A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (RA)

Study Overview
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Brief Summary
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This study will assess the safety, tolerability, and efficacy of ABBV-3373 in participants with moderately to severely active rheumatoid arthritis (RA) on background methotrexate (MTX) compared with adalimumab.

Detailed Description
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This study consists of a 12-week double-blind active-controlled phase and a 12 week double-blind extension period. In the active-controlled period of the first 12 weeks of treatment, participants are randomized to receive either ABBV-3373 100 mg intravenously (IV) every other week (EOW) or adalimumab 80 mg subcutaneously (SC) EOW according to a 2:1 ratio. At Week 12, the administration of ABBV-3373 was to stop to assess the durability of the observed clinical effects up to 24 weeks. Participants randomized to ABBV-3373 were to receive placebo injections, whereas participants randomized into the adalimumab arm were to continue their 80 mg dosing.

Official Title
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A Randomized, Double-Blind, Double-Dummy, Active Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Subjects With Moderate to Severe Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis (RA)

Intervention / Treatment
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* Drug: ABBV-3373
* Drug: Placebo for ABBV-3373
* Drug: Adalimumab
* Drug: Placebo for adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has the clinical diagnosis of RA for > 3 months based on the 1987 American College of Rheumatology (ACR) classification criteria or 2010 ACR/European League against Rheumatism (EULAR) criteria. Participant meets the following disease activity criteria: >= 4 swollen joints (based on 28 joint count) and >= 4 tender joints (based on 28 joint count) at Screening and Baseline visits and disease activity score (28 joints) (DAS28) C-reactive protein (CRP) >= 3.2 at Screening. Participant has an incomplete response to methotrexate. Participants must have been on oral or parental MTX therapy >= 3 months and on a stable prescription of 15 to 25 mg/week (or >= 10 mg/week in participants intolerant of MTX at doses >= 15 mg/week) for >= 4 weeks prior to the first dose of study drug. Participant must be expected to be able to continue on stable dose of MTX for the duration of study participation. Exclusion Criteria: Participants previously exposed to adalimumab or other anti-tumor necrosis factor (TNF) biologics. Participants previously exposed to non-anti-TNF biologics or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for RA, with exception of participants exposed for less than 3 months and terminated not due to lack of efficacy or intolerability.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABBV-3373 Followed by Placebo<br>Participants will be administered with 100 mg ABBV-3373 by intravenous infusion and placebo to adalimumab by subcutaneous injection every other week for 12 weeks. After 12 weeks, participants will receive placebo to adalimumab every other week until Week 22. | Drug: ABBV-3373<br>* ABBV-3373 is administered as intravenous (IV) infusion<br>Drug: Placebo for adalimumab<br>* Placebo for adalimumab is administered as subcutaneous (SC) injection<br>|
| Experimental: Adalimumab<br>Participants will be administered with placebo to ABBV-3373 by intravenous infusion and 80 mg adalimumab by subcutaneous injection every other week for 12 weeks. After 12 weeks, participants will receive 80 mg adalimumab subcutaneously every other week until Week 22. | Drug: Placebo for ABBV-3373<br>* Placebo for ABBV-3373 is administered as IV infusion<br>Drug: Adalimumab<br>* Adalimumab is administered as subcutaneous (SC) injection<br>* Other names: Humira;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in Disease Activity Score (DAS) 28 (C-reactive Protein [CRP]) | 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 (measured on a visual analog scale [VAS] from 0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 (CRP) range from 0.96 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in Clinical Disease Activity Index (CDAI) | The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient Global Assessment of Disease Activity and Physician Global Assessment of Disease Activity both measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 76 with higher scores indicating higher disease activity. A negative change from Baseline indicates improvement in disease activity. | Baseline and Week 12 | 
| Change From Baseline in Simplified Disease Activity Index (SDAI) | The SDAI is the numerical sum of five outcome parameters: tender and swollen joint count (based on a 28-joint assessment), Patient Global Assessment of Disease Activity and Physician Global Assessment of Disease Activity both measured on a VAS from 0-10 cm and level of CRP (in mg/dL; normal < 1 mg/dL). The SDAI has a range from 0 to 86, with higher scores indicating higher disease activity. A negative change from Baseline indicates improvement in disease activity. | Baseline and Week 12 | 
| Change From Baseline to Week 12 in DAS28 (Erythrocyte Sedimentation Rate [ESR]) | The DAS28 (ESR) 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 (measured on a VAS from 0-100 mm), and ESR (in mm/hr). Scores on the DAS28 (ESR) range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline indicates improvement in disease activity. | Baseline and Week 12 | 
| Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28 (CRP) at Week 12 | 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 (measured on a VAS from 0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 (CRP) range from 0.96 to approximately 10, where higher scores indicate more disease activity. A DAS28 (CRP) score less than or equal to 3.2 indicates low disease activity. | Week 12 | 
| Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 | Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria: ≥ 50% improvement in 68-tender joint count; ≥ 50% improvement in 66-swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP). | Baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis (RA), ABBV-3373, Adalimumab