A Study to Investigate the Safety and Efficacy of ABBV-105 Alone or in Combination With Upadacitinib (ABBV-599 Combination) in Participants With Active Rheumatoid Arthritis

AbbVie

Status and phase: Completed; Phase 2

Conditions: Rheumatoid Arthritis (RA)

Treatments: Drug: Upadacitinib; Drug: Placebo for elsubrutinib; Drug: Placebo for upadacitinib; Drug: Elsubrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03682705

2018-000666-10 (EudraCT Number)

M16-063

Details and patient eligibility

About

This was a phase 2 study to evaluate the safety and efficacy of elsubrutinib (ELS) and ABBV-599 (ELS plus upadacitinib [UPA]) vs placebo on a background of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) for the treatment of signs and symptoms of rheumatoid arthritis (RA) at 12 weeks in biological disease-modifying anti-rheumatic drugs (bDMARD)-inadequate response (bDMARD-IR) or bDMARD-intolerant participants with moderately to severely active RA and to define optimal dose for further development.

Full description

This was a 12-week, randomized, double-blind, parallel-group, Phase 2, dose exploratory, multicenter study. Participants who met eligibility criteria were randomized in a 3:2:2:2:2:1 ratio to 1 of 6 treatment groups: ABBV-599 [UPA 15 mg/ELS 60 mg]); ELS 60 mg/UPA placebo; ELS 20 mg/UPA placebo; ELS 5 mg/UPA placebo; UPA 15 mg/ELS placebo; and ELS placebo/UPA placebo. The study included a 35-day maximum screening period and a 12-week treatment period with 30-day follow-up.

Enrollment: 242 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of rheumatoid arthritis (RA) for ≥ 3 months based on the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA

• Participant meets the following minimum disease activity criteria:

  • ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits
  • High-sensitivity C-reactive protein (hsCRP) ≥ 3 mg/L (central lab) at Screening Visit

• Participants must have been treated for ≥ 3 months with ≥ 1 biologic disease-modifying anti-rheumatic drug (bDMARD) therapy but continue to exhibit active RA or had to discontinue due to intolerability or toxicity, irrespective of treatment duration

• Participants must have been receiving conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) therapy ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug

• Participants must have discontinued all bDMARDs prior to the first dose of study drug

Exclusion criteria

• Participant has prior exposure to any Janus Kinase (JAK) inhibitor for greater than 2 weeks (including but not limited to upadacitinib, tofacitinib, baricitinib, and filgotinib). A washout period of ≥ 30 days is required for any JAK inhibitor prior to the first dose of study drug.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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242 participants in 6 patient groups, including a placebo group

ELS placebo/UPA placebo

Placebo Comparator group

Description:

Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks

Treatment:

Drug: Placebo for upadacitinib

Drug: Placebo for elsubrutinib

UPA 15 mg/ELS 60 mg

Experimental group

Description:

15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks

Treatment:

Drug: Elsubrutinib

Drug: Upadacitinib

ELS 60 mg/UPA placebo

Experimental group

Description:

60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks

Treatment:

Drug: Elsubrutinib

Drug: Placebo for upadacitinib

ELS 20 mg/UPA placebo

Experimental group

Description:

20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks

Treatment:

Drug: Elsubrutinib

Drug: Placebo for upadacitinib

ELS 5 mg/UPA placebo

Experimental group

Description:

5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks

Treatment:

Drug: Elsubrutinib

Drug: Placebo for upadacitinib

UPA 15 mg/ELS placebo

Experimental group

Description:

15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks

Treatment:

Drug: Placebo for elsubrutinib

Drug: Upadacitinib