 40 mg/day prednisone equivalent a maximum of 4 weeks.

Investigational medicinal product name

Rilzabrutinib

Investigational medicinal product code

SAR444671

Other name

PRN1008

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received rilzabrutinib tablets 400 mg BID for 12 weeks.

Number of subjects in period 1	Induction Treatment Period: Cohort A (Control)	Induction Treatment Period: Cohort A (Rilzabrutinib)	Induction Treatment Period: Cohort B (Rilzabrutinib)
Started	3	10	14
Completed	3	9	10
Not completed	0	1	4
Adverse event, serious fatal	-	-	1
Adverse event, non-fatal	-	1	1
Unspecified	-	-	1
Protocol deviation	-	-	1

Period 2 title

Crossover Treatment Period (12 Weeks)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Crossover Treatment Period: Rilzabrutinib

Arm description

Participants in Cohort A who were randomized to the control (glucocorticoid) arm and were unable to be weaned off glucocorticoid by end of induction treatment period entered a 12-week open-label rilzabrutinib cross-over period, to receive rilzabrutinib tablets 400 mg orally BID for 12 weeks, along with glucocorticoid minimum starting dose of 20 mg/day and the maximum dose of 40 mg/day prednisone equivalent orally for a maximum of 4 weeks.

Arm type

Experimental

Investigational medicinal product name

Rilzabrutinib

Investigational medicinal product code

SAR444671

Other name

PRN1008

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received rilzabrutinib tablets 400 mg BID for 12 weeks.

Investigational medicinal product name

Glucocorticoids

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received minimum starting dose of 20 mg/day and the maximum dose of 40 mg/day prednisone equivalent a maximum of 4 weeks.

Number of subjects in period 2 ^[1]	Crossover Treatment Period: Rilzabrutinib
Started	3
Completed	3

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: In Crossover treatment period, only participants from Control arm entered.

Period 3 title

Maintenance Treatment Period (40 Weeks)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Maintenance Treatment Period: Cohort A (Rilzabrutinib)

Arm description

Participants from Cohort A (rilzabrutinib) arm or those who completed the 12-week course of rilzabrutinib in crossover period, continued to receive rilzabrutinib tablets 400 mg orally BID for an additional 40 weeks.

Arm type

Experimental

Investigational medicinal product name

Rilzabrutinib

Investigational medicinal product code

SAR444671

Other name

PRN1008

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants were administered rilzabrutinib tablets 400 mg BID for 40 weeks.

Maintenance Treatment Period: Cohort B (Rilzabrutinib)

Arm description

Participants from Cohort B (rilzabrutinib) arm who completed the 12-week course of rilzabrutinib, continued to receive rilzabrutinib tablets 400 mg orally BID for an additional 40 weeks.

Arm type

Experimental

Investigational medicinal product name

Rilzabrutinib

Investigational medicinal product code

SAR444671

Other name

PRN1008

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants were administered rilzabrutinib tablets 400 mg BID for 40 weeks.

Number of subjects in period 3	Maintenance Treatment Period: Cohort A (Rilzabrutinib)	Maintenance Treatment Period: Cohort B (Rilzabrutinib)
Started	10	10
Completed	8	6
Not completed	2	4
Unspecified	2	4

Baseline characteristics

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Reporting group title

Induction Treatment Period: Cohort A (Control)

Reporting group description

Participants received glucocorticoid minimum starting dose of 20 milligram (mg)/day and the maximum dose of 40 mg/day prednisone equivalent orally for 12 weeks.

Reporting group title

Induction Treatment Period: Cohort A (Rilzabrutinib)

Reporting group description

Reporting group title

Induction Treatment Period: Cohort B (Rilzabrutinib)

Reporting group description

Reporting group values	Induction Treatment Period: Cohort A (Control)	Induction Treatment Period: Cohort A (Rilzabrutinib)	Induction Treatment Period: Cohort B (Rilzabrutinib)	Total
Number of subjects	3	10	14	27
Age categorical
Units: Subjects
Age Continuous
Units: years
arithmetic mean (standard deviation)	60.3 ( 22.74 )	63.4 ( 12.92 )	55.2 ( 14.10 )	-
Sex: Female, Male
Units: Participants
Female	1	3	2	6
Male	2	7	12	21
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0
Asian	1	1	7	9
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	1	0	0	1
White	1	7	5	13
More than one race	0	0	0	0
Other: Unknown or Not Reported	0	2	2	4

End points

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Reporting group title

Induction Treatment Period: Cohort A (Control)

Reporting group description

Participants received glucocorticoid minimum starting dose of 20 milligram (mg)/day and the maximum dose of 40 mg/day prednisone equivalent orally for 12 weeks.

Reporting group title

Induction Treatment Period: Cohort A (Rilzabrutinib)

Reporting group description

Reporting group title

Induction Treatment Period: Cohort B (Rilzabrutinib)

Reporting group description

Reporting group title

Crossover Treatment Period: Rilzabrutinib

Reporting group description

Reporting group title

Maintenance Treatment Period: Cohort A (Rilzabrutinib)

Reporting group description

Reporting group title

Maintenance Treatment Period: Cohort B (Rilzabrutinib)

Reporting group description

Participants from Cohort B (rilzabrutinib) arm who completed the 12-week course of rilzabrutinib, continued to receive rilzabrutinib tablets 400 mg orally BID for an additional 40 weeks.

Subject analysis set title

Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib)

Subject analysis set type

Per protocol

Subject analysis set description

Main TP included participants from Cohort A (12-week induction period and crossover TP), who received rilzabrutinib tablets 400 mg orally BID for 12 weeks, along with glucocorticoid minimum starting dose of 20 mg/day and the maximum dose of 40 mg/day prednisone equivalent orally for a maximum of 4 weeks. Participants from Cohort A (rilzabrutinib) arm or those who completed the 12-week course of rilzabrutinib in crossover period, continued to receive rilzabrutinib tablets 400 mg orally BID for an additional 40 weeks in Maintenance TP.

Subject analysis set title

Main+Maintenance Treatment Period:Cohort B (Rilzabrutinib)

Subject analysis set type

Per protocol

Subject analysis set description

Main TP included participants from Cohort B 12-week induction period, who received rilzabrutinib tablets 400 mg orally BID for 12 weeks, along with glucocorticoid minimum starting dose of 20 mg/day and the maximum dose of 40 mg/day prednisone equivalent orally for a maximum of 4 weeks. Participants from Cohort B (rilzabrutinib) arm who completed the 12-week course of rilzabrutinib, continued to receive rilzabrutinib tablets 400 mg orally BID for an additional 40 weeks in Maintenance TP.

Subject analysis set title

Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Main+Maintenance Treatment Period:Cohort B (Rilzabrutinib)

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib)

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib)

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Main+Maintenance Treatment Period:Cohort B (Rilzabrutinib)

Subject analysis set type

Per protocol

Subject analysis set description

Primary: Induction Treatment Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), TEAEs Leading to Discontinuation and Possible Glucocorticoid-Related TEAEs

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End point title

Induction Treatment Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), TEAEs Leading to Discontinuation and Possible Glucocorticoid-Related TEAEs ^[1]

End point description

An AE was any untoward medical occurrence in a participant, temporally associated with use of study treatment, whether or not considered related. TEAEs were defined as AEs that developed, worsened or became serious during TE period (defined as time from first administration of study treatment [Day 1] to last administration of study treatment+7 days). SAE: Any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs leading to discontinuation of study treatment and possible glucocorticoid-related TEAEs are also reported. Safety population (Cohort A) and Rilzabrutinib-treated population (Cohort B) consisted of all participants who received at least 1 dose of study treatment.

End point type

Primary

End point timeframe

From first dose of study treatment (Day 1) up to last dose of study treatment + 7 days (up to approximately 13 weeks)

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 additional statistical analysis was prespecified for this endpoint.

End point values	Induction Treatment Period: Cohort A (Control)	Induction Treatment Period: Cohort A (Rilzabrutinib)	Induction Treatment Period: Cohort B (Rilzabrutinib)
Number of subjects analysed	3	10	14
Units: participants
TEAEs	3	8	13
TESAEs	0	1	1
TEAEs leading to discontinuation	0	1	2
Possible glucocorticoid-related TEAEs	2	1	9

No statistical analyses for this end point

Primary: Main + Maintenance Treatment Period: Number of Participants With Treatment-Emergent Adverse Events, Treatment-Emergent Serious Adverse Events, TEAEs Leading to Discontinuation and Possible Glucocorticoid-Related TEAEs

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End point title

Main + Maintenance Treatment Period: Number of Participants With Treatment-Emergent Adverse Events, Treatment-Emergent Serious Adverse Events, TEAEs Leading to Discontinuation and Possible Glucocorticoid-Related TEAEs ^[2]

End point description

TEAEs were defined as the AEs that developed, worsened or became serious during the treatment-emergent period (defined as time from first administration of study treatment [Day 1] to last administration of study treatment + 7 days). SAE: Any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs leading to discontinuation of study treatment and possible glucocorticoid-related TEAEs are also reported. Rilzabrutinib-treated population (Cohort B): all participants who received at least 1 dose of study treatment; (Cohort A): a subset of safety population consisted of only those participants randomized to the rilzabrutinib and to Control arm who crossed over and who received at least 1 dose of rilzabrutinib.

End point type

Primary

End point timeframe

From first dose of study treatment (Day 1) up to last dose of study treatment + 7 days (up to approximately 53 weeks)

Notes
[2] - 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 additional statistical analysis was prespecified for this endpoint.

End point values	Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib)	Main+Maintenance Treatment Period:Cohort B (Rilzabrutinib)
Number of subjects analysed	13	14
Units: participants
TEAEs	10	13
TESAEs	1	1
TEAEs leading to discontinuation	2	3
Possible glucocorticoid-related TEAEs	2	9

No statistical analyses for this end point

Primary: Induction Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities (PCSAs) for Vital Signs

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End point title

Induction Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities (PCSAs) for Vital Signs ^[3]

End point description

Vital signs assessments included systolic blood pressure (SBP), diastolic blood pressure (DSP), pulse rate (PR), and weight. Criteria for PCSA: pulse rate: <=50 beats per minute (bpm) and decrease from baseline >=20 bpm, >=120 bpm and increase from baseline >=20 bpm; SBP: <=95 millimeters of mercury (mmHg) and decrease from baseline >=20 mmHg, >=160 mmHg and increase from baseline >=20 mmHg, <=-20 mmHg; DBP: <=45 mmHg and decrease from baseline >=10 mmHg, >=110 mmHg and increase from baseline >=10 mmHg, <=-10 mmHg; Weight: >=5 percentage (%) increase from baseline, >=5% decrease from baseline. Safety population (Cohort A) and Rilzabrutinib-treated population (Cohort B) consisted of all participants who received at least 1 dose of study treatment.

End point type

Primary

End point timeframe

From first dose of study treatment (Day 1) up to last dose of study treatment + 7 days (up to approximately 13 weeks)

Notes
[3] - 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 additional statistical analysis was prespecified for this endpoint.

End point values	Induction Treatment Period: Cohort A (Control)	Induction Treatment Period: Cohort A (Rilzabrutinib)	Induction Treatment Period: Cohort B (Rilzabrutinib)
Number of subjects analysed	3	10	14
Units: participants
PR: <=50 bpm and decrease from baseline >=20 bpm	0	0	0
PR: >=120 bpm and increase from baseline >=20 bpm	0	0	0
SBP:<=95 mmHg and decrease from baseline >=20 mmHg	0	0	0
SBP:>=160mmHg and increase from baseline >=20 mmHg	0	0	0
SBP: <=-20 mmHg	0	0	0
DBP:<=45 mmHg and decrease from baseline >=10 mmHg	0	0	0
DBP:>=110mmHg and increase from baseline >=10 mmHg	0	0	0
DBP: <=-10 mmHg	0	0	0
Weight: >=5% increase from baseline	2	0	1
Weight: >=5% decrease from baseline	0	2	1

No statistical analyses for this end point

Primary: Main + Maintenance Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Vital Signs

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End point title

Main + Maintenance Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Vital Signs ^[4]

End point description

Vital signs assessments included SBP, DSP, pulse rate, and weight. Criteria for PCSA: PR: <=50 bpm and decrease from baseline >=20 bpm, >=120 bpm and increase from baseline >=20 bpm; SBP: <=95 mmHg and decrease from baseline >=20 mmHg, >=160 mmHg and increase from baseline >=20 mmHg, <=-20 mmHg; DBP: <=45 mmHg and decrease from baseline >=10 mmHg, >=110 mmHg and increase from baseline >=10 mmHg, <=-10 mmHg; Weight: >=5% increase from baseline, >=5% decrease from baseline. Rilzabrutinib-treated population (Cohort B): all participants who received at least 1 dose of study treatment; (Cohort A): a subset of safety population consisted of only those participants randomized to the rilzabrutinib and to Control arm who crossed over and who received at least 1 dose of rilzabrutinib.

End point type

Primary

End point timeframe

From first dose of study treatment (Day 1) up to last dose of study treatment + 7 days (up to approximately 53 weeks)

Notes
[4] - 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 additional statistical analysis was prespecified for this endpoint.

End point values	Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib)	Main+Maintenance Treatment Period:Cohort B (Rilzabrutinib)
Number of subjects analysed	13	14
Units: participants
PR: <=50 bpm and decrease from baseline >=20 bpm	0	0
PR: >=120 bpm and increase from baseline >=20 bpm	0	0
SBP:<=95 mmHg and decrease from baseline >=20 mmHg	0	0
SBP:>=160mmHg and increase from baseline >=20 mmHg	0	0
SBP: <=-20 mmHg	0	0
DBP:<=45 mmHg and decrease from baseline >=10 mmHg	0	0
DBP:>=110mmHg and increase from baseline >=10 mmHg	0	0
DBP: <=-10 mmHg	0	0
Weight: >=5% increase from baseline	2	1
Weight: >=5% decrease from baseline	5	3

No statistical analyses for this end point

Primary: Induction Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Hematology and Coagulation Parameters

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End point title

Induction Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Hematology and Coagulation Parameters ^[5]

End point description

Criteria for PCSA: Leukocytes <3.0 x 10^9 per liter (/L) (Non-Black [NB]) or < 2 x 10^9/L (Black[B]), >=16.0 x 10^9/L; Lymphocytes >4.0 x 10^9/L; Neutrophils <1.5 x 10^9/L (NB) or <1.0 x 10^9/L (B); Monocytes >0.7 x 10^9/L; Basophils >0.1 x 10^9/L; Eosinophils: >0.5 x 10^9/L, >1 upper limit of normal range(ULN) (if ULN >=0.5 Giga/L); Hemoglobin (Hb): <=115 grams per liter (g/L) (M); <=95 g/L (F), >=185 g/L (M); >=165 g/L (F), decrease from baseline >=20 g/L; Hematocrit: <=0.37 volume per volume (v/v) (M); <=0.32 v/v (F), >=0.55 v/v (M); >=0.5 v/v (F); Erythrocytes >=6.0 x 10^12/L; Platelets: <100 x 10^9/L, >=700 x 10^9/L. Safety population (Cohort A) and Rilzabrutinib-treated population (Cohort B) consisted of all participants who received at least 1 dose of study treatment.

End point type

Primary

End point timeframe

From first dose of study treatment (Day 1) up to last dose of study treatment + 7 days (up to approximately 13 weeks)

Notes
[5] - 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 additional statistical analysis was prespecified for this endpoint.

End point values	Induction Treatment Period: Cohort A (Control)	Induction Treatment Period: Cohort A (Rilzabrutinib)	Induction Treatment Period: Cohort B (Rilzabrutinib)
Number of subjects analysed	3	10	14
Units: participants
Leukocytes:<3.0 x 10^9/L (NB) or <2.0 x 10^9/L (B)	0	0	0
Leukocytes: >=16.0 x 10^9/L	0	2	2
Lymphocytes: >4.0 x 10^9/L	1	1	3
Neutrophils:<1.5 x 10^9/L (NB) or <1.0 x10^9/L (B)	1	0	1
Monocytes: >0.7 x 10^9/L	2	6	8
Basophils: >0.1 x 10^9/L	3	2	5
Eosinophils: >0.5 x 10^9/L	2	5	5
Eosinophils: >1 ULN (if ULN >=0.5 Giga/L)	0	0	0
Hb: <=115 g/L (M); <=95 g/L (F)	0	0	1
Hb: >=185 g/L (M); >=165 g/L (F)	0	0	0
Hb: Decrease from baseline >=20 g/L	0	0	3
Hematocrit: <=0.37 v/v (M); <=0.32 v/v (F)	0	1	2
Hematocrit: >=0.55 v/v (M); >=0.5 v/v (F)	1	0	0
Erythrocytes: >=6.0 x 10^12/L	0	0	1
Platelets: <100 x 10^9/L	0	0	0
Platelets: >=700 x 10^9/L	0	0	0
Coagulation parameter	0	0	0

No statistical analyses for this end point

Primary: Main + Maintenance Treatment Period:Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Hematology and Coagulation Parameters

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End point title

Main + Maintenance Treatment Period:Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Hematology and Coagulation Parameters ^[6]

End point description

Criteria for PCSA: Leukocytes <3.0 x 10^9/L (NB) or < 2 x 10^9/L (B), >=16.0 x 10^9/L; Lymphocytes >4.0 x 10^9/L; Neutrophils <1.5 x 10^9/L (NB) or <1.0 x 10^9/L (B); Monocytes >0.7 x 10^9/L; Basophils >0.1 x 10^9/L; Eosinophils: >0.5 x 10^9/L, >1 ULN (if ULN >=0.5 Giga/L); Hb: <=115 g/L (M); <=95 g/L (F), >=185 g/L (M); >=165 g/L (F), decrease from baseline >=20 g/L; Hematocrit: <=0.37 v/v (M); <=0.32 v/v (F), >=0.55 v/v (M); >=0.5 v/v (F); Erythrocytes >=6.0 x 10^12/L; Platelets: <100 x 10^9/L, >=700 x 10^9/L. Rilzabrutinib-treated population (Cohort B): all participants who received at least 1 dose of study treatment; (Cohort A): a subset of safety population consisted of only those participants randomized to the rilzabrutinib and to Control arm who crossed over and who received at least 1 dose of rilzabrutinib.

End point type

Primary

End point timeframe

From first dose of study treatment (Day 1) up to last dose of study treatment + 7 days (up to approximately 53 weeks)

Notes
[6] - 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 additional statistical analysis was prespecified for this endpoint.

End point values	Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib)	Main+Maintenance Treatment Period:Cohort B (Rilzabrutinib)
Number of subjects analysed	13	14
Units: participants
Leukocytes:<3.0 x 10^9/L (NB) or <2.0 x 10^9/L (B)	0	0
Leukocytes: >=16.0 x 10^9/L	2	2
Lymphocytes: >4.0 x 10^9/L	3	3
Neutrophils:<1.5 x 10^9/L (NB) or <1.0 x10^9/L (B)	0	1
Monocytes: >0.7 x 10^9/L	7	10
Basophils: >0.1 x 10^9/L	3	5
Eosinophils: >0.5 x 10^9/L	8	5
Eosinophils: >1 ULN (if ULN >=0.5 Giga/L)	0	0
Hb: <=115 g/L (M); <=95 g/L (F)	0	1
Hb: >=185 g/L (M); >=165 g/L (F)	0	0
Hb: Decrease from baseline >=20 g/L	1	3
Hematocrit: <=0.37 v/v (M); <=0.32 v/v (F)	1	2
Hematocrit: >=0.55 v/v (M); >=0.5 v/v (F)	0	0
Erythrocytes: >=6.0 x 10^12/L	1	1
Platelets: <100 x 10^9/L	1	0
Platelets: >=700 x 10^9/L	0	0
Coagulation parameters	0	0

No statistical analyses for this end point

Primary: Induction Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Chemistry Parameters

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End point title

Induction Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Chemistry Parameters ^[7]

End point description

Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST): >3, >5, >10, and >20 ULN; Alkaline phosphatase (ALP) >1.5 ULN; Bilirubin: >1.5 and >2 ULN; Creatine kinase: >3 and >10 ULN; Creatinine clearance (CrC): <15 (end stage renal disease), >=15-<30 (severe decrease in glomerular filtration rate [GFR]), >=30-<60 (moderate decrease in GFR), >=60-<90 (mild decrease in GFR), >=90 (normal GFR); Creatinine: >=150 micromoles per liter (mcmol/L) (Adults), >=30% change from baseline, >=100% change from baseline; Urea nitrogen >=17 millimoles per liter (mmol/L); Chloride: <80 and >115 mmol/L; Sodium: <=129 and >=160 mmol/L; Potassium: <3 and >=5.5 mmol/L; Lipase >=3 ULN; Amylase >=3 ULN; Glucose: <=3.9 mmol/L and <lower limit of normal range (LLN), >=7 mmol/L; Albumin <=25 g/L. Safety population (Cohort A) and Rilzabrutinib-treated population (Cohort B) consisted of all participants who received at least 1 dose of study treatment.

End point type

Primary

End point timeframe

From first dose of study treatment (Day 1) up to last dose of study treatment + 7 days (up to approximately 13 weeks)

Notes
[7] - 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 additional statistical analysis was prespecified for this endpoint.

End point values	Induction Treatment Period: Cohort A (Control)	Induction Treatment Period: Cohort A (Rilzabrutinib)	Induction Treatment Period: Cohort B (Rilzabrutinib)
Number of subjects analysed	3	10	14
Units: participants
ALT: >3 ULN	0	0	1
ALT: >5 ULN	0	0	1
ALT: >10 ULN	0	0	0
ALT: >20 ULN	0	0	0
AST: >3 ULN	0	0	1
AST: >5 ULN	0	0	1
AST: >10 ULN	0	0	0
AST: >20 ULN	0	0	0
ALP: >1.5 ULN	0	1	2
Bilirubin: >1.5 ULN	0	0	1
Bilirubin: >2 ULN	0	0	1
Creatine kinase: >3 ULN	0	0	0
Creatine kinase: >10 ULN	0	0	0
CrC: <15 (end stage renal disease)	0	0	0
CrC: >=15-<30 (severe decrease in GFR)	0	0	0
CrC: >=30-<60 (moderate decrease in GFR)	0	0	1
CrC: >=60-<90 (mild decrease in GFR)	0	0	0
CrC: >=90 (normal GFR)	0	0	0
Creatinine: >=150 mcmol/L (Adults)	0	1	1
Creatinine: >=30% change from baseline	1	3	8
Creatinine: >=100% change from baseline	0	0	0
Urea nitrogen: >=17 mmol/L	0	0	0
Chloride: <80 mmol/L	1	0	0
Chloride: >115 mmol/L	0	0	0
Sodium: <=129 mmol/L	1	1	1
Sodium: >=160 mmol/L	0	0	0
Potassium: <3 mmol/L	1	0	0
Potassium: >=5.5 mmol/L	0	0	2
Lipase: >=3 ULN	0	1	1
Amylase: >=3 ULN	0	0	0
Glucose: <=3.9 mmol/L and <LLN	0	1	1
Glucose: >=7 mmol/L	1	6	6
Albumin: <=25 g/L	0	0	0

No statistical analyses for this end point

Primary: Main + Maintenance Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Chemistry Parameters

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End point title

Main + Maintenance Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Chemistry Parameters ^[8]

End point description

Criteria for PCSA: ALT and AST: >3 ULN, >5 ULN, >10 ULN, >20 ULN; ALP >1.5 ULN; Bilirubin: >1.5 ULN, >2 ULN; Creatine kinase: >3 ULN, >10 ULN; CrC: <15 (end stage renal disease), >=15-<30 (severe decrease in GFR), >=30-<60 (moderate decrease in GFR), >=60-<90 (mild decrease in GFR), >=90 (normal GFR); Creatinine: >=150 mcmol/L (Adults), >=30% change from baseline, >=100% change from baseline; Urea nitrogen >=17 mmol/L; Chloride: <80 mmol/L, >115 mmol/L; Sodium: <=129 mmol/L, >=160 mmol/L; Potassium: <3 mmol/L, >=5.5 mmol/L; Lipase >=3 ULN; Amylase >=3 ULN; Glucose: <=3.9 mmol/L and < LLN, >=7 mmol/L; Albumin <=25 g/L. Rilzabrutinib-treated population (Cohort B): all participants who received at least 1 dose of study treatment; (Cohort A): a subset of safety population consisted of only those participants randomized to the rilzabrutinib and to Control arm who crossed over and who received at least 1 dose of rilzabrutinib.

End point type

Primary

End point timeframe

From first dose of study treatment (Day 1) up to last dose of study treatment + 7 days (up to approximately 53 weeks)

Notes
[8] - 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 additional statistical analysis was prespecified for this endpoint.

End point values	Main+Maintenance Treatment Period:Cohort B (Rilzabrutinib)	Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib
Number of subjects analysed	14	13
Units: participants
ALT: >3 ULN	2	0
ALT: >5 ULN	2	0
ALT: >10 ULN	1	0
ALT: >20 ULN	0	0
AST: >3 ULN	2	0
AST: >5 ULN	2	0
AST: >10 ULN	1	0
AST: >20 ULN	1	0
ALP: >1.5 ULN	2	1
Bilirubin: >1.5 ULN	2	0
Bilirubin: >2 ULN	1	0
Creatine kinase: >3 ULN	1	0
Creatine kinase: >10 ULN	0	0
CrC: <15 (end stage renal disease)	0	0
CrC: >=15-<30 (severe decrease in GFR)	0	0
CrC: >=30-<60 (moderate decrease in GFR)	1	2
CrC: >=60-<90 (mild decrease in GFR)	0	1
CrC: >=90 (normal GFR)	1	1
Creatinine: >=150 mcmol/L (Adults)	1	1
Creatinine: >=30% change from baseline	13	5
Creatinine: >=100% change from baseline	0	0
Urea nitrogen: >=17 mmol/L	0	0
Chloride: <80 mmol/L	1	1
Chloride: >115 mmol/L	0	0
Sodium: <=129 mmol/L	1	2
Sodium: >=160 mmol/L	0	0
Potassium: <3 mmol/L	0	1
Potassium: >=5.5 mmol/L	2	2
Lipase: >=3 ULN	2	1
Amylase: >=3 ULN	0	0
Glucose: <=3.9 mmol/L and <LLN	2	2
Glucose: >=7 mmol/L	7	7
Albumin: <=25 g/L	0	0

No statistical analyses for this end point

Primary: Induction Treatment Period:Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Urinalysis

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End point title

Induction Treatment Period:Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Urinalysis ^[9]

End point description

PCSA criteria for urinalysis included: pH <=4.6 and pH >=8. Safety population (Cohort A) and Rilzabrutinib-treated population (Cohort B) consisted of all participants who received at least 1 dose of study treatment.

End point type

Primary

End point timeframe

From first dose of study treatment (Day 1) up to last dose of study treatment + 7 days (up to approximately 13 weeks)

Notes
[9] - 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 additional statistical analysis was prespecified for this endpoint.

End point values	Induction Treatment Period: Cohort A (Control)	Induction Treatment Period: Cohort A (Rilzabrutinib)	Induction Treatment Period: Cohort B (Rilzabrutinib)
Number of subjects analysed	3	10	14
Units: participants
pH: <=4.6	0	0	0
pH: >=8	0	0	1

No statistical analyses for this end point

Primary: Main + Maintenance Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Urinalysis

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End point title

Main + Maintenance Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Urinalysis ^[10]

End point description

PCSA criteria for urinalysis included: pH <=4.6 and pH >=8. Rilzabrutinib-treated population (Cohort B): all participants who received at least 1 dose of study treatment; (Cohort A): a subset of safety population consisted of only those participants randomized to the rilzabrutinib and to Control arm who crossed over and who received at least 1 dose of rilzabrutinib.

End point type

Primary

End point timeframe

From first dose of study treatment (Day 1) up to last dose of study treatment + 7 days (up to approximately 53 weeks)

Notes
[10] - 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 additional statistical analysis was prespecified for this endpoint.

End point values	Main+Maintenance Treatment Period:Cohort B (Rilzabrutinib)	Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib
Number of subjects analysed	14	13
Units: participants
pH: <=4.6	0	0
pH: >=8	1	1

No statistical analyses for this end point

Primary: Percentage of Participants Without Disease Flare Following the First Dose of Rilzabrutinib

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End point title

Percentage of Participants Without Disease Flare Following the First Dose of Rilzabrutinib ^[11]

End point description

Disease flare was defined as any of the following criteria: An increase in immunoglobulin G subclass 4-related disease (IgG4-RD) responder index (RI) >2 from the prior assessment; Initiation of rescue treatment following the first dose of rilzabrutinib until the end of treatment; Any end of study reason related to the disease under treatment. Rilzabrutinib-treated population (Cohort B): all participants who received at least 1 dose of study treatment; (Cohort A): a subset of safety population consisted of only those participants randomized to the rilzabrutinib and to control arm who crossed over and who received at least 1 dose of rilzabrutinib. It was pre-specified in Statistical Analysis Plan (SAP), efficacy analysis was planned only for Main+Maintenance period.

End point type

Primary

End point timeframe

Up to end of treatment (52 Weeks)

Notes
[11] - 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 additional statistical analysis was prespecified for this endpoint.

End point values	Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib)	Main+Maintenance Treatment Period:Cohort B (Rilzabrutinib)
Number of subjects analysed	13	14
Units: percentage of participants
number (not applicable)	76.9	64.3

No statistical analyses for this end point

Secondary: Percentage of Participants With Reduction From Baseline Immunoglobulin G Subclass 4-Related Disease Responder Index Activity Score by >=2 Points Over Time

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End point title

Percentage of Participants With Reduction From Baseline Immunoglobulin G Subclass 4-Related Disease Responder Index Activity Score by >=2 Points Over Time

End point description

The IgG4-RD RI was designed to detect changes in disease activity in each affected organ system in a composite scoring system, assessed using computed tomography scan (CT scan). Physician assessed status by assigning a 0-3 score after organ/site as follows: 0=absence of active disease in that site. 1=improved but persistent activity in that site. 2=new or recurrent disease activity in that site while off treatment, or unchanged from previous visit. 3=worse or new despite treatment. Baseline= last observation recorded prior to first dose of study treatment. Rilzabrutinib-treated population (Cohort B): all participants who received at least 1 dose of study treatment; (Cohort A):a subset of safety population. Here, ‘n’ = number of participants analyzed at specific time point. It was pre-specified in SAP, efficacy analysis was planned for Main+Maintenance period.

End point type

Secondary

End point timeframe

Baseline (Week 0) and Weeks 12, 24, 36, 48, 52, and end of study (Week 56)

End point values	Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib)	Main+Maintenance Treatment Period:Cohort B (Rilzabrutinib)
Number of subjects analysed	13	12
Units: percentage of participants
number (not applicable)
Week 12 (n = 13,11)	69.2	100.0
Week 24 (n = 10,5)	80.0	100.0
Week 36 (n = 9,6)	66.7	100.0
Week 48 (n = 7,6)	85.7	100.0
Week 52 (n = 8,6)	87.5	100.0
End of study (Week 56) (n = 8,12)	75.0	100.0

No statistical analyses for this end point

Secondary: Percentage of Participants With Reduction From Baseline Immunoglobulin G4-Related Disease Responder Index Activity Score=0 Over Time

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End point title

Percentage of Participants With Reduction From Baseline Immunoglobulin G4-Related Disease Responder Index Activity Score=0 Over Time

End point description

The IgG4-RD RI was designed to detect changes in disease activity in each affected organ system in a composite scoring system, assessed using CT scan. The physician assessed status by assigning a 0-3 score after the organ/site as follows: 0=absence of active disease in that site. 1=improved but persistent activity in that site. 2=new or recurrent disease activity in that site while off treatment, or unchanged from previous visit. 3=worse or new despite treatment. Baseline= last observation recorded prior to the first dose of study treatment. Rilzabrutinib-treated population (Cohort B): all participants who received at least 1 dose of study treatment; (Cohort A): a subset of safety population. Here, ‘n’ = number of participants analyzed at specific time point. It was pre-specified in SAP, efficacy analysis was planned only for Main+Maintenance period.

End point type

Secondary

End point timeframe

Baseline (Week 0) and Weeks 12, 24, 36, 48, 52, and End of study (Week 56)

End point values	Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib	Main+Maintenance Treatment Period:Cohort B (Rilzabrutinib)
Number of subjects analysed	13	12
Units: percentage of participants
number (not applicable)
Week 12 (n = 13,11)	7.7	0.0
Week 24 (n = 10,5)	10.0	0.0
Week 36 (n = 9,6)	11.1	0.0
Week 48 (n = 7,6)	14.3	0.0
Week 52 (n = 8,6)	12.5	16.7
End of study (Week 56) (n = 8,12)	0.0	0.0

No statistical analyses for this end point

Secondary: Change From Baseline in Immunoglobulin G4-Related Disease Responder Index Over Time

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End point title

Change From Baseline in Immunoglobulin G4-Related Disease Responder Index Over Time

End point description

The IgG4-RD RI was designed to detect changes in disease activity in each affected organ system in a composite scoring system, assessed using CT scans. At specified visits, the physician assessed the status by assigning a 0-3 score after the organ/site as follows: 0=absence of active disease in that site. 1=improved but persistent activity in that site. 2=new or recurrent disease activity in that site while off treatment, or unchanged from previous visit. 3=worse or new despite treatment. Baseline was defined as the last observation recorded prior to the first dose of study treatment. Rilzabrutinib-treated population (Cohort B): all participants who received at least 1 dose of study treatment; (Cohort A): a subset of safety population. Here, ‘n’ = number of participants analyzed at specific time point. It was pre-specified in SAP, efficacy analysis was planned only for Main+Maintenance period.

End point type

Secondary

End point timeframe

Baseline (Week 0) and Weeks 12, 24, 36, 48, 52, and end of study (Week 56)

End point values	Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib)	Main+Maintenance Treatment Period:Cohort B (Rilzabrutinib)
Number of subjects analysed	13	12
Units: score on a scale
arithmetic mean (standard deviation)
Week 12 (n = 13, 11)	-5.31 ( 4.131 )	-11.91 ( 5.467 )
Week 24 (n = 10, 5)	-6.90 ( 3.784 )	-10.60 ( 1.817 )
Week 36 (n = 9,6)	-5.22 ( 5.357 )	-14.33 ( 6.055 )
Week 48 (n = 7,6)	-7.29 ( 4.231 )	-14.17 ( 5.707 )
Week 52 (n = 8,6)	-7.50 ( 3.928 )	-15.00 ( 6.481 )
End of study (Week 56) (n = 8,12)	-5.50 ( 4.440 )	-11.17 ( 5.132 )

No statistical analyses for this end point

Secondary: Change From Baseline in Immunoglobulin G4-Related Disease Damage Over Time

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End point title

Change From Baseline in Immunoglobulin G4-Related Disease Damage Over Time

End point description

Damage was defined as the occurrence of permanent tissue injury or organ dysfunction that results from active or previously active IgG4-RD. Damage in this context does NOT refer to treatment-induced injury. Baseline was defined as the last observation recorded prior to the first dose of study treatment. The IgG4-RD RI was designed to detect changes in disease activity in each affected organ system in a composite scoring system, assessed using CT scans. At specified visits, the physician assessed the status by assigning a 0-3 score after the organ/site as follows: 0=absence of active disease in that site. 1=improved but persistent activity in that site. 2=new or recurrent disease activity in that site while off treatment, or unchanged from previous visit. 3=worse or new despite treatment. Rilzabrutinib-treated population. Here, ‘n’ = number of participants analyzed at specific time point. It was pre-specified in SAP, efficacy analysis was planned only for Main+Maintenance period.

End point type

Secondary

End point timeframe

Baseline (Week 0) and Weeks 12, 24, 36, 48, 52, and end of study (Week 56)

End point values	Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib)	Main+Maintenance Treatment Period:Cohort B (Rilzabrutinib)
Number of subjects analysed	13	12
Units: score on a scale
arithmetic mean (standard deviation)
Week 12 (n = 13,11)	0.15 ( 0.899 )	0.36 ( 0.505 )
Week 24 (n = 10,5)	0.00 ( 0.943 )	0.20 ( 0.447 )
Week 36 (n = 9,6)	-0.22 ( 0.667 )	0.33 ( 0.516 )
Week 48 (n = 7,6)	-0.71 ( 1.254 )	0.33 ( 0.516 )
Week 52 (n = 8,6)	0.13 ( 1.126 )	0.17 ( 0.408 )
End of study (Week 56) (n = 8,12)	0.00 ( 0.756 )	0.25 ( 0.452 )

No statistical analyses for this end point

Secondary: Change From Baseline of Each Subclass of the Following Serological Markers: IgG4, IgG1, IgG, IgM, Complement C3 and C4 at Week 52

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End point title

Change From Baseline of Each Subclass of the Following Serological Markers: IgG4, IgG1, IgG, IgM, Complement C3 and C4 at Week 52

End point description

Serum samples were collected at specified timepoints to assess the changes in serum concentrations of immunoglobulin G subclass 4 (IgG4), immunoglobulin G subclass 1 (IgG1),immunoglobulin G (IgG), immunoglobulin M (IgM), complement C3, and complement C4 serological parameters. Baseline was defined as the last observation recorded prior to the first dose of study treatment. Rilzabrutinib-treated population (Cohort B): all participants who received at least 1 dose of study treatment; (Cohort A): a subset of safety population consisted of only those participants randomized to the rilzabrutinib and to Control arm who crossed over and who received at least 1 dose of rilzabrutinib. Here, ‘n’ = number of participants analyzed at specific time point. It was pre-specified in SAP, efficacy analysis was planned only for Main+Maintenance period.

End point type

Secondary

End point timeframe

Baseline (Week 0) and end of treatment (Week 52)

End point values	Main+Maintenance Treatment Period:Cohort B (Rilzabrutinib)	Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib)
Number of subjects analysed	8	8
Units: milligram per deciliter
arithmetic mean (standard deviation)
IgG4 (n = 7, 7)	-114.757 ( 93.1197 )	-223.671 ( 329.2337 )
IgG1 (n = 7, 7)	-130.414 ( 84.0370 )	-74.957 ( 106.7538 )
IgG (n = 7, 7)	-150.857 ( 181.8859 )	-405.286 ( 574.3781 )
IgM (n = 8, 8)	-12.750 ( 10.6335 )	1.000 ( 49.5955 )
Complement C3 (n = 8, 8)	-5.250 ( 14.5283 )	17.750 ( 23.7231 )
Complement C4 (n = 8, 8)	-0.875 ( 5.1669 )	6.875 ( 6.3794 )

No statistical analyses for this end point

Secondary: Change From Baseline of Each Subclass of the Following Serological Marker: IgE at Week 52

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End point title

Change From Baseline of Each Subclass of the Following Serological Marker: IgE at Week 52

End point description

Serum samples were collected at specified timepoints to assess the changes in serum concentrations of immunoglobulin E (IgE) serological parameter. Baseline was defined as the last observation recorded prior to the first dose of study treatment. Rilzabrutinib-treated population (Cohort B): all participants who received at least 1 dose of study treatment; (Cohort A): a subset of safety population consisted of only those participants randomized to the rilzabrutinib and to Control arm who crossed over and who received at least 1 dose of rilzabrutinib. Only participants with data collected at specified timepoints are reported. It was pre-specified in SAP, efficacy analysis was planned only for Main+Maintenance period.

End point type

Secondary

End point timeframe

Baseline (Week 0) and end of treatment (Week 52)

End point values	Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib)	Main+Maintenance Treatment Period:Cohort B (Rilzabrutinib)
Number of subjects analysed	7	8
Units: International units per millilter
arithmetic mean (standard deviation)	297.529 ( 661.2851 )	-49.025 ( 494.3543 )

No statistical analyses for this end point

Secondary: Percentage of Participants who Achieved a Reduction in Baseline Serum Immunoglobulin G Subclass 4 Level of 10% Over Time

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End point title

Percentage of Participants who Achieved a Reduction in Baseline Serum Immunoglobulin G Subclass 4 Level of 10% Over Time

End point description

Serum samples were collected at specified timepoints to assess percentage of participants who achieved a reduction in baseline serum IgG4 level of 10% over time. Baseline was defined as the last observation recorded prior to the first dose of study treatment. Rilzabrutinib-treated population (Cohort B): all participants who received at least 1 dose of study treatment; (Cohort A): a subset of safety population consisted of only those participants randomized to the rilzabrutinib and to control arm who crossed over and who received at least 1 dose of rilzabrutinib. Here, ‘n’ = number of participants analyzed at specific time point. It was pre-specified in SAP, efficacy analysis was planned only for Main+Maintenance period.

End point type

Secondary

End point timeframe

Baseline (Week 0) and Weeks 2, 4, 12, 24, 52, and end of study (Week 56)

End point values	Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib)	Main+Maintenance Treatment Period:Cohort B (Rilzabrutinib)
Number of subjects analysed	13	14
Units: percentage of participants
number (not applicable)
Week 2 (n = 9, 14)	77.8	35.7
Week 4 (n = 13, 13)	61.5	53.8
Week 12 (n = 12, 11)	50.0	63.6
Week 24 (n = 10,7)	60.0	85.7
Week 52 (n = 8,6)	75.0	83.3
End of study (Week 56) (n = 12,12)	33.3	75.0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

AEs collected from first dose of study treatment (Day 1) up to last dose +7 days (up to 13 [Induction TP] and 53 weeks [Main+Maintenance TP]). Death was assessed from signing of informed consent form (Week -4) to end of follow-up, approximately 216 weeks.

Adverse event reporting additional description

Analysis was performed on safety population. It was pre-specified in SAP, separate safety analysis for main treatment period was not planned.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

27.0

Reporting group title

Main Treatment Period: Rilzabrutinib (Cohort B)

Reporting group description

Reporting group title

Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib)

Reporting group description

Reporting group title

Induction Treatment Period: Cohort A (Rilzabrutinib)

Reporting group description

Reporting group title

Induction Treatment Period: Cohort A (Control)

Reporting group description

Participants received glucocorticoid minimum starting dose of 20 mg/day and the maximum dose of 40 mg/day prednisone equivalent orally for 12 weeks.

Serious adverse events	Main Treatment Period: Rilzabrutinib (Cohort B)	Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib)	Induction Treatment Period: Cohort A (Rilzabrutinib)	Induction Treatment Period: Cohort A (Control)
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 14 (7.14%)	1 / 13 (7.69%)	1 / 10 (10.00%)	0 / 3 (0.00%)
number of deaths (all causes)	1	0	0	0
number of deaths resulting from adverse events
Respiratory, thoracic and mediastinal disorders
Pneumonitis Aspiration
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute Kidney Injury
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Campylobacter Infection
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Main Treatment Period: Rilzabrutinib (Cohort B)	Main+Maintenance Treatment Period:Cohort A (All Rilzabrutinib)	Induction Treatment Period: Cohort A (Rilzabrutinib)	Induction Treatment Period: Cohort A (Control)
Total subjects affected by non serious adverse events
subjects affected / exposed	13 / 14 (92.86%)	10 / 13 (76.92%)	8 / 10 (80.00%)	3 / 3 (100.00%)
Vascular disorders
Thrombophlebitis
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Intermittent Claudication
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences all number	0	1	1	0
Hypertension
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences all number	0	1	1	0
Chest Pain
subjects affected / exposed	1 / 14 (7.14%)	1 / 13 (7.69%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Fatigue
subjects affected / exposed	2 / 14 (14.29%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	3	0	0	0
Immune system disorders
Seasonal Allergy
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Allergic Sinusitis
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Rhinorrhoea
subjects affected / exposed	1 / 14 (7.14%)	1 / 13 (7.69%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences all number	1	1	1	0
Oropharyngeal Pain
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Psychiatric disorders
Insomnia
subjects affected / exposed	1 / 14 (7.14%)	1 / 13 (7.69%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences all number	1	1	1	0
Confusional State
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Investigations
Blood Creatinine Increased
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences all number	0	1	1	0
Blood Glucose Increased
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Transaminases Increased
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences all number	0	1	1	0
Injury, poisoning and procedural complications
Arthropod Sting
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Alcohol Poisoning
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Arthropod Bite
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Meniscus Injury
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences all number	0	1	1	0
Muscle Strain
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0
Periorbital Haemorrhage
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Skin Laceration
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Cardiac disorders
Palpitations
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	2	0	0	0
Nervous system disorders
Dizziness
subjects affected / exposed	2 / 14 (14.29%)	3 / 13 (23.08%)	2 / 10 (20.00%)	0 / 3 (0.00%)
occurrences all number	2	3	2	0
Cognitive Disorder
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Somnolence
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0
Sciatica
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0
Ivth Nerve Paralysis
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Blood and lymphatic system disorders
Increased Tendency To Bruise
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0
Ear and labyrinth disorders
Tinnitus
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0
Eye disorders
Eczema Eyelids
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Dry Eye
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Dacryoadenitis Acquired
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Eye Pain
subjects affected / exposed	1 / 14 (7.14%)	1 / 13 (7.69%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0
Ocular Hyperaemia
subjects affected / exposed	0 / 14 (0.00%)	0 / 13 (0.00%)	0 / 10 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	1
Lacrimation Increased
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Lacrimal Gland Enlargement
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Gastrointestinal disorders
Abdominal Discomfort
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences all number	0	1	1	0
Abdominal Distension
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Abdominal Pain Lower
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences all number	0	1	1	0
Abdominal Pain Upper
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Constipation
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Diarrhoea
subjects affected / exposed	6 / 14 (42.86%)	5 / 13 (38.46%)	4 / 10 (40.00%)	0 / 3 (0.00%)
occurrences all number	10	5	4	0
Dry Mouth
subjects affected / exposed	3 / 14 (21.43%)	1 / 13 (7.69%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences all number	3	1	1	0
Dyspepsia
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Gastrooesophageal Reflux Disease
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences all number	0	1	1	0
Glossodynia
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Vomiting
subjects affected / exposed	1 / 14 (7.14%)	1 / 13 (7.69%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences all number	1	1	1	0
Steatorrhoea
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Parotid Gland Enlargement
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0
Nausea
subjects affected / exposed	2 / 14 (14.29%)	2 / 13 (15.38%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences all number	2	2	1	0
Abdominal Pain
subjects affected / exposed	2 / 14 (14.29%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	4	0	0	0
Hepatobiliary disorders
Hypertransaminasaemia
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Hepatitis Cholestatic
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Skin and subcutaneous tissue disorders
Acute Febrile Neutrophilic Dermatosis
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Alopecia
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences all number	0	1	1	0
Dermatitis
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Dermatitis Contact
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0
Eczema
subjects affected / exposed	2 / 14 (14.29%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	3	0	0	0
Lichen Planus
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0
Night Sweats
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Papule
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Pruritus
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Rash
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	2	0	0
Skin Mass
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Urticaria
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Renal and urinary disorders
Renal Cyst
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Haematuria
subjects affected / exposed	2 / 14 (14.29%)	1 / 13 (7.69%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	2	1	0	0
Urinary Retention
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 14 (7.14%)	2 / 13 (15.38%)	2 / 10 (20.00%)	0 / 3 (0.00%)
occurrences all number	1	5	4	0
Flank Pain
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences all number	0	1	1	0
Muscle Spasms
subjects affected / exposed	0 / 14 (0.00%)	0 / 13 (0.00%)	0 / 10 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	1
Musculoskeletal Stiffness
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0
Neck Pain
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences all number	0	1	1	0
Infections and infestations
Vulval Abscess
subjects affected / exposed	0 / 14 (0.00%)	0 / 13 (0.00%)	0 / 10 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	1
Urinary Tract Infection
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Upper Respiratory Tract Infection
subjects affected / exposed	0 / 14 (0.00%)	2 / 13 (15.38%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences all number	0	2	1	0
Sinusitis
subjects affected / exposed	2 / 14 (14.29%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	4	0	0	0
Respiratory Tract Infection
subjects affected / exposed	2 / 14 (14.29%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	2	0	0	0
Pneumonia Bacterial
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 14 (0.00%)	1 / 13 (7.69%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0
Laryngitis
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Covid-19
subjects affected / exposed	2 / 14 (14.29%)	3 / 13 (23.08%)	1 / 10 (10.00%)	0 / 3 (0.00%)
occurrences all number	2	3	1	0
Metabolism and nutrition disorders
Gout
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0
Malnutrition
subjects affected / exposed	1 / 14 (7.14%)	0 / 13 (0.00%)	0 / 10 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

15 Apr 2021

Removal of inclusion criteria and secondary efficacy endpoint. Addition of exclusion criteria. Improvement of operational feasibility in case of regional or national emergency such as coronavirus disease pandemic. Visit window updated to allow timely and complete Data Safety Monitoring Committee evaluations. Primary endpoint definition clarified. Exploratory objectives were added.

14 Mar 2022

Contents from of Clinical Study Protocol Version 3.1 (Canada only,18 November 2020) were consolidated with Amended Clinical Study Protocol 05 (United States only, 15 April 2021) under a single global protocol. Additional changes were intended to clarify and simplify description of overall study design and plan. Safety information from the rilzabrutinib development program and include benefit-risk information to align with Investigator Brochure version 12 (14 June 2021) were updated, exclusion criteria and stopping rules for elevated liver transaminases were modified and added section on adverse events of special interest to align with Sanofi protocol standards. Change in shape and color of rilzabrutinib tablets described.

14 Sep 2022

Primary objective was changed to address a greater unmet medical need than induction of response. Background information was updated to align with the Investigator’s Brochure Edition 13 (15 August 2022). The inclusion and exclusion criteria were updated to align with other rilzabrutinib clinical trial protocols. Study synopsis was simplified to conform to the Sanofi protocol template.

23 Feb 2023

The primary reason for this amendment was to incorporate feedback from health authorities as well as other clarifications deemed necessary by the Sponsor.

20 Feb 2024

The primary reasons for this amendment were to clarify temporal aspects of statistical considerations and include uveitis as an important potential risk.

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: An open label, two-arm, Phase 2a study to evaluate the effect of rilzabrutinib (PRN1008/SAR444671) on safety and disease activity in participants with IgG4-related disease

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Induction Treatment Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), TEAEs Leading to Discontinuation and Possible Glucocorticoid-Related TEAEs

Primary: Induction Treatment Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), TEAEs Leading to Discontinuation and Possible Glucocorticoid-Related TEAEs

Primary: Main + Maintenance Treatment Period: Number of Participants With Treatment-Emergent Adverse Events, Treatment-Emergent Serious Adverse Events, TEAEs Leading to Discontinuation and Possible Glucocorticoid-Related TEAEs

Primary: Main + Maintenance Treatment Period: Number of Participants With Treatment-Emergent Adverse Events, Treatment-Emergent Serious Adverse Events, TEAEs Leading to Discontinuation and Possible Glucocorticoid-Related TEAEs

Primary: Induction Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities (PCSAs) for Vital Signs

Primary: Induction Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities (PCSAs) for Vital Signs

Primary: Main + Maintenance Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Vital Signs

Primary: Main + Maintenance Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Vital Signs

Primary: Induction Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Hematology and Coagulation Parameters

Primary: Induction Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Hematology and Coagulation Parameters

Primary: Main + Maintenance Treatment Period:Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Hematology and Coagulation Parameters

Primary: Main + Maintenance Treatment Period:Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Hematology and Coagulation Parameters

Primary: Induction Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Chemistry Parameters

Primary: Induction Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Chemistry Parameters

Primary: Main + Maintenance Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Chemistry Parameters

Primary: Main + Maintenance Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Chemistry Parameters

Primary: Induction Treatment Period:Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Urinalysis

Primary: Induction Treatment Period:Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Urinalysis

Primary: Main + Maintenance Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Urinalysis

Primary: Main + Maintenance Treatment Period: Number of Participants With Potentially Clinically Significant Abnormalities for Clinical Laboratory Tests: Urinalysis

Primary: Percentage of Participants Without Disease Flare Following the First Dose of Rilzabrutinib

Primary: Percentage of Participants Without Disease Flare Following the First Dose of Rilzabrutinib

Secondary: Percentage of Participants With Reduction From Baseline Immunoglobulin G Subclass 4-Related Disease Responder Index Activity Score by >=2 Points Over Time

Secondary: Percentage of Participants With Reduction From Baseline Immunoglobulin G Subclass 4-Related Disease Responder Index Activity Score by >=2 Points Over Time

Secondary: Percentage of Participants With Reduction From Baseline Immunoglobulin G4-Related Disease Responder Index Activity Score=0 Over Time

Secondary: Percentage of Participants With Reduction From Baseline Immunoglobulin G4-Related Disease Responder Index Activity Score=0 Over Time

Secondary: Change From Baseline in Immunoglobulin G4-Related Disease Responder Index Over Time

Secondary: Change From Baseline in Immunoglobulin G4-Related Disease Responder Index Over Time

Secondary: Change From Baseline in Immunoglobulin G4-Related Disease Damage Over Time

Secondary: Change From Baseline in Immunoglobulin G4-Related Disease Damage Over Time

Secondary: Change From Baseline of Each Subclass of the Following Serological Markers: IgG4, IgG1, IgG, IgM, Complement C3 and C4 at Week 52

Secondary: Change From Baseline of Each Subclass of the Following Serological Markers: IgG4, IgG1, IgG, IgM, Complement C3 and C4 at Week 52

Secondary: Change From Baseline of Each Subclass of the Following Serological Marker: IgE at Week 52

Secondary: Change From Baseline of Each Subclass of the Following Serological Marker: IgE at Week 52

Secondary: Percentage of Participants who Achieved a Reduction in Baseline Serum Immunoglobulin G Subclass 4 Level of 10% Over Time

Secondary: Percentage of Participants who Achieved a Reduction in Baseline Serum Immunoglobulin G Subclass 4 Level of 10% Over Time

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
An open label, two-arm, Phase 2a study to evaluate the effect of rilzabrutinib (PRN1008/SAR444671) on safety and disease activity in participants with IgG4-related disease