Study to Evaluate Adverse Events and Change in Disease Activity in Participants Between 18 to 75 Years of Age Treated With Subcutaneous (SC) Injections of ABBV-154 for Moderately to Severely Active Rheumatoid Arthritis (RA)

Study Overview
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Brief Summary
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Rheumatoid Arthritis (RA) is an inflammatory disease of the joints causing pain, stiffness, swelling and loss of joint function. This study evaluates how safe and effective ABBV-154 is in participants treated for moderately to severely active RA. Adverse events and change in the disease activity will be assessed. ABBV-154 is an investigational drug being evaluated for the treatment of RA. Study doctors place the participants in 1 of 5 treatment groups or arms, each arm receiving a different treatment. There is a 1 in 5 chance that participants will be assigned to placebo. Participants 18-75 years of age with moderate to severe RA will be enrolled. Around 425 participants will be enrolled in the study in approximately 270 sites worldwide. The study is comprised of a 12-week placebo-controlled period, a double-blind long-term extension (LTE) period 1 of 66 weeks, a LTE period 2 of 104 weeks and a follow-up visit 70 days after the last dose of the study drug. In the LTE period 1, participants in the placebo group will be re-randomized to receive ABBV-154 in 2 different doses SC every other week (eow). Other participants will remain on their previous dose and dosing regimen of ABBV-154. There may be higher treatment burden for participants in this trial compared to their standard of care. 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.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of ABBV-154 in Subjects With Moderately to Severely Active Rheumatoid Arthritis With Inadequate Response to Biologic and/or Targeted Synthetic Disease-Modifying Anti-Rheumatic Drugs (b/tsDMARDs)

Conditions
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Rheumatoid Arthritis (RA)

Intervention / Treatment
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* Drug: ABBV-154
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of rheumatoid arthritis(RA) with fulfillment of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA. Participant has >= 6 swollen joints (based on 66 joint count) and >=6 tender joints (based on 68 joint count) at baseline. Participant must have had an inadequate response to at least one prior biologic and/or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) treatment for RA. Participants must be on stable dose of methotrexate (MTX). Exclusion Criteria: - Participant discontinued prior adalimumab therapy due to intolerability or toxicity.

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: Dose A of ABBV-154<br>Participants in this group will receive dose A of ABBV-154 subcutaneously (SC) every other week (eow) for 12 weeks in the placebo-controlled period, 66 weeks in the long term extension (LTE) period 1 and 104 weeks in LTE period 2. | Drug: ABBV-154<br>* Subcutaneous Injection<br>|
| Experimental: Dose B of ABBV-154<br>Participants in this group will receive dose B of ABBV-154 SC eow for 12 weeks in the placebo-controlled period, 66 weeks in the LTE period 1 and 104 weeks in LTE period 2. | Drug: ABBV-154<br>* Subcutaneous Injection<br>|
| Experimental: Dose C of ABBV-154 EOW<br>Participants in this group will receive dose C of ABBV-154 SC eow for 12 weeks in the placebo-controlled period, 66 weeks in the LTE period 1 and 104 weeks in LTE period 2. | Drug: ABBV-154<br>* Subcutaneous Injection<br>|
| Experimental: Dose C of ABBV-154 E4W<br>Participants in this group will receive dose C of ABBV-154 SC every 4 weeks (e4w) for 12 weeks in the placebo-controlled period, 66 weeks in the LTE period 1 and 104 weeks in LTE period 2. | Drug: ABBV-154<br>* Subcutaneous Injection<br>|
| Experimental: Placebo<br>Participants in this group will receive placebo SC eow for 12 weeks in the placebo-controlled period and will be re-randomized in 1:1 ratio to receive ABBV-154 dose B or C respectively SC eow for 66 weeks in the LTE period 1 and 104 weeks in LTE period 2. | Drug: ABBV-154<br>* Subcutaneous Injection<br>Drug: Placebo<br>* Subcutaneous Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving American College of Rheumatology 50 % (ACR50) Response | 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's Global Assessment of Disease Activity measured on a Numerical Rating Scale of 0 to 10 (NRS) Patient's Global Assessment of Disease Activity (NRS) Patient's Assessment of Pain (NRS) Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP). | At 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Disease Activity Score (DAS) 28 (CRP) from Baseline | The DAS28 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 (NRS), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. | Up to 12 weeks | 
| Change in Clinical Disease Activity Index (CDAI) from Baseline | CDAI is a composite index for assessing disease activity based on the sum of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (NRS), and Physician's Global Assessment of Disease Activity (NRS). The total CDAI score ranges from 0 to 76 with higher scores indicating higher disease activity. | Up to 12 weeks | 
| Percentage of Participants Achieving American College of Rheumatology 20 % (ACR20) Response | Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria: ≥ 20% improvement in 68-tender joint count; ≥ 20% improvement in 66-swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Physician's Global Assessment of Disease Activity (NRS) Patient's Global Assessment of Disease Activity (NRS) Patient's Assessment of Pain (NRS) Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP). | At 12 weeks | 
| Percentage of Participants Achieving American College of Rheumatology 70 % (ACR70) Response | Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response criteria: ≥ 70% improvement in 68-tender joint count; ≥ 70% improvement in 66-swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Physician's Global Assessment of Disease Activity (NRS) Patient's Global Assessment of Disease Activity (NRS) Patient's Assessment of Pain (NRS) Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP). | At 12 weeks | 
| Percentage of Participants Achieving Low Disease Activity (LDA) Defined by DAS28 (CRP) <= 3.2 | Low disease activity (LDA) was defined as a DAS28 score less than or equal to 3.2. The DAS28 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 (NRS) and Physician's Global Assessment of Disease Activity (NRS), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. | At 12 weeks | 
| Percentage of Participants Achieving LDA Defined by CDAI <= 10 | Low disease activity based on CDAI is defined as a CDAI score less than or equal to 10. CDAI is a composite index for assessing disease activity based on the sum of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (NRS), and Physician's Global Assessment of Disease Activity (NRS). The total CDAI score ranges from 0 to 76 with higher scores indicating higher disease activity. | At 12 weeks | 
| Percentage of Participants Achieving Clinical Remission (CR) Defined by DAS28 (CRP) < 2.6 | Clinical remission was defined as a DAS28 (CRP) score less than 2.6. The DAS28 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 (NRS), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. | At 12 weeks | 
| Percentage of Participants Achieving CR Defined by CDAI <= 2.8 | Clinical Remission was defined by CDAI as a score less than or equal to 2.8. 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's Global Assessment of Disease Activity (NRS), and Physician's Global Assessment of Disease Activity (NRS). The total CDAI score ranges from 0 to 76 with higher scores indicating higher disease activity. | At 12 weeks | 
| Change in the Health Assessment Questionnaire Disability Index (HAQ-DI) From Baseline | The Health Assessment Questionnaire - Disability Index is a participant-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. | Up to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis (RA), ABBV-154, AIM-RA