A Study to Evaluate Different Targeted Therapies for Patients With Rheumatoid Arthritis

AbbVie

Status and phase: Enrolling; Phase 2

Conditions: Rheumatoid Arthritis

Treatments: Drug: Adalimumab; Drug: Lutikizumab; Drug: ABBV-848; Drug: Placebo; Drug: ABBV-8736; Drug: ABBV-701; Drug: Ravagalimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06972446

2025-520721-21-00 (Other Identifier)

M25-056

2025

Details and patient eligibility

About

Rheumatoid Arthritis (RA) is a chronic inflammatory disease causing pain, stiffness, swelling and loss of joint function. This study will evaluate the efficacy and safety of targeted therapies through a series of substudies for the treatment of moderately to severely active Rheumatoid Arthritis (RA).

This study currently includes 6 substudies evaluating different treatments in participants with RA. Substudy 1 will evaluate lutikizumab monotherapy (treatment given alone) compared to placebo (looks like the study treatment but contains no medicine). Substudy 2 will evaluate ravagalimab monotherapy compared to placebo. Substudy 3 will evaluate lutikizumab and ravagalimab combination therapy (treatments given together) compared to placebo. Substudy 4 will evaluate ABBV-8736 compared to Placebo. Substudy 5 will evaluate ABBV-701 compared to Placebo and Substudy 6 will be a proof of concept study of ABBV-848 in participants who are on a stable background of Methotrexate, with an Adalimumab reference arm. Approximately 180 participants who have failed 1 or 2 biologic/targeted synthetic disease-modifying antirheumatic drug (tsDMARD) therapies will be enrolled in the study at up to 200 sites worldwide.

There may be higher treatment burden for participants in this trial compared to their standard of care treatment without participating in this study. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Enrollment: 180 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• At any time prior to the Screening Visit, participant must have been treated for > or = 3 months with at least 1 b/tsDMARD therapy but continued to exhibit active RA, or had to discontinue due to intolerability or toxicity, irrespective of treatment duration. The maximum cap for prior use of b/tsDMARD is 2.
• Participant must be on a stable dose of methotrexate (MTX)

Exclusion criteria

• Participant is taking nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen/paracetamol, low-potency opioids (tramadol, codeine, hydrocodone, alone or in combination with acetaminophen), oral corticosteroids (equivalent to ≤ 10 mg/day of prednisone), or inhaled corticosteroids for stable medical conditions unless they have been on stable doses for ≥ 1 week prior to Baseline Visit.
• History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than rheumatoid arthritis.

Sub-study 6 specific:

• Prior exposure to any Interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor or degrader.
• Prior exposure to any biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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180 participants in 12 patient groups, including a placebo group

Substudy 1: Lutikizumab Monotherapy

Experimental group

Description:

Participants will be randomized to initially receive Lutikizumab Dose A followed by Lutikizumab Dose B

Treatment:

Drug: Lutikizumab

Substudy 1: Matching Placebo Monotherapy

Placebo Comparator group

Description:

Participants will be randomized to receive a matching placebo dose equivalent to the Lutikizumab monotherapy.

Treatment:

Drug: Placebo

Substudy 2: Ravagalimab Monotherapy

Experimental group

Description:

Participants will be randomized to receive Ravagalimab

Treatment:

Drug: Ravagalimab

Substudy 2: Matching Placebo Monotherapy

Placebo Comparator group

Description:

Participants will be randomized to receive a matching placebo dose equivalent to the Ravagalimab monotherapy

Treatment:

Drug: Placebo

SubStudy 3: Lutikizumab and Ravagalimab Combination Therapy

Experimental group

Description:

Participants will be randomized to be administered Lutikizumab and Ravagalimab doses

Treatment:

Drug: Ravagalimab

Drug: Lutikizumab

Substudy 3: Matching Placebo Combination Therapy

Placebo Comparator group

Description:

Participants will be randomized to receive matching placebo doses equivalent to the Lutikizumab and Ravagalimab combination therapy

Treatment:

Drug: Placebo

Substudy 4: Double-Blind Treatment Period

Experimental group

Description:

Participants will be randomized to receive either ABBV-8736 or matching placebo dose

Treatment:

Drug: ABBV-8736

Drug: Placebo

Substudy 4: Long Term Open-Label Extension Period

Experimental group

Description:

Participants will receive open-label ABBV-8736 monotherapy

Treatment:

Drug: ABBV-8736

Substudy 5: Double-Blind Treatment Period

Experimental group

Description:

Participants will be randomized to either receive ABBV-701 or matching placebo dose

Treatment:

Drug: ABBV-701

Drug: Placebo

Substudy 5: Long Term Open-Label Extension Period

Experimental group

Description:

Participants will receive open-label ABBV-701 monotherapy

Treatment:

Drug: ABBV-701

Substudy 6: Double-Blind Treatment Period 1

Experimental group

Description:

Participants will be randomized to either receive ABBV-848, Adalimumab or matching placebo dose

Treatment:

Drug: ABBV-848

Drug: Placebo

Drug: Adalimumab

Substudy 6: Open-Label Extension Period 2

Experimental group

Description:

Participants will receive open-label ABBV-848 monotherapy

Treatment:

Drug: ABBV-848