Safety and Effectiveness of Acthar Gel in Participants With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This is a 2-part study to examine the effect of Acthar Gel in adult participants with rheumatoid arthritis (RA) with persistently active disease even after receiving two other treatments intended to modify the disease. Part 1 is an Open Label Period in which all eligible participants receive Acthar Gel for 12 weeks. After these 12 weeks of treatment with Acthar Gel, participants will be evaluated for treatment response using the DAS28-ESR. Participants who have achieved low disease activity (LDA) will enter a double-blind randomized maintenance period (Part 2) and be randomized in a 1:1 ratio to receive either Acthar Gel or matching placebo for an additional 12 weeks. A single participant might be involved in the trial for as many as 32 weeks.

Official Title
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A Multicenter, 2 Part Study to Assess the Efficacy and Safety of Acthar Gel in Subjects With Rheumatoid Arthritis With Persistently Active Disease Despite Dual-DMARD Treatment

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: Acthar Gel
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or nonpregnant, nonlactating female subjects Meets criteria for definite rheumatoid arthritis as defined by 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification at screening Has active disease defined as a score of >3.2 on DAS28-ESR prior to study drug administration despite dual-DMARD treatment Is on a stable dose of ≤ 20 mg per week of methotrexate for at least 8 weeks AND a stable dose of an allowed DMARD for at least 24 weeks prior to the screening visit May also be on a stable dose of 10 mg or less of prednisone or other the dose equivalent of another corticosteroid for 4 weeks prior to study drug administration Exclusion Criteria: Has current rheumatoid disease or inflammatory joint disease other than RA Has any history of use of adrenocorticotropic hormone (ACTH) for the treatment of RA Has taken B-cell mediated therapies in the 6 months prior to screening Has hepatitis B, hepatitis C, history of tuberculosis (TB) or other contraindication as per the United States (US) Prescribing Information for Acthar Has history of Type 1 or Type 2 diabetes Has any clinically significant infection

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Part 1: Single Group; Part 2: Parallel
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: All Enrolled Participants<br>All participants receive Acthar Gel 1 mL twice weekly for 12 weeks | Drug: Acthar Gel<br>* 80 Units Acthar Gel per 1 mL for subcutaneous injection<br>* Other names: H.P. Acthar Gel;|
| Experimental: Part 2: Acthar Gel<br>Participants receive Acthar Gel 1 mL twice weekly for an additional 12 weeks | Drug: Acthar Gel<br>* 80 Units Acthar Gel per 1 mL for subcutaneous injection<br>* Other names: H.P. Acthar Gel;|
| Placebo Comparator: Part 2: Placebo<br>Participants receive Placebo 1 mL twice weekly for an additional 12 weeks | Drug: Placebo<br>* Matching placebo 1 mL for subcutaneous injection<br>* Other names: Matching Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of Participants With Low Disease Activity (LDA) by Visit | LDA is defined as DAS28 <3.2. | Baseline to Week 12 | 
| Part 2: Number of Participants Who Maintained Low Disease Activity by Visit | Low disease activity is defined as DAS28 <3.2. | Week 12 to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Swollen Joint Count by Visit | The investigator counts the number of swollen joints used to calculate the Disease Activity Score (DAS28-ESR, DAS28) The DAS28 is a composite score derived from the following assessments: Swollen Joint Count Tender Joint Count Patient's Global Health Erythrocyte Sedimentation Rate | Baseline to Week 12 | 
| Part 2: Swollen Joint Count by Visit During Part 2 | The investigator counts the number of swollen joints used to calculate the Disease Activity Score (DAS28-ESR/DAS28) The DAS28 is a composite score derived from the following assessments: Swollen Joint Count Tender Joint Count Patient's Global Health Erythrocyte Sedimentation Rate | Baseline, Week 12 to Week 24 | 
| Part 1: Tender Joint Count by Visit | The investigator counts the number of tender joints used to calculate the Disease Activity Score (DAS28-ESR, DAS28) The DAS28 is a composite score derived from the following assessments: Swollen Joint Count Tender Joint Count Patient's Global Health Erythrocyte Sedimentation Rate | Baseline to Week 12 | 
| Part 2: Tender Joint Count by Visit | The investigator counts the number of tender joints used to calculate the Disease Activity Score (DAS28-ESR, DAS28) The DAS28 is a composite score derived from the following assessments: Swollen Joint Count Tender Joint Count Patient's Global Health Erythrocyte Sedimentation Rate | Baseline, Week 12 to Week 24 | 
| Part 1: Patient-Reported General Health by Visit | Participants rate their general health on a 100 mm visual analogue scale (VAS), where 0=best general health and 100=worst general health. A lower score indicates better general health. | Baseline to Week 12 | 
| Part 2: Patient-Reported General Health by Visit | Participants rate their general health on a 100 mm visual analogue scale (VAS), where 0=best general health and 100=worst general health. A lower score indicates better general health. | Baseline, Week 12 to Week 24 | 
| Part 1: Erythrocyte Sedimentation Rate (ESR) by Visit | The ESR is the rate at which red blood cells (in whole blood that has not clotted) fall to the bottom of the tube over a period of one hour. The clear liquid above the red blood cells is measured in millimeters after one hour (mm/hr). The normal range for ESR results is 1-13 mm/hr for males and 1/20 mm/hr for females. The ESR is a common test for inflammation and used to derive the DAS28. The DAS28 is a composite score derived from the following assessments: Swollen Joint Count Tender Joint Count Patient's Global Health Erythrocyte Sedimentation Rate | Baseline to Week 12 | 
| Part 2: Erythrocyte Sedimentation Rate (ESR) by Visit | The ESR is the rate at which red blood cells (in whole blood that has not clotted) fall to the bottom of the tube over a period of one hour. The clear liquid above the red blood cells is measured in millimeters after one hour (mm/hr). The normal range for ESR results is 1-13 mm/hr for males and 1/20 mm/hr for females. The ESR is a common test for inflammation and used to derive the DAS28. The DAS28 is a composite score derived from the following assessments: Swollen Joint Count Tender Joint Count Patient's Global Health Erythrocyte Sedimentation Rate | Baseline, Week 12 to Week 24 | 
| Part 1: Patient's Global Assessment of Pain by Visit | Patients rate their pain on a 100 mm VAS, where 0=no pain and 100=pain as bad as it could be. Higher scores indicate more pain. | Baseline to Week 12 | 
| Part 2: Patient's Global Assessment of Pain by Visit | Patients rate their pain on a 100 mm VAS, where 0=no pain and 100=pain as bad as it could be. Higher scores indicate more pain. | Baseline, Week 12 to Week 24 | 
| Part 1: Physician's Global Assessment of Disease Activities by Visit | The physician rates the participant's disease activity on a 100 mm visual analogue scale, where 0=very good and 100=very bad. Lower scores indicate improvement. | Baseline to Week 12 | 
| Part 2: Physician's Global Assessment of Disease Activities by Visit | The physician rates the participant's disease activity on a 100 mm visual analogue scale, where 0=very good and 100=very bad. Lower scores indicate improvement. | Week 12 to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Persistent disease activity