Study to Assess if ABP710 is Safe & Effective in Treating Moderate to Severe Rheumatoid Arthritis Compared to Infliximab

Study Overview
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Brief Summary
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The main purpose of the study was to compare rheumatoid arthritis symptom improvement in participants who were given ABP 710 to those who were given infliximab, 22 weeks after starting treatment.

Official Title
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A Randomized, Double-Blind Phase 3 Study to Assess the Efficacy and Safety of ABP 710 Compared to Infliximab in Subjects With Moderate to Severe Rheumatoid Arthritis

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Biological: ABP 710
* Biological: Infliximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject (man or woman) is ≥ 18 and ≤ 80 years old. Subject is diagnosed with rheumatoid arthritis (RA) as determined by meeting the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria for RA. Subject has RA duration of at least 3 months. Subject has active RA defined as ≥ 6 swollen joints and ≥ 6 tender joints (based on 66/68 joint count excluding distal interphalangeal joints) at screening and baseline and at least 1 of the following at screening: erythrocyte sedimentation rate ≥ 28 mm/hr serum C-reactive protein > 1.0 mg/dL Subject has a positive rheumatoid factor or anti-cyclic citrullinated peptide at screening. Subject has taken methotrexate (MTX) for ≥ 12 consecutive weeks and is on a stable dose of oral or subcutaneous MTX 7.5 to 25 mg/week for ≥ 8 weeks before receiving the investigational product and is willing to remain on a stable dose throughout the study. For a subject on nonsteroidal anti-inflammatory drugs (NSAIDs) or low potency analgesics such as tramadol, Soma Compounds, Fioricet, or Fiorinal, the dose should be stable for ≥ 2 weeks before screening. For a subject on oral corticosteroids (≤ 10 mg prednisone or equivalent), the dose should be stable for ≥ 4 weeks before screening. Subject has no known history of active tuberculosis. Subject has a negative test for tuberculosis during screening defined as either: negative purified protein derivative (PPD) defined as < 5 mm of induration at 48 to 72 hours after test is placed OR negative Quantiferon test Subject with a positive PPD and a history of Bacillus Calmette-Guérin vaccination is allowed with a negative Quantiferon test. Subject with a positive PPD test (without a history of Bacillus Calmette-Guérin vaccination) or a subject with a positive or indeterminate Quantiferon test is allowed if they have all of the following: no symptoms of tuberculosis according to the worksheet provided by the sponsor, Amgen Inc. documented history of adequate prophylaxis initiation before receiving investigational product in accordance with local recommendations no known exposure to a case of active tuberculosis after most recent prophylaxis Exclusion Criteria: Subject has a history of prosthetic or native joint infection. Subject has an active infection or history of infections as follows: any active infection for which systemic anti-infectives were used within 28 days before first dose of investigational product a serious infection, defined as requiring hospitalization or intravenous (IV) anti-infective(s) within 8 weeks before the first dose of investigational product recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject Subject has a positive blood test for human immunodeficiency virus (HIV). Subject has a positive hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C virus antibody result at screening. Subject has uncontrolled, clinically significant systemic disease such as diabetes mellitus, cardiovascular disease including moderate or severe heart failure (New York Heart Association Class III/IV), renal disease, liver disease, or hypertension. Subject had a malignancy within 5 years EXCEPT for treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal carcinoma. Subject has a history of neurologic symptoms suggestive of central or peripheral nervous system demyelinating disease. Subject has a major chronic inflammatory disease or connective tissue disease other than RA, with the exception of secondary Sjögren's syndrome. Subject has a concurrent medical condition that, in the opinion of the investigator, could cause this study to be detrimental to the subject. Subject has laboratory abnormalities at screening, including any of the following: hemoglobin < 9 g/dL platelet count < 100 000/mm³ white blood cell count < 3 000/mm³ aspartate aminotransferase and/or alanine aminotransferase ≥ 2.0 x the upper limit of normal creatinine clearance < 50 mL/min (Cockroft-Gault formula) any other laboratory abnormality, that, in the opinion of the investigator, will prevent the subject from completing the study or will interfere with the interpretation of the study results. Subject has used commercially available or investigational biologic therapies for RA as follows: anakinra, etanercept within 1 month before the first dose of investigational product abatacept, tocilizumab, adalimumab, golimumab, certolizumab within 3 months before the first dose of investigational product other experimental or commercially available biologic therapies for RA within 3 months or 5 half-lives (whichever is longer) before the first dose of investigational product rituximab within 9 months before the investigational product along with evidence of incomplete B cell recovery Subject has received live vaccines within 28 days before the first dose of investigational product or plans to receive live vaccines during the course of the study. Subject has previously received Remicade® (infliximab) or a biosimilar of infliximab. Woman who is pregnant or breast feeding, or plans to become pregnant while enrolled in the study and for 6 months after the last dose of investigational product. Women of childbearing potential (ie, neither surgically sterile nor postmenopausal) and do not agree to use adequate contraception (eg, true abstinence, sterilization, birth control pills, Depo-Provera® [medroxyprogesterone] injections, or contraceptive implants) while on study and for 6 months after the last dose of investigational product.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABP 710<br>Participants randomized to receive a 3 mg/kg intravenous (IV) infusion of ABP 710 on day 1, at weeks 2 and 6, and every 8 weeks thereafter until week 22. At week 22 participants continued receiving 3 mg/kg ABP 710 every 8 weeks through week 46. | Biological: ABP 710<br>* Administered by intravenous infusion<br>|
| Active Comparator: Infliximab<br>Participants randomized to receive a 3 mg/kg IV infusion of infliximab on day 1, at weeks 2 and 6, and every 8 weeks thereafter until week 22. At week 22 participants were re-randomized in a 1:1 ratio to either continue receiving 3 mg/kg infliximab every 8 weeks or transition to receive 3 mg/kg ABP 710 every 8 weeks through week 46. | Biological: Infliximab<br>* Administered by intravenous infusion<br>* Other names: Remicade®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 22 | The primary efficacy endpoint was the response difference (RD) of 20% improvement in ACR core set measurements (ACR20) at week 22. A positive ACR20 response is defined if the following 3 criteria for improvement from baseline were met: ≥ 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: Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale [VAS]); Patient's global health assessment (measured on a 100 mm VAS); Investigator's global health assessment (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-reactive protein concentration. | Baseline and week 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an ACR20 Response Through Week 14 | A positive ACR20 response is defined if the following 3 criteria for improvement from baseline were met: ≥ 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: Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale [VAS]); Patient's global health assessment (measured on a 100 mm VAS); Investigator's global health assessment (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-reactive protein concentration. | Baseline and weeks 2, 6, and 14 | 
| Percentage of Participants With an ACR20 Response After Week 22 | A positive ACR20 response is defined if the following 3 criteria for improvement from baseline were met: ≥ 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: Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale [VAS]); Patient's global health assessment (measured on a 100 mm VAS); Investigator's global health assessment (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-reactive protein concentration. | Baseline and weeks 30, 34, 38, 46, and 50 | 
| Percentage of Participants With an ACR50 Response Through Week 22 | A positive ACR50 response is defined if the following 3 criteria for improvement from baseline were met: ≥ 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: Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale [VAS]); Patient's global health assessment (measured on a 100 mm VAS); Investigator's global health assessment (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-reactive protein concentration. | Baseline and weeks 2, 6, 14, and 22 | 
| Percentage of Participants With an ACR50 Response After Week 22 | A positive ACR50 response is defined if the following 3 criteria for improvement from baseline were met: ≥ 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: Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale [VAS]); Patient's global health assessment (measured on a 100 mm VAS); Investigator's global health assessment (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-reactive protein concentration. | Baseline and weeks 30, 34, 38, 46, and 50 | 
| Percentage of Participants With an ACR70 Response Through Week 22 | A positive ACR70 response is defined if the following 3 criteria for improvement from baseline were met: ≥ 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: Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale [VAS]); Patient's global health assessment (measured on a 100 mm VAS); Investigator's global health assessment (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-reactive protein concentration. | Baseline and weeks 2, 6, 14, and 22 | 
| Percentage of Participants With an ACR70 Response After Week 22 | A positive ACR70 response is defined if the following 3 criteria for improvement from baseline were met: ≥ 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: Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale [VAS]); Patient's global health assessment (measured on a 100 mm VAS); Investigator's global health assessment (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-reactive protein concentration. | Baseline and weeks 30, 34, 38, 46, and 50 | 
| Change From Baseline in Disease Activity Score 28 (DAS28) Through Week 22 | The DAS28 measures the severity of disease at a specific time and is derived from the following variables: 28 tender joint count 28 swollen joint count C-reactive protein (CRP) Patient's global health assessment measured on a 100 mm VAS, where 0 mm = no RA activity and 100 mm = worst RA activity imaginable. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. | Baseline and weeks 2, 6, 14, and 22 | 
| Change From Baseline in Disease Activity Score 28 (DAS28) After Week 22 | The DAS28 measures the severity of disease at a specific time and is derived from the following variables: 28 tender joint count 28 swollen joint count C-reactive protein (CRP) Patient's global health assessment measured on a 100 mm VAS, where 0 mm = no RA activity and 100 mm = worst RA activity imaginable. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. | Baseline and weeks 30, 34, 38, 46, and 50 |