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Clinical Trial Results:
A Phase 2, Multicenter, Double-Blind, Parallel Group Long Term Extension Study in Rheumatoid Arthritis Subjects Who Have Completed a Preceding Phase 2 Randomized Controlled Trial with ABBV-105 Given Alone or in Combination with Upadacitinib (ABBV-599)

Summary
EudraCT number	2018-002306-31
Trial protocol	BE HU GB ES
Global end of trial date	09 Sep 2020

Results information
Results version number	v1(current)
This version publication date	25 Aug 2021
First version publication date	25 Aug 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

M16-763

ISRCTN number

US NCT number

NCT03823378

WHO universal trial number (UTN)

Sponsor organisation name

AbbVie

Sponsor organisation address

AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6-4UB

Public contact

Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com

Scientific contact

Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.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

09 Sep 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

09 Sep 2020

Was the trial ended prematurely?

Yes

Main objective of the trial

This was a Phase 2, double-blind, multicenter, long-term extension (LTE) study to assess the safety, tolerability, and efficacy of 3 doses of ABBV-105 (elsubrutinib [ELS] 5 mg, 20 mg, and 60 mg) and ABBV-599 (ELS 60 mg and upadacitinib [UPA] 15 mg) in adults with active rheumatoid arthritis with inadequate response or intolerance to biologic disease-modifying antirheumatic drugs (bDMARDs). Participants who successfully completed treatment in the feeder Study M16-063 (NCT03682705 ), a Phase 2 dose exploratory study, were eligible to participate in this study. Those who met eligibility criteria and entered this study receiving ELS, ABBV-599, or UPA from Study M16-063 continued on their previously assigned treatment through termination of this study. Participants originally randomized to placebo in Study M16-063 rolled over to ABBV-599 in a blinded fashion in this study.

Protection of trial subjects

Subjects or their legally authorized representative must have voluntarily signed and dated an informed consent, approved by an independent ethics committee (IEC)/institutional review board (IRB), prior to the initiation of any screening or study-specific procedures.

Background therapy

Evidence for comparator

Actual start date of recruitment

13 May 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 1

Country: Number of subjects enrolled

Canada: 6

Country: Number of subjects enrolled

Czechia: 17

Country: Number of subjects enrolled

Hungary: 29

Country: Number of subjects enrolled

Poland: 22

Country: Number of subjects enrolled

Spain: 21

Country: Number of subjects enrolled

United Kingdom: 1

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

Screening details

All randomized participants

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Monitor, Assessor, Subject

Are arms mutually exclusive

Yes

ABBV-599 in M16-063/ABBV-599 in M16-763

Arm description

60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks

Arm type

Experimental

Investigational medicinal product name

Elsubrutinib

Investigational medicinal product code

Other name

ABBV-105

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Elsubrutinib capsule will be administered orally.

Investigational medicinal product name

Upadacitinib

Investigational medicinal product code

Other name

ABT-494

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Upadacitinib tablet will be administered orally.

ABBV-105 60 mg/UPA placebo

Arm description

60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks

Arm type

Experimental

Investigational medicinal product name

Elsubrutinib

Investigational medicinal product code

Other name

ABBV-105

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Elsubrutinib capsule will be administered orally.

Investigational medicinal product name

Placebo for upadacitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Upadacitinib placebo tablet will be administered orally.

ABBV-105 20 mg/UPA placebo

Arm description

20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks

Arm type

Experimental

Investigational medicinal product name

Elsubrutinib

Investigational medicinal product code

Other name

ABBV-105

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Elsubrutinib capsule will be administered orally.

Investigational medicinal product name

Placebo for upadacitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Upadacitinib placebo tablet will be administered orally.

ABBV-105 5 mg/UPA placebo

Arm description

5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks

Arm type

Experimental

Investigational medicinal product name

Elsubrutinib

Investigational medicinal product code

Other name

ABBV-105

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Elsubrutinib capsule will be administered orally.

Investigational medicinal product name

Placebo for upadacitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Upadacitinib placebo tablet will be administered orally.

UPA 15 mg/ABBV-105 placebo

Arm description

15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks

Arm type

Experimental

Investigational medicinal product name

Upadacitinib

Investigational medicinal product code

Other name

ABT-494

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Upadacitinib tablet will be administered orally.

Investigational medicinal product name

Placebo for elsubrutinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Placebo capsule for elsubrutinib will be administered orally.

Placebo in M16-063/ABBV-599 in M16-763

Arm description

Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763

Arm type

Experimental

Investigational medicinal product name

Elsubrutinib

Investigational medicinal product code

Other name

ABBV-105

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Elsubrutinib capsule will be administered orally.

Investigational medicinal product name

Upadacitinib

Investigational medicinal product code

Other name

ABT-494

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Upadacitinib tablet will be administered orally.

Number of subjects in period 1	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Started	28	16	12	12	20	9
Completed	7	0	2	2	2	1
Not completed	21	16	10	10	18	8
Adverse event, non-fatal	2	2	-	-	-	-
Other, not specified	19	12	6	8	17	7
Lost to follow-up	-	1	-	-	1	-
Withdrawal by subject	-	1	4	2	-	1

Baseline characteristics

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Reporting group title

ABBV-599 in M16-063/ABBV-599 in M16-763

Reporting group description

60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks

Reporting group title

ABBV-105 60 mg/UPA placebo

Reporting group description

60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks

Reporting group title

ABBV-105 20 mg/UPA placebo

Reporting group description

20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks

Reporting group title

ABBV-105 5 mg/UPA placebo

Reporting group description

5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks

Reporting group title

UPA 15 mg/ABBV-105 placebo

Reporting group description

15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks

Reporting group title

Placebo in M16-063/ABBV-599 in M16-763

Reporting group description

Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763

Reporting group values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763	Total
Number of subjects	28	16	12	12	20	9	97
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	57.5 ( 12.64 )	58.6 ( 8.75 )	58.5 ( 12.07 )	54.5 ( 12.21 )	61.7 ( 8.99 )	59.4 ( 9.48 )	-
Gender categorical
Units: Subjects
Female	18	14	12	8	18	7	77
Male	10	2	0	4	2	2	20

End points

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Reporting group title

ABBV-599 in M16-063/ABBV-599 in M16-763

Reporting group description

60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks

Reporting group title

ABBV-105 60 mg/UPA placebo

Reporting group description

60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks

Reporting group title

ABBV-105 20 mg/UPA placebo

Reporting group description

20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks

Reporting group title

ABBV-105 5 mg/UPA placebo

Reporting group description

5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks

Reporting group title

UPA 15 mg/ABBV-105 placebo

Reporting group description

15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks

Reporting group title

Placebo in M16-063/ABBV-599 in M16-763

Reporting group description

Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763

Primary: Number of Participants with Adverse Events (AEs)

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End point title

Number of Participants with Adverse Events (AEs) ^[1]

End point description

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug as either having a reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug.

End point type

Primary

End point timeframe

On or after the first dose of study drug in Study M16-763, and up to 30 days after the last dose of study drug in Study M16-763, up to 52 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: Descriptive data are summarized for this end point per protocol.

End point values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Number of subjects analysed	28 ^[2]	16 ^[3]	12 ^[4]	12 ^[5]	20 ^[6]	9 ^[7]
Units: participants	11	10	3	5	7	3

Notes
[2] - Safety Analysis Set: those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763
[3] - Safety Analysis Set: those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763
[4] - Safety Analysis Set: those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763
[5] - Safety Analysis Set: those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763
[6] - Safety Analysis Set: those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763
[7] - Safety Analysis Set: those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763

No statistical analyses for this end point

Secondary: Change in Disease Activity Score 28 C-reactive protein [DAS28-CRP]) from Baseline of Study M16-063 at each study visit in Study M16-763

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End point title

Change in Disease Activity Score 28 C-reactive protein [DAS28-CRP]) from Baseline of Study M16-063 at each study visit in Study M16-763

End point description

The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline indicates improvement in disease activity.

End point type

Secondary

End point timeframe

Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763

End point values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Number of subjects analysed	26 ^[8]	15 ^[9]	7 ^[10]	10 ^[11]	18 ^[12]	8 ^[13]
Units: units on a scale
arithmetic mean (confidence interval 95%)
Week 18 (n= 22, 15, 7, 10, 18, 8)	-3.27 (-3.79 to -2.75)	-1.98 (-2.83 to -1.12)	-1.93 (-3.01 to -0.85)	-2.55 (-3.50 to -1.60)	-3.88 (-4.63 to -3.14)	-2.87 (-4.05 to -1.68)
Week 24 (n= 26, 13, 7, 10, 17, 7)	-3.43 (-3.90 to -2.95)	-2.62 (-3.56 to -1.68)	-2.02 (-3.18 to -0.86)	-3.20 (-4.10 to -2.30)	-4.02 (-4.62 to -3.43)	-3.61 (-4.94 to -2.28)
Week 30 (n= 22, 13, 5, 10, 16, 8)	-3.17 (-3.86 to -2.47)	-2.37 (-3.71 to -1.03)	-1.45 (-2.30 to -0.60)	-3.30 (-4.43 to -2.17)	-3.84 (-4.56 to -3.12)	-4.08 (-4.73 to -3.44)
Week 36 (n= 23, 8, 3, 10, 12, 6)	-3.45 (-4.14 to -2.77)	-3.12 (-3.99 to -2.25)	-1.63 (-2.37 to -0.89)	-3.00 (-4.17 to -1.83)	-4.15 (-5.02 to -3.29)	-3.77 (-4.79 to -2.75)
Week 48 (n= 17, 6, 3, 8, 8, 6)	-3.55 (-4.32 to -2.78)	-2.77 (-4.92 to -0.62)	-1.68 (-3.10 to -0.27)	-3.16 (-4.49 to -1.84)	-4.38 (-5.67 to -3.09)	-3.86 (-4.88 to -2.85)
Week 60 (n= 9, 2, 2, 5, 5, 4)	-4.06 (-4.88 to -3.25)	-3.21 (-22.18 to 15.75)	-2.55 (-6.90 to 1.79)	-3.41 (-4.92 to -1.89)	-4.12 (-5.43 to -2.81)	-3.69 (-5.19 to -2.19)

Notes
[8] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[9] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[10] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[11] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[12] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[13] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data

No statistical analyses for this end point

Secondary: Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein (DAS28-CRP)

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End point title

Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein (DAS28-CRP)

End point description

The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Low Disease Activity (LDA) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than or equal to 3.2.

End point type

Secondary

End point timeframe

Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763

End point values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Number of subjects analysed	27 ^[14]	15 ^[15]	9 ^[16]	10 ^[17]	18 ^[18]	8 ^[19]
Units: percentage of participants
number (confidence interval 95%)
Week 18 (n= 23, 15, 9, 10, 18, 8)	78.3 (58.10 to 90.34)	26.7 (10.90 to 51.95)	44.4 (18.88 to 73.33)	20.0 (5.67 to 50.98)	77.8 (54.79 to 91.00)	62.5 (30.57 to 86.32)
Week 24 (n= 27, 13, 9, 10, 17, 7)	77.8 (59.24 to 89.39)	53.8 (29.14 to 76.79)	44.4 (18.88 to 73.33)	50.0 (23.66 to 76.34)	88.2 (65.66 to 96.71)	85.7 (48.69 to 97.43)
Week 30 (n= 23, 13, 7, 10, 16, 8)	78.3 (58.10 to 90.34)	76.9 (49.74 to 91.82)	28.6 (8.22 to 64.11)	60.0 (31.27 to 83.18)	87.5 (63.98 to 96.50)	100 (67.56 to 100.00)
Week 36 (n= 24, 8, 4, 10, 12, 6)	87.5 (69.00 to 95.66)	87.5 (52.91 to 97.76)	25.0 (4.56 to 69.94)	40.0 (16.82 to 68.73)	91.7 (64.61 to 98.51)	100 (60.97 to 100.00)
Week 48 (n= 18, 6, 4, 8, 8, 6)	77.8 (54.79 to 91.00)	66.7 (30.00 to 90.32)	50.0 (15.00 to 85.00)	37.5 (13.68 to 69.43)	87.5 (52.91 to 97.76)	100 (60.97 to 100.00)
Week 60 (n= 9, 2, 2, 5, 5, 4)	100 (70.09 to 100.00)	50.0 (9.45 to 90.55)	100 (34.24 to 100.00)	60.0 (23.07 to 88.24)	100 (56.55 to 100.00)	75.0 (30.06 to 95.44)

Notes
[14] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[15] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[16] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[17] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[18] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[19] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data

No statistical analyses for this end point

Secondary: Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein (DAS28-CRP)

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End point title

Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein (DAS28-CRP)

End point description

The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Clinical Remission (CR) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than 2.6.

End point type

Secondary

End point timeframe

Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763

End point values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Number of subjects analysed	27 ^[20]	15 ^[21]	9 ^[22]	10 ^[23]	18 ^[24]	8 ^[25]
Units: percentage of participants
number (confidence interval 95%)
Week 18 (n= 23, 15, 9, 10, 18, 8)	56.5 (36.81 to 74.37)	20.0 (7.05 to 45.19)	11.1 (1.99 to 43.50)	20.0 (5.67 to 50.98)	77.8 (54.79 to 91.00)	50.0 (21.52 to 78.48)
Week 24 (n= 27, 13, 9, 10, 17, 7)	70.4 (51.52 to 84.15)	53.8 (29.14 to 76.79)	33.3 (12.06 to 64.58)	30.0 (10.78 to 60.32)	70.6 (46.87 to 86.72)	71.4 (35.89 to 91.78)
Week 30 (n= 23, 13, 7, 10, 16, 8)	65.2 (44.89 to 81.19)	46.2 (23.21 to 70.86)	0 (0.00 to 35.43)	40.0 (16.82 to 68.73)	87.5 (63.98 to 96.50)	100 (67.56 to 100.00)
Week 36 (n= 24, 8, 4, 10, 12, 6)	66.7 (46.71 to 82.03)	62.5 (30.57 to 86.32)	0 (0.00 to 48.99)	20.0 (5.67 to 50.98)	75.0 (46.77 to 91.11)	66.7 (30.00 to 90.32)
Week 48 (n= 18, 6, 4, 8, 8, 6)	72.2 (49.13 to 87.50)	66.7 (30.00 to 90.32)	0 (0.00 to 48.99)	25.0 (7.15 to 59.07)	62.5 (30.57 to 86.32)	83.3 (43.65 to 96.99)
Week 60 (n= 9, 2, 2, 5, 5, 4)	77.8 (45.26 to 93.68)	50.0 (9.45 to 90.55)	50.0 (9.45 to 90.55)	0 (0.00 to 43.45)	60.0 (23.07 to 88.24)	75.0 (30.06 to 95.44)

Notes
[20] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[21] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[22] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[23] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[24] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[25] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data

No statistical analyses for this end point

Secondary: Change in Clinical Disease Activity Index (CDAI) From Baseline of Study M16-063

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End point title

Change in Clinical Disease Activity Index (CDAI) From Baseline of Study M16-063

End point description

The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. A negative change from Baseline indicates improvement in disease activity.

End point type

Secondary

End point timeframe

Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763

End point values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Number of subjects analysed	26 ^[26]	15 ^[27]	7 ^[28]	9 ^[29]	17 ^[30]	8 ^[31]
Units: units on a scale
arithmetic mean (confidence interval 95%)
Week 18 (n= 22, 15, 7, 7, 17, 8)	-33.68 (-40.72 to -26.64)	-23.77 (-32.65 to -14.90)	-19.16 (-28.05 to -10.26)	-27.00 (-42.89 to -11.11)	-36.01 (-44.11 to -27.91)	-28.65 (-37.00 to -20.30)
Week 24 (n= 26, 13, 7, 9, 16, 8)	-33.47 (-39.66 to -27.27)	-27.20 (-34.18 to -20.22)	-19.84 (-30.65 to -9.03)	-35.59 (-45.25 to -25.93)	-38.27 (-45.66 to -30.88)	-32.93 (-41.70 to -24.15)
Week 30 (n= 22, 13, 5, 9, 15, 8)	-32.07 (-40.11 to -24.03)	-22.40 (-34.25 to -10.55)	-16.72 (-22.28 to -11.16)	-35.92 (-46.64 to -25.20)	-36.86 (-46.20 to -27.52)	-34.00 (-44.11 to -27.91)
Week 36 (n= 21, 8, 3, 9, 11, 6)	-35.28 (-43.23 to -27.33)	-28.86 (-36.56 to -21.16)	-19.17 (-32.10 to -6.23)	-33.99 (-47.10 to -20.88)	-38.27 (-45.66 to -30.88)	-32.92 (-41.43 to -24.40)
Week 48 (n= 17, 6, 3, 7, 8, 5)	-36.26 (-45.44 to -27.08)	-22.58 (-41.15 to -4.02)	-18.87 (-36.40 to -1.33)	-34.77 (-49.11 to -20.44)	-36.86 (-46.20 to -27.52)	-35.72 (-45.75 to -25.69)
Week 60 (n= 9, 2, 2, 4, 5, 4)	-37.99 (-49.56 to -26.41)	-29.70 (-216.48 to 157.08)	-24.95 (-78.95 to 29.05)	-37.20 (-56.11 to -18.29)	-42.20 (-52.14 to -32.26)	-34.38 (-46.14 to -22.61)

Notes
[26] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[27] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[28] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[29] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[30] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[31] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data

No statistical analyses for this end point

Secondary: Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria

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End point title

Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria

End point description

The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. Low Disease Activity (LDA) based on CDAI is defined as achieving a total CDAI score of less than or equal to 10.

End point type

Secondary

End point timeframe

Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763

End point values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Number of subjects analysed	27 ^[32]	15 ^[33]	9 ^[34]	10 ^[35]	18 ^[36]	8 ^[37]
Units: percentage of participants
number (confidence interval 95%)
Week 18 (n= 23, 15, 9, 8, 18, 8)	82.6 (62.86 to 93.02)	40.0 (19.82 to 64.25)	44.4 (18.88 to 73.33)	50.0 (21.52 to 78.48)	77.8 (54.79 to 91.00)	62.5 (30.57 to 86.32)
Week 24 (n= 27, 13, 9, 10, 17, 8)	88.9 (71.94 to 96.15)	69.2 (42.37 to 87.32)	55.6 (26.67 to 81.12)	80.0 (49.02 to 94.33)	88.2 (65.66 to 96.71)	100 (67.56 to 100.00)
Week 30 (n= 23, 13, 7, 10, 16, 8)	78.3 (58.10 to 90.34)	76.9 (49.74 to 91.82)	42.9 (15.82 to 74.95)	80.0 (49.02 to 94.33)	81.3 (56.99 to 93.41)	100 (67.56 to 100.00)
Week 36 (n= 22, 8, 4, 10, 12, 6)	86.4 (66.67 to 95.25)	87.5 (52.91 to 97.76)	75.0 (30.06 to 95.44)	70.0 (39.68 to 89.22)	83.3 (55.20 to 95.30)	100 (60.97 to 100.00)
Week 48 (n= 18, 6, 4, 8, 8, 5)	77.8 (54.79 to 91.00)	66.7 (30.00 to 90.32)	75.0 (30.06 to 95.44)	62.5 (30.57 to 86.32)	87.5 (52.91 to 97.76)	100 (56.55 to 100.00)
Week 60 (n= 9, 2, 2, 5, 5, 4)	100 (70.09 to 100.00)	50.0 (9.45 to 90.55)	100 (34.24 to 100.00)	80.0 (37.55 to 96.38)	80.0 (37.55 to 96.38)	75.0 (30.06 to 95.44)

Notes
[32] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[33] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[34] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[35] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[36] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[37] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data

No statistical analyses for this end point

Secondary: Percentage of Participants Achieving Clinical Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria

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End point title

Percentage of Participants Achieving Clinical Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria

End point description

The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. Complete Remission (CR) based on CDAI is defined as achieving a total CDAI score of less than or equal to 2.8.

End point type

Secondary

End point timeframe

Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763

End point values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Number of subjects analysed	27 ^[38]	15 ^[39]	9 ^[40]	10 ^[41]	18 ^[42]	8 ^[43]
Units: percentage of participants
arithmetic mean (confidence interval 95%)
Week 18 (n= 23, 15, 9, 8, 18, 8)	17.4 (6.98 to 37.14)	13.3 (3.74 to 37.88)	11.1 (1.99 to 43.50)	12.5 (2.24 to 47.09)	55.6 (33.72 to 75.44)	25.0 (7.15 to 59.07)
Week 24 (n= 27, 13, 9, 10. 17, 8)	29.6 (15.85 to 48.48)	23.1 (8.18 to 50.26)	11.1 (1.99 to 43.50)	10.0 (1.79 to 40.42)	58.8 (36.01 to 78.39)	50.0 (21.52 to 78.48)
Week 30 (n= 23, 13, 7, 10, 16, 8)	26.1 (12.55 to 46.47)	30.8 (12.68 to 57.63)	14.3 (2.57 to 51.31)	30.0 (10.78 to 60.32)	43.8 (23.10 to 66.82)	87.5 (52.91 to 97.76)
Week 36 (n= 22, 8, 4, 10, 12, 6)	36.4 (19.73 to 57.05)	25.0 (7.15 to 59.07)	25.0 (4.56 to 69.94)	10.0 (1.79 to 40.42)	41.7 (19.33 to 68.05)	50.0 (18.76 to 81.24)
Week 48 (n= 18, 6, 4, 8, 8, 5)	44.4 (24.56 to 66.28)	33.3 (9.68 to 70.00)	0 (0.00 to 48.99)	12.5 (2.24 to 47.09)	50.0 (21.52 to 78.48)	100 (56.55 to 100.00)
Week 60 (n= 9, 2, 2, 5, 5, 4)	33.3 (12.06 to 64.58)	50.0 (9.45 to 90.55)	50.0 (9.45 to 90.55)	20.0 (3.62 to 62.45)	60.0 (23.07 to 88.24)	50.0 (15.00 to 85.00)

Notes
[38] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[39] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[40] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[41] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[42] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[43] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data

No statistical analyses for this end point

Secondary: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response

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End point title

Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response

End point description

Participants who met the following 3 conditions for improvement from baseline of Study M16-063 were classified as meeting the American College of Rheumatology 20% response (ACR20) criteria: 1. ≥ 20% improvement in 68-tender joint count from Baseline of Study M16-063 2. ≥ 20% improvement in 66-swollen joint count from Baseline of Study M16-063 and 3. ≥ 20% improvement in at least 3 of the 5 following parameters from Baseline of Study M16-063: • Patient's Assessment of Pain (Visual Analog Scale [VAS]) • Patient’s Global Assessment of Disease Activity (PtGA) • Physician’s Global Assessment of Disease Activity (PhGA) • Health Assessment Questionnaire Disability Index (HAQ-DI) • High-sensitivity C-reactive protein (hsCRP)

End point type

Secondary

End point timeframe

Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763

End point values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Number of subjects analysed	26 ^[44]	15 ^[45]	7 ^[46]	10 ^[47]	17 ^[48]	8 ^[49]
Units: percentage of participants
number (confidence interval 95%)
Week 18 (n=22, 15, 7, 9, 17, 8)	90.9 (72.19 to 97.47)	80.0 (54.81 to 92.95)	57.1 (25.05 to 84.18)	66.7 (35.42 to 87.94)	88.2 (65.66 to 96.71)	75.0 (40.93 to 92.85)
Week 24 (n= 26, 14, 7, 9, 16, 8)	96.2 (81.11 to 99.32)	92.9 (68.53 to 98.73)	85.7 (48.69 to 97.43)	77.8 (45.26 to 93.68)	93.8 (71.67 to 98.89)	100 (67.56 to 100.00)
Week 30 (n= 22, 13, 6, 10, 16, 8)	86.4 (66.67 to 95.25)	69.2 (42.37 to 87.32)	50.0 (18.76 to 81.24)	80.0 (49.02 to 94.33)	87.5 (63.98 to 96.50)	100 (67.56 to 100.00)
Week 36 (n= 23, 8, 3, 9, 12, 6)	87.0 (67.87 to 95.46)	87.5 (52.91 to 97.76)	66.7 (20.77 to 93.85)	88.9 (56.50 to 98.01)	91.7 (64.61 to 98.51)	83.3 (43.65 to 96.99)
Week 48 (n= 17, 6, 3, 7, 8, 6)	94.1 (73.02 to 98.95)	83.3 (43.65 to 96.99)	66.7 (20.77 to 93.85)	85.7 (48.69 to 97.43)	87.5 (52.91 to 97.76)	100 (60.97 to 100.00)
Week 60 (n= 9, 2, 2, 4, 5, 4)	88.9 (56.50 to 98.01)	100 (34.24 to 100.00)	100 (34.24 to 100.00)	75.0 (30.06 to 95.44)	100 (56.55 to 100.00)	100 (51.01 to 100.00)

Notes
[44] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[45] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[46] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[47] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[48] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[49] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data

No statistical analyses for this end point

Secondary: Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response

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End point title

Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response

End point description

Participants who met the following 3 conditions for improvement from baseline of Study M16-063 were classified as meeting the American College of Rheumatology 50% response (ACR50) criteria: 1. ≥ 50% improvement in 68-tender joint count from Baseline of Study M16-063 2. ≥ 50% improvement in 66-swollen joint count from Baseline of Study M16-063 and 3. ≥ 50% improvement in at least 3 of the 5 following parameters from Baseline of Study M16-063: • Patient's Assessment of Pain (Visual Analog Scale [VAS]) • Patient’s Global Assessment of Disease Activity (PtGA) • Physician’s Global Assessment of Disease Activity (PhGA) • Health Assessment Questionnaire Disability Index (HAQ-DI) • High-sensitivity C-reactive protein (hsCRP)

End point type

Secondary

End point timeframe

Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763

End point values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Number of subjects analysed	26 ^[50]	15 ^[51]	10 ^[52]	10 ^[53]	17 ^[54]	8 ^[55]
Units: percentage of participants
number (confidence interval 95%)
Week 18 (n= 22, 15, 10, 10, 17, 8)	68.2 (47.32 to 83.64)	46.7 (24.81 to 69.88)	40.0 (16.82 to 68.73)	40.0 (16.82 to 68.73)	70.6 (46.87 to 86.72)	62.5 (30.57 to 86.32)
Week 24 (n= 26, 14, 7, 9, 16, 8)	76.9 (57.95 to 88.97)	64.3 (38.76 to 83.66)	42.9 (15.82 to 74.95)	66.7 (35.42 to 87.94)	87.5 (63.98 to 96.50)	100 (67.56 to 100.00)
Week 30 (n= 22, 13, 6, 10, 16, 8)	63.6 (42.95 to 80.27)	61.5 (35.52 to 82.29)	16.7 (3.01 to 56.35)	60.0 (31.27 to 83.18)	87.5 (63.98 to 96.50)	100 (67.56 to 100.00)
Week 36 (n= 23, 8, 3, 9, 12, 6)	82.6 (62.86 to 93.02)	62.5 (30.57 to 86.32)	33.3 (6.15 to 79.23)	66.7 (35.42 to 87.94)	75.0 (46.77 to 91.11)	66.7 (30.00 to 90.32)
Week 48 (n= 17, 6, 3, 7, 8, 6)	82.4 (58.97 to 93.81)	66.7 (30.00 to 90.32)	66.7 (20.77 to 93.85)	71.4 (35.89 to 91.78)	87.5 (52.91 to 97.76)	83.3 (43.65 to 96.99)
Week 60 (n= 9, 2, 2, 4, 5, 4)	88.9 (56.50 to 98.01)	50.0 (9.45 to 90.55)	100 (34.24 to 100.00)	75.0 (30.06 to 95.44)	100 (56.55 to 100.00)	100 (51.01 to 100.00)

Notes
[50] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[51] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[52] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[53] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[54] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[55] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data

No statistical analyses for this end point

Secondary: Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response

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End point title

Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response

End point description

Participants who met the following 3 conditions for improvement from baseline of Study M16-063 were classified as meeting the American College of Rheumatology 70% response (ACR70) criteria: 1. ≥ 70% improvement in 68-tender joint count from Baseline of Study M16-063 2. ≥ 70% improvement in 66-swollen joint count from Baseline of Study M16-063 and 3. ≥ 70% improvement in at least 3 of the 5 following parameters from Baseline of Study M16-063: • Patient's Assessment of Pain (Visual Analog Scale [VAS]) • Patient’s Global Assessment of Disease Activity (PtGA) • Physician’s Global Assessment of Disease Activity (PhGA) • Health Assessment Questionnaire Disability Index (HAQ-DI) • High-sensitivity C-reactive protein (hsCRP)

End point type

Secondary

End point timeframe

Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763

End point values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Number of subjects analysed	26 ^[56]	15 ^[57]	10 ^[58]	12 ^[59]	18 ^[60]	8 ^[61]
Units: percentage of participants
number (confidence interval 95%)
Week 18 (n= 23, 15, 10, 12, 18, 8)	47.8 (29.24 to 67.04)	33.3 (15.18 to 58.29)	20.0 (5.67 to 50.98)	25.0 (8.89 to 53.23)	55.6 (33.72 to 75.44)	37.5 (13.68 to 69.43)
Week 24 (n= 26, 14, 8, 9, 16, 8)	57.7 (38.95 to 74.46)	42.9 (21.38 to 67.41)	12.5 (2.24 to 47.09)	55.6 (26.67 to 81.12)	62.5 (38.64 to 81.52)	87.5 (52.91 to 97.76)
Week 30 (n= 22, 13, 7, 10, 16, 8)	63.6 (42.95 to 80.27)	46.2 (23.21 to 70.86)	14.3 (2.57 to 51.31)	60.0 (31.27 to 83.18)	68.8 (44.40 to 85.84)	87.5 (52.91 to 97.76)
Week 36 (n= 23, 8, 4, 9, 12, 6)	78.3 (58.10 to 90.34)	50.0 (21.52 to 78.48)	25.0 (4.56 to 69.94)	44.4 (18.88 to 73.33)	75.0 (46.77 to 91.11)	66.7 (30.00 to 90.32)
Week 48 (n= 17, 6, 4, 7, 8, 6)	58.8 (36.01 to 78.39)	50.0 (18.76 to 81.24)	25.0 (4.56 to 69.94)	42.9 (15.82 to 74.95)	75.0 (40.93 to 92.85)	83.3 (43.65 to 96.99)
Week 60 (n= 9, 2, 2, 4, 5, 4)	88.9 (56.50 to 98.01)	50.0 (9.45 to 90.55)	50.0 (9.45 to 90.55)	25.0 (4.56 to 69.94)	60.0 (23.07 to 88.24)	75.0 (30.06 to 95.44)

Notes
[56] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[57] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[58] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[59] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[60] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[61] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data

No statistical analyses for this end point

Secondary: Change in Swollen Joint Count 66 (SJC66) From Baseline of Study M16-063

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End point title

Change in Swollen Joint Count 66 (SJC66) From Baseline of Study M16-063

End point description

Sixty-six joints were assessed for swelling by physical examination. Swelling of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with swelling) to 66 (worst possible score/66 joints with swelling). Negative values indicate improvement from baseline.

End point type

Secondary

End point timeframe

Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763

End point values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Number of subjects analysed	28 ^[62]	16 ^[63]	11 ^[64]	12 ^[65]	20 ^[66]	9 ^[67]
Units: swollen joint counts
arithmetic mean (confidence interval 95%)
Week 18 (n= 28, 16, 11, 12, 20, 9)	-11.50 (-13.66 to -9.34)	-9.88 (-14.37 to -5.38)	-8.00 (-11.28 to -4.72)	-13.42 (-18.40 to -8.43)	-12.80 (-16.11 to -9.49)	-9.78 (-13.06 to -6.50)
Week 24 (n= 27, 13, 9, 10, 17, 8)	-11.37 (-13.85 to -9.49)	-10.54 (-14.25 to -6.82)	-7.67 (-10.13 to -5.21)	-15.60 (-21.14 to -10.06)	-13.24 (-16.48 to -9.99)	-10.38 (-14.22 to -6.53)
Week 30 (n= 23, 13, 7, 10, 16, 8)	-11.87 (-14.53 to -9.21)	-7.69 (-11.64 to -3.74)	-5.86 (-8.27 to -3.44)	-15.50 (-21.05 to -9.95)	-13.44 (-17.11 to -9.77)	-10.75 (-14.61 to -6.89)
Week 36 (n= 24, 8, 4, 10, 12, 6)	-12.38 (-14.84 to -9.91)	-10.13 (-13.42 to -6.83)	-7.75 (-11.73 to -3.77)	-14.60 (-21.38 to -7.82)	-14.25 (-18.71 to -9.79)	-10.50 (-14.79 to -6.21)
Week 48 (n= 18, 6, 4, 8, 8, 6)	-13.67 (-16.57 to -10.77)	-8.00 (-16.13 to 0.13)	-8.00 (-11.90 to -4.10)	-15.88 (-21.34 to -10.41)	-15.75 (-21.84 to -9.66)	-10.67 (-15.34 to -5.99)
Week 60 (n= 9, 2, 2, 5, 5, 4)	-14.44 (-17.73 to -11.16)	-12.50 (-18.85 to -6.15)	-7.50 (-39.27 to 24.27)	-15.40 (-23.66 to -7.14)	-13.00 (-20.80 to -5.20)	-11.25 (-16.00 to -6.50)

Notes
[62] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[63] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[64] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[65] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[66] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[67] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data

No statistical analyses for this end point

Secondary: Change in Tender Joint Count 68 (TJC68) From Baseline of Study M16-063

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End point title

Change in Tender Joint Count 68 (TJC68) From Baseline of Study M16-063

End point description

Sixty-eight joints were assessed for tenderness by physical examination. Pain or tenderness of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with tenderness) to 68 (worst possible score/68 joints with tenderness). Negative values indicate improvement from baseline.

End point type

Secondary

End point timeframe

Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763

End point values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Number of subjects analysed	28 ^[68]	16 ^[69]	11 ^[70]	12 ^[71]	20 ^[72]	9 ^[73]
Units: tender joint counts
arithmetic mean (confidence interval 95%)
Week 18 (n= 28, 16, 11, 12, 20, 9)	-17.29 (-20.95 to -13.62)	-12.69 (-18.77 to -6.61)	-9.82 (-13.63 to -6.01)	-14.17 (-21.70 to -6.63)	-19.75 (-25.63 to -13.87)	-10.67 (-16.21 to -5.12)
Week 24 (n= 27, 13, 9, 10, 17, 8)	-17.93 (-21.84 to -14.02)	-15.77 (-19.37 to -12.17)	-8.11 (-10.95 to -5.28)	-20.20 (-26.97 to -13.43)	-20.76 (-27.39 to -14.14)	-14.25 (-18.44 to -10.06)
Week 30 (n= 23, 13, 7, 10, 16, 8)	-16.30 (-20.32 to -12.29)	-9.54 (-18.16 to -0.92)	-4.57 (-7.29 to -1.86)	-19.80 (-27.25 to -12.35)	-20.50 (-28.45 to -12.55)	-14.88 (-18.60 to -11.15)
Week 36 (n= 24, 8, 4, 10, 12, 6)	-16.42 (-20.15 to -12.68)	-15.25 (-19.85 to -10.65)	-8.00 (-15.46 to -0.54)	-18.40 (-26.99 to -9.81)	-24.92 (-33.96 to -15.88)	-14.83 (-19.21 to -10.46)
Week 48 (n= 18, 6, 4, 8, 8, 6)	-17.33 (-21.05 to -13.61)	-12.33 (-23.09 to -1.58)	-5.50 (-14.64 to 3.64)	-18.88 (-28.63 to -9.12)	-28.88 (-41.80 to -15.95)	-15.00 (-20.10 to -9.90)
Week 60 (n= 9, 2, 2, 5, 5, 4)	-19.78 (-25.14 to -14.41)	-19.00 (-82.53 to 44.53)	-11.50 (-81.38 to 58.38)	-20.20 (-35.42 to -4.98)	-26.20 (-36.90 to -15.50)	-15.50 (-21.52 to -9.48)

Notes
[68] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[69] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[70] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[71] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[72] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[73] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data

No statistical analyses for this end point

Secondary: Change in Participant's Assessment of Pain (Visual Analog Scale [VAS]) From Baseline of Study M16-063

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End point title

Change in Participant's Assessment of Pain (Visual Analog Scale [VAS]) From Baseline of Study M16-063

End point description

Participants rated their pain on a visual analogue scale (VAS) of 0 to 100 (mm), with 0 representing no pain and 100 representing the worst possible pain. Negative values indicate improvement from baseline.

End point type

Secondary

End point timeframe

Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763

End point values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Number of subjects analysed	26 ^[74]	15 ^[75]	7 ^[76]	10 ^[77]	18 ^[78]	8 ^[79]
Units: units on a scale
arithmetic mean (confidence interval 95%)
Week 18 (n= 22, 15, 7, 10, 18, 8)	-49.68 (-62.42 to -36.94)	-34.67 (-51.73 to -17.61)	-25.57 (-56.51 to 5.37)	-32.50 (-53.25 to -11.75)	-56.17 (-72.40 to -39.93)	-47.88 (-76.92 to -18.83)
Week 24 (n= 26, 14, 7, 10, 17, 8)	-45.46 (-58.31 to -32.61)	-48.36 (-60.60 to -36.11)	-29.43 (-50.47 to -8.39)	-42.00 (-61.74 to -22.26)	-57.76 (-73.67 to -41.86)	-59.38 (-80.35 to -38.40)
Week 30 (n= 22, 13, 5, 10, 16, 8)	-48.18 (-61.90 to -34.46)	-40.62 (-63.40 to -17.83)	-20.00 (-48.48 to 8.48)	-45.90 (-70.64 to -21.16)	-53.63 (-71.19 to -36.06)	-60.25 (-80.74 to -39.76)
Week 36 (n= 23, 8, 3, 10, 12, 6)	-49.22 (-61.84 to -36.59)	-47.13 (-72.05 to -22.20)	-25.67 (-120.27 to 68.94)	-46.70 (-63.40 to -30.00)	-58.83 (-80.69 to -36.98)	-54.83 (-90.68 to -18.98)
Week 48 (n= 17, 6, 3, 8, 8, 6)	-60.06 (-72.78 to -47.34)	-49.00 (-72.85 to -25.15)	-35.00 (-69.15 to -0.85)	-56.13 (-82.80 to -29.45)	-58.75 (-82.80 to -34.70)	-61.50 (-94.46 to -28.54)
Week 60 (n= 9, 2, 2, 5, 5, 4)	-54.67 (-77.99 to -31.34)	-52.00 (-522.13 to 418.13)	-45.50 (-140.80 to 49.80)	-58.80 (-73.74 to -43.86)	-61.00 (-88.13 to -33.87)	-55.00 (-100.36 to -9.64)

Notes
[74] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[75] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[76] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[77] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[78] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[79] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data

No statistical analyses for this end point

Secondary: Change in Patient's Global Assessment of Disease Activity (PtGA) From Baseline of Study M16-063

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End point title

Change in Patient's Global Assessment of Disease Activity (PtGA) From Baseline of Study M16-063

End point description

Participants rated their disease activity for the past 24 hours using a Patient’s Global Assessment of Disease Activity Global visual analogue scale (VAS). The range is 0 to 100 mm, with 0 representing no disease activity and 100 representing severe disease activity. Negative values indicate improvement from baseline.

End point type

Secondary

End point timeframe

Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763

End point values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Number of subjects analysed	26 ^[80]	15 ^[81]	7 ^[82]	10 ^[83]	18 ^[84]	8 ^[85]
Units: units on a scale
arithmetic mean (confidence interval 95%)
Week 18 (n= 22, 15, 7, 10. 18, 8)	-45.18 (-58.36 to -32.00)	-34.07 (-50.11 to -18.03)	-28.57 (-61.69 to 4.55)	-35.70 (-56.96 to -14.44)	-56.56 (-72.18 to -40.93)	-40.13 (-67.21 to -13.04)
Week 24 (n= 26, 14, 7, 10, 17, 8)	-48.62 (-59.37 to -37.87)	-45.93 (-60.14 to -31.72)	-33.29 (-59.62 to -6.95)	-45.20 (-61.30 to -29.10)	-62.47 (-76.09 to -48.85)	-58.13 (-74.96 to -41.29)
Week 30 (n= 22, 13, 5, 10, 16, 8)	-46.18 (-60.77 to -31.60)	-39.69 (-61.63 to -17.76)	-21.40 (-57.54 to 14.74)	-45.20 (-67.27 to -23.13)	-56.31 (-71.70 to -40.92)	-57.75 (-75.80 to -39.70)
Week 36 (n= 23, 8, 3, 10, 12, 6)	-51.70 (-64.00 to -39.39)	-48.63 (-73.95 to -23.30)	-31.67 (-141.65 to 78.32)	-46.20 (-64.52 to -27.88)	-61.00 (-81.17 to -40.83)	-53.33 (-84.24 to -22.42)
Week 48 (n= 17, 6, 3, 8, 8, 6)	-54.24 (-69.66 to -38.81)	-44.00 (-71.07 to -16.93)	-38.67 (-88.62 to 11.28)	-53.13 (-76.82 to -29.43)	-60.75 (-84.13 to -37.37)	-56.67 (-84.14 to -29.19)
Week 60 (n= 9, 2, 2, 5, 5, 4)	-56.67 (-83.18 to -30.16)	-56.00 (-462.60 to 350.60)	-54.50 (-226.03 to 117.03)	-54.60 (-70.61 to -38.59)	-59.80 (-96.50 to -23.10)	-57.00 (-87.75 to -26.25)

Notes
[80] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[81] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[82] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[83] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[84] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[85] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data

No statistical analyses for this end point

Secondary: Change in Physician's Global Assessment of Disease Activity (PhGA) From Baseline of Study M16-063

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End point title

Change in Physician's Global Assessment of Disease Activity (PhGA) From Baseline of Study M16-063

End point description

The physician assessed a participant’s disease activity at the time of the visit using a Physician's Global Assessment of Disease visual analogue scale (VAS). The range is 0 to 100 mm, with 0 representing no disease activity and 100 representing severe disease activity. Negative values indicate improvement from baseline.

End point type

Secondary

End point timeframe

Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763

End point values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Number of subjects analysed	27 ^[86]	15 ^[87]	7 ^[88]	9 ^[89]	17 ^[90]	8 ^[91]
Units: units on a scale
arithmetic mean (confidence interval 95%)
Week 18 (n= 23, 15, 7, 7, 17, 8)	-57.22 (-65.56 to -48.87)	-41.00 (-53.42 to -28.58)	-33.00 (-61.23 to -4.77)	-35.00 (-59.98 to -10.02)	-59.06 (-69.39 to -48.72)	-55.13 (-82.03 to -28.22)
Week 24 (n= 27, 14, 7, 9, 16, 8)	-57.93 (-65.61 to -50.25)	-48.36 (-60.05 to -36.66)	-39.43 (-70.88 to -7.98)	-50.89 (-68.36 to -33.42)	-61.19 (-71.90 to -50.47)	-62.38 (-77.73 to -47.02)
Week 30 (n= 23, 13, 5, 9, 15, 8)	-55.04 (-64.27 to -45.82)	-41.23 (-57.85 to -24.61)	-41.80 (-60.33 to -23.27)	-54.78 (-71.11 to -38.45)	-56.20 (-73.22 to -39.18)	-63.50 (-79.15 to -47.85)
Week 36 (n= 22, 8, 3, 9, 11, 6)	-57.55 (-66.96 to -48.13)	-53.75 (-70.49 to -37.01)	-60.00 (-112.58 to -7.42)	-54.78 (-73.97 to -35.58)	-68.45 (-81.66 to -55.25)	-65.83 (-89.60 to -42.06)
Week 48 (n= 18, 6, 3, 7, 8, 5)	-56.39 (-71.53 to -41.24)	-36.83 (-75.18 to 1.52)	-56.67 (-93.29 to -20.04)	-57.14 (-80.22 to -34.07)	-66.13 (-82.33 to -49.92)	-66.40 (-89.67 to -43.13)
Week 60 (n= 9, 2, 2, 4, 5, 4)	-64.33 (-79.18 to -49.48)	-56.00 (-437.19 to 325.19)	-65.00 (-141.24 to 11.24)	-61.50 (-88.83 to -34.17)	-60.00 (-88.34 to -31.66)	-56.75 (-87.94 to -25.56)

Notes
[86] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[87] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[88] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[89] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[90] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[91] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data

No statistical analyses for this end point

Secondary: Change in Health Assessment Questionnaire Disability Index (HAQ-DI) From Baseline of Study M16-063

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End point title

Change in Health Assessment Questionnaire Disability Index (HAQ-DI) From Baseline of Study M16-063

End point description

The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from baseline in the overall score indicates improvement.

End point type

Secondary

End point timeframe

Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763

End point values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Number of subjects analysed	25 ^[92]	15 ^[93]	7 ^[94]	10 ^[95]	17 ^[96]	8 ^[97]
Units: units on a scale
arithmetic mean (confidence interval 95%)
Week 18 (n= 22, 15, 7, 10, 17, 8)	-0.57 (-0.84 to -0.29)	-0.49 (-0.84 to -0.14)	-0.61 (-1.27 to 0.06)	-0.61 (-1.04 to -0.19)	-0.85 (-1.21 to -0.50)	-0.47 (-0.77 to -0.17)
Week 24 (n= 25, 14, 7, 10, 16, 8)	-0.59 (-0.81 to -0.36)	-0.46 (-0.80 to -0.12)	-0.57 (-1.24 to 0.09)	-0.54 (-0.98 to -0.09)	-0.59 (-0.94 to -0.25)	-0.78 (-1.29 to -0.27)
Week 30 (n= 22, 13, 5, 10, 15, 8)	-0.64 (-0.91 to -0.36)	-0.45 (-0.93 to 0.03)	-0.15 (-0.45 to 0.15)	-0.51 (-0.94 to -0.09)	-0.73 (-1.10 to -0.35)	-0.75 (-1.17 to -0.33)
Week 36 (n= 23, 8, 3, 10, 11, 6)	-0.67 (-0.95 to -0.38)	-0.70 (-1.45 to 0.05)	-0.33 (-0.81 to 0.14)	-0.30 (-0.70 to 0.10)	-0.51 (-0.94 to -0.09)	-0.56 (-1.05 to -0.07)
Week 48 (n= 17, 6, 3, 8, 8, 6)	-0.70 (-1.06 to -0.34)	-0.63 (-1.76 to 0.51)	-0.29 (-0.65 to 0.07)	-0.42 (-0.90 to 0.06)	-0.39 (-0.83 to 0.05)	-0.71 (-1.17 to -0.25)
Week 60 (n= 9, 2, 2, 5, 5, 4)	-0.78 (-1.22 to -0.34)	-0.75 (-13.46 to 11.96)	-0.31 (-4.28 to 3.66)	-0.58 (-1.30 to 0.15)	-0.48 (-1.77 to 0.82)	-0.72 (-1.61 to 0.18)

Notes
[92] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[93] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[94] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[95] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[96] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[97] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data

No statistical analyses for this end point

Secondary: Change in High-Sensitivity C-Reactive Protein (Hs-CRP) From Baseline of Study M16-063

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End point title

Change in High-Sensitivity C-Reactive Protein (Hs-CRP) From Baseline of Study M16-063

End point description

C-reactive protein is a blood test marker for inflammation in the body, and levels rise in response to inflammation. A negative change from baseline indicates improvement.

End point type

Secondary

End point timeframe

Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763

End point values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Number of subjects analysed	28 ^[98]	16 ^[99]	11 ^[100]	12 ^[101]	20 ^[102]	9 ^[103]
Units: mg/L
arithmetic mean (confidence interval 95%)
Week 18 (n= 28, 16, 11, 12, 20, 9)	-16.04 (-24.13 to -7.95)	5.34 (-9.84 to 20.53)	-0.96 (-6.20 to 4.28)	-14.85 (-34.27 to 4.57)	-11.48 (-16.88 to -6.07)	-10.00 (-28.36 to 8.35)
Week 24 (n= 27, 14, 9, 10, 17, 7)	-15.08 (-23.26 to -6.90)	-0.20 (-15.16 to 14.76)	-2.18 (-4.30 to -0.06)	-15.09 (-38.53 to 8.34)	-9.48 (-15.35 to -3.60)	-13.16 (-32.31 to 5.99)
Week 30 (n= 23, 13, 7, 10, 16, 8)	-16.61 (-27.35 to -5.88)	-6.00 (-24.37 to 12.36)	-1.66 (-4.91 to 1.59)	-17.11 (-44.18 to 9.95)	-9.55 (-14.24 to -4.85)	-16.22 (-28.83 to -3.61)
Week 36 (n= 24, 8, 4, 10, 12, 6)	-13.88 (-23.43 to -4.32)	-12.43 (-27.58 to 2.73)	-1.58 (-11.33 to 8.18)	-13.61 (-34.50 to 7.28)	-7.76 (-13.95 to -1.56)	-18.34 (-37.30 to 0.62)
Week 48 (n= 18, 6, 4, 8, 8, 6)	-16.41 (-28.14 to -4.69)	-18.38 (-50.37 to 13.60)	-5.99 (-17.43 to 5.45)	-20.18 (-49.36 to 9.00)	-7.22 (-14.57 to 0.14)	-18.30 (-36.16 to -0.44)
Week 60 (n= 9, 2, 2, 5, 5, 4)	-25.69 (-45.41 to -5.98)	-31.46 (-288.63 to 225.71)	-3.98 (-116.05 to 108.09)	-25.58 (-67.98 to 16.83)	-3.34 (-23.18 to 16.50)	-12.47 (-33.61 to 8.67)

Notes
[98] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[99] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[100] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[101] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[102] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[103] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data

No statistical analyses for this end point

Secondary: Change in Morning Stiffness Severity From Baseline of Study M16-063

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End point title

Change in Morning Stiffness Severity From Baseline of Study M16-063

End point description

Morning stiffness severity was assessed by a numeric rating-scale (NRS). Participants rated the severity of morning stiffness during the past week from 0 to 10 with 0 representing "not severe" and 10 "very severe". Negative values indicate improvement from baseline. Values of -999 and 999 in the table below indicate that the 95% confidence interval is not calculable/estimable because the standard deviation = 0.

End point type

Secondary

End point timeframe

Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763

End point values	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Number of subjects analysed	25 ^[104]	15 ^[105]	7 ^[106]	10 ^[107]	17 ^[108]	8 ^[109]
Units: units on a scale
arithmetic mean (confidence interval 95%)
Week 18 (n= 22, 15, 7, 10, 17, 8)	-4.27 (-5.56 to -2.99)	-2.27 (-3.69 to -0.84)	-2.14 (-4.99 to 0.70)	-3.40 (-6.02 to -0.78)	-5.29 (-6.54 to -4.05)	-2.38 (-4.65 to -0.10)
Week 24 (n= 25, 14, 7, 10, 16, 8)	-4.48 (-5.52 to -3.44)	-2.64 (-3.81 to -1.47)	-3.29 (-5.89 to -0.69)	-3.70 (-5.21 to -2.19)	-4.88 (-6.43 to -3.32)	-3.50 (-5.50 to -1.50)
Week 30 (n= 22, 13, 5, 10, 15, 8)	-4.36 (-5.83 to -2.90)	-2.23 (-4.28 to -0.18)	-1.20 (-2.82 to 0.42)	-4.20 (-5.66 to -2.74)	-4.53 (-5.75 to -3.32)	-3.13 (-5.55 to -0.70)
Week 36 (n= 23, 8, 3, 10, 11, 6)	-4.43 (-5.95 to -2.92)	-3.38 (-5.74 to -1.01)	-1.00 (-5.30 to 3.30)	-4.00 (-5.39 to -2.61)	-5.55 (-6.80 to -4.29)	-3.00 (-6.18 to 0.18)
Week 48 (n= 17, 6, 3, 8, 8, 6)	-5.47 (-6.64 to -4.30)	-3.33 (-6.49 to -0.17)	-1.00 (-7.57 to 5.57)	-4.13 (-6.67 to -1.58)	-5.38 (-7.10 to -3.65)	-3.67 (-6.90 to -0.44)
Week 60 (n= 9, 2, 2, 5, 5, 4)	-4.89 (-6.54 to -3.24)	-4.50 (-23.56 to 14.56)	-3.00 (-999 to 999)	-4.40 (-6.66 to -2.14)	-4.80 (-7.19 to -2.41)	-3.00 (-5.25 to -0.75)

Notes
[104] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[105] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[106] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[107] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[108] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data
[109] - Those who completed M16-063 and rcvd ≥ 1 dose of assigned study drug in M16-763 w/ available data

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

All-cause mortality is reported from enrollment to the end of study; median time on follow-up was up to 337 days. TEAEs/SAEs were collected from the first dose in M16-763 until 30 days after last dose, up to 52 weeks.

Adverse event reporting additional description

All-cause mortality and adverse events: all participants who completed Study M16-063 and received at least one dose of assigned study drug in Study M16-763, grouped according to treatments actually received in Study M16-763

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.1

Reporting group title

ABBV-599 in M16-063/ABBV-599 in M16-763

Reporting group description

60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks

Reporting group title

ABBV-105 60 mg/UPA placebo

Reporting group description

60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks

Reporting group title

ABBV-105 20 mg/UPA placebo

Reporting group description

20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks

Reporting group title

ABBV-105 5 mg/UPA placebo

Reporting group description

5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks

Reporting group title

UPA 15 mg/ABBV-105 placebo

Reporting group description

15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks

Reporting group title

Placebo in M16-063/ABBV-599 in M16-763

Reporting group description

Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763

Serious adverse events	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 28 (3.57%)	0 / 16 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 20 (5.00%)	0 / 9 (0.00%)
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)
LUNG ADENOCARCINOMA
subjects affected / exposed	1 / 28 (3.57%)	0 / 16 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	1 / 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
Injury, poisoning and procedural complications
PERIPROSTHETIC FRACTURE
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 20 (5.00%)	0 / 9 (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

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

Non-serious adverse events	ABBV-599 in M16-063/ABBV-599 in M16-763	ABBV-105 60 mg/UPA placebo	ABBV-105 20 mg/UPA placebo	ABBV-105 5 mg/UPA placebo	UPA 15 mg/ABBV-105 placebo	Placebo in M16-063/ABBV-599 in M16-763
Total subjects affected by non serious adverse events
subjects affected / exposed	8 / 28 (28.57%)	10 / 16 (62.50%)	3 / 12 (25.00%)	5 / 12 (41.67%)	7 / 20 (35.00%)	3 / 9 (33.33%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	0	0	1
Vascular disorders
HYPERTENSION
subjects affected / exposed	0 / 28 (0.00%)	1 / 16 (6.25%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0	0	0
General disorders and administration site conditions
ASTHENIA
subjects affected / exposed	0 / 28 (0.00%)	1 / 16 (6.25%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0	0	0
DRUG INTOLERANCE
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 20 (5.00%)	0 / 9 (0.00%)
occurrences all number	0	0	0	0	1	0
DRUG WITHDRAWAL SYNDROME
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	0	0	1
INFLUENZA LIKE ILLNESS
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	0	0	1
NON-CARDIAC CHEST PAIN
subjects affected / exposed	0 / 28 (0.00%)	1 / 16 (6.25%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0	0	0
PYREXIA
subjects affected / exposed	0 / 28 (0.00%)	1 / 16 (6.25%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	1	0	0
Psychiatric disorders
ANXIETY
subjects affected / exposed	0 / 28 (0.00%)	1 / 16 (6.25%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0	0	0
DEPRESSION
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	0	0	1
Investigations
URINE ANALYSIS ABNORMAL
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0	0	0
Injury, poisoning and procedural complications
FALL
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 20 (5.00%)	0 / 9 (0.00%)
occurrences all number	0	0	0	0	1	0
Nervous system disorders
DIZZINESS
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	0	0	1
HEADACHE
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0	0	0
TREMOR
subjects affected / exposed	0 / 28 (0.00%)	1 / 16 (6.25%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0	0	0
Blood and lymphatic system disorders
ANAEMIA
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	0	0	1	0	0
MICROCYTIC ANAEMIA
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	0	0	1	0	0
Gastrointestinal disorders
ABDOMINAL PAIN
subjects affected / exposed	0 / 28 (0.00%)	1 / 16 (6.25%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0	0	0
DIARRHOEA
subjects affected / exposed	0 / 28 (0.00%)	1 / 16 (6.25%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0	0	0
NAUSEA
subjects affected / exposed	0 / 28 (0.00%)	1 / 16 (6.25%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0	0	0
VOMITING
subjects affected / exposed	1 / 28 (3.57%)	1 / 16 (6.25%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	1	0	0	0	0
Skin and subcutaneous tissue disorders
DERMATITIS
subjects affected / exposed	0 / 28 (0.00%)	1 / 16 (6.25%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0	0	0
Renal and urinary disorders
RENAL CYST
subjects affected / exposed	1 / 28 (3.57%)	0 / 16 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 20 (5.00%)	0 / 9 (0.00%)
occurrences all number	1	0	0	0	1	0
Musculoskeletal and connective tissue disorders
JOINT SWELLING
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	0	0	1	0	0
RHEUMATOID ARTHRITIS
subjects affected / exposed	2 / 28 (7.14%)	4 / 16 (25.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	2	4	0	0	0	0
Infections and infestations
BRONCHITIS
subjects affected / exposed	1 / 28 (3.57%)	1 / 16 (6.25%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 20 (5.00%)	0 / 9 (0.00%)
occurrences all number	1	1	0	0	1	0
EAR INFECTION
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 20 (5.00%)	0 / 9 (0.00%)
occurrences all number	0	0	0	0	1	0
GASTROENTERITIS
subjects affected / exposed	0 / 28 (0.00%)	1 / 16 (6.25%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0	0	0
NASOPHARYNGITIS
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 20 (5.00%)	0 / 9 (0.00%)
occurrences all number	0	0	0	0	1	0
ORAL CANDIDIASIS
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	0	0	1	0	0
RESPIRATORY TRACT INFECTION VIRAL
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 20 (5.00%)	0 / 9 (0.00%)
occurrences all number	0	0	0	0	1	0
TOOTH INFECTION
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 20 (5.00%)	0 / 9 (0.00%)
occurrences all number	0	0	0	0	1	0
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	3 / 28 (10.71%)	1 / 16 (6.25%)	0 / 12 (0.00%)	1 / 12 (8.33%)	1 / 20 (5.00%)	0 / 9 (0.00%)
occurrences all number	3	1	0	2	1	0
URETHRITIS
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0	0	0
URINARY TRACT INFECTION
subjects affected / exposed	1 / 28 (3.57%)	0 / 16 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	2 / 20 (10.00%)	1 / 9 (11.11%)
occurrences all number	1	0	0	0	2	1
Metabolism and nutrition disorders
DIABETES MELLITUS
subjects affected / exposed	0 / 28 (0.00%)	1 / 16 (6.25%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0	0	0
HYPERGLYCAEMIA
subjects affected / exposed	0 / 28 (0.00%)	0 / 16 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 20 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	0	0	1

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

12 Oct 2018

Version 2 -- Added the following for additional safety monitoring for potential AEs, clarification of clinical definitions, and to assure compliance with local guidelines: -- 12-lead electrocardiogram (ECG) at Weeks 12, 18, 24, 30, and 48; -- Clarification of the rationale/objective for exploratory biomarker research; -- Added contraception barrier method as a requirement per local regulations; -- Added guidance regarding unblinding in event of a medical situation requiring urgent clinical need to know randomization assignment; and -- Added information regarding subject at-home weekly temperature monitoring for assessment of serious infections

17 Jan 2019

Version 3 -- Added advisement to follow local public health guidelines for management of potential TB risk -- Added T SPOT TB test as possible test for identification of latent TB -- Added an UPA efficacy analysis set -- Added the following for additional safety monitoring for potential AEs, clarification of clinical definitions, and to assure compliance with local guidelines: -- 12-lead ECG at Weeks 12, 18, 24, 30, and 48; -- Clarification of the rationale/objective for exploratory biomarker research; -- Added contraception barrier method as a requirement per local regulations; and -- Added guidance regarding unblinding in event of a medical situation requiring urgent clinical need to know randomization assignment -- Added information regarding subject at-home weekly temperature monitoring for assessment of serious infections -- Added information regarding UPA safety data -- Clarified safety endpoints regarding Data Monitoring Committee and when the clinical trial would be discontinued -- Updated eligibility criteria to include relevant eligibility requirements from Study M16-063 applicable to Study M16-763 -- Updated efficacy endpoints and statistical analysis for efficacy to reflect that there were no primary efficacy endpoints and that no formal statistical tests would be applied -- Clarified that the use of live vaccines was to be avoided for 4 weeks after the last dose of study drug for alignment with Study M16-063

06 Feb 2020

Version 4 -- Added additional Clinical Disease Activity Index (CDAI) efficacy endpoints -- Clarified birth control practices in eligibility criteria -- Clarified study discontinuation criteria, study drug discontinuation processes, study drug dispensation instructions, and herpes zoster vaccine instructions -- Added information to clarify Safety Analysis Set parameters -- Added an All ABBV-599 efficacy analysis set (Group 7: Group 1 and Group 6 combined) -- Added an interim analysis to review long-term safety and efficacy -- Removed troponin and troponin + creatine kinase myocardial band (CKMB) testing (asymptomatic creatine phosphokinase [CPK] elevation is a known Janus kinase [JAK] inhibitor class effect) -- Removed reference to liver biopsies as there were no liver biopsies at Screening or any time during the Study

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 Phase 2, Multicenter, Double-Blind, Parallel Group Long Term Extension Study in Rheumatoid Arthritis Subjects Who Have Completed a Preceding Phase 2 Randomized Controlled Trial with ABBV-105 Given Alone or in Combination with Upadacitinib (ABBV-599)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants with Adverse Events (AEs)

Primary: Number of Participants with Adverse Events (AEs)

Secondary: Change in Disease Activity Score 28 C-reactive protein [DAS28-CRP]) from Baseline of Study M16-063 at each study visit in Study M16-763

Secondary: Change in Disease Activity Score 28 C-reactive protein [DAS28-CRP]) from Baseline of Study M16-063 at each study visit in Study M16-763

Secondary: Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein (DAS28-CRP)

Secondary: Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein (DAS28-CRP)

Secondary: Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein (DAS28-CRP)

Secondary: Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein (DAS28-CRP)

Secondary: Change in Clinical Disease Activity Index (CDAI) From Baseline of Study M16-063

Secondary: Change in Clinical Disease Activity Index (CDAI) From Baseline of Study M16-063

Secondary: Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria

Secondary: Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria

Secondary: Percentage of Participants Achieving Clinical Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria

Secondary: Percentage of Participants Achieving Clinical Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria

Secondary: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response

Secondary: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response

Secondary: Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response

Secondary: Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response

Secondary: Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response

Secondary: Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response

Secondary: Change in Swollen Joint Count 66 (SJC66) From Baseline of Study M16-063

Secondary: Change in Swollen Joint Count 66 (SJC66) From Baseline of Study M16-063

Secondary: Change in Tender Joint Count 68 (TJC68) From Baseline of Study M16-063

Secondary: Change in Tender Joint Count 68 (TJC68) From Baseline of Study M16-063

Secondary: Change in Participant's Assessment of Pain (Visual Analog Scale [VAS]) From Baseline of Study M16-063

Secondary: Change in Participant's Assessment of Pain (Visual Analog Scale [VAS]) From Baseline of Study M16-063

Secondary: Change in Patient's Global Assessment of Disease Activity (PtGA) From Baseline of Study M16-063

Secondary: Change in Patient's Global Assessment of Disease Activity (PtGA) From Baseline of Study M16-063

Secondary: Change in Physician's Global Assessment of Disease Activity (PhGA) From Baseline of Study M16-063

Secondary: Change in Physician's Global Assessment of Disease Activity (PhGA) From Baseline of Study M16-063

Secondary: Change in Health Assessment Questionnaire Disability Index (HAQ-DI) From Baseline of Study M16-063

Secondary: Change in Health Assessment Questionnaire Disability Index (HAQ-DI) From Baseline of Study M16-063

Secondary: Change in High-Sensitivity C-Reactive Protein (Hs-CRP) From Baseline of Study M16-063

Secondary: Change in High-Sensitivity C-Reactive Protein (Hs-CRP) From Baseline of Study M16-063

Secondary: Change in Morning Stiffness Severity From Baseline of Study M16-063

Secondary: Change in Morning Stiffness Severity From Baseline of Study M16-063

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2, Multicenter, Double-Blind, Parallel Group Long Term Extension Study in Rheumatoid Arthritis Subjects Who Have Completed a Preceding Phase 2 Randomized Controlled Trial with ABBV-105 Given Alone or in Combination with Upadacitinib (ABBV-599)