A Proof-of-concept Study of the Efficacy and Safety of Nipocalimab in Participants With Active Rheumatoid Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of nipocalimab versus placebo in participants with moderate to severe active rheumatoid arthritis (RA).

Detailed Description
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RA is a chronic autoimmune inflammatory disorder of unknown etiology that occurs in approximately 1 percent (%) of the population. Nipocalimab (also referred to as JNJ-80202135 and M281) is a fully human aglycosylated immunoglobulin (Ig)G1 monoclonal antibody designed to selectively bind, saturate, and block the IgG binding site on the endogenous neonatal fragment crystallizable (Fc) receptor (FcRn). Nipocalimab has a unique mechanism of action whereby it blocks the IgG binding site on endogenous FcRn and is expected to decrease pathogenic IgG antibody concentrations. A significant involvement of pathogenic IgG antibodies has been demonstrated in autoimmune diseases including RA. The primary hypothesis is that treatment with nipocalimab intravenously (IV) every 2 weeks (q2w) is superior to placebo in participants with moderate to severe active rheumatoid arthritis (RA) as assessed by the mean change from baseline in the disease activity index score 28 using C-reactive Protein (DAS28-CRP) at Week 12. The study consists of a Screening Period (less than or equal to [<=] 6 Weeks), Double-blind Treatment Period (12 Weeks), and a Safety Follow-up Period (6 Weeks). Key safety assessments will include adverse events (AEs), serious adverse events (SAEs), adverse events of special interests (AESIs), clinical laboratory safety tests (hematology, chemistry, and lipid profile), vital signs, and physical examination. The total duration of the study is up to 24 weeks.

Official Title
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A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, Proof-of-concept Study Evaluating the Efficacy and Safety of Nipocalimab Administered Intravenously in Participants With Active Rheumatoid Arthritis Despite Standard Therapy

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Other: Placebo
* Drug: Nipocalimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of rheumatoid arthritis (RA) and meeting the 2010 American college of rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria for RA for at least 3 months before screening Has moderate to severe active RA as defined by persistent disease activity with at least 6 swollen and 6 tender joints out of the 66/68-swollen and tender joint count at the time of screening and at baseline Is positive for anti-citrullinated protein antibodies (ACPA) and/or rheumatoid factor (RF) at screening Screening C-reactive protein (CRP) greater than or equal to (>=) 0.3 milligram per deciliter (mg/dL) by the central laboratory A woman of childbearing potential must have a negative highly sensitive urine pregnancy test (beta-human chorionic gonadotropin [beta-hCG]) at screening and a negative urine (beta-hCG) pregnancy test at Week 0 prior to administration of study intervention Exclusion Criteria: Has any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her RA or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant Currently has a malignancy or has a history of malignancy within 3 years before screening (with the exception of localized basal cell carcinoma and/or squamous cell carcinoma skin cancer that has been adequately treated with no evidence of recurrence for at least 12 weeks before the first administration of study intervention or cervical carcinoma in situ that has been treated with no evidence of recurrence for at least 3 months before the first administration of study intervention) Is (anatomically or functionally) asplenic Has experienced myocardial infarction (MI), unstable ischemic heart disease, or stroke within 12 weeks of screening Has other known inflammatory diseases that might confound the evaluations of benefit from nipocalimab therapy, including but not limited to ankylosing spondylitis, psoriatic arthritis, systemic lupus erythematosus, Lyme disease Is currently taking immunoglobulin (Ig)G fragment crystallizable (Fc)-related protein therapeutics

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group 1: Placebo<br>Participants will receive placebo intravenously (IV) every 2 weeks (q2w) through Week 10 along with standard-of-care background therapy. | Other: Placebo<br>* Placebo infusion will be administered intravenously.<br>|
| Experimental: Group 2: Nipocalimab<br>Participants will receive nipocalimab IV q2w through Week 10 along with standard-of-care background therapy. | Drug: Nipocalimab<br>* Nipocalimab infusions will be administered intravenously.<br>* Other names: M281;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Disease Activity Index Score 28 Using C-reactive Protein (DAS28-CRP) at Week 12 | DAS28-CRP is a composite index used to assess rheumatoid arthritis (RA) 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, and CRP. Change from baseline in DAS28-CRP measures the change in disease activity, where a negative change indicates an improvement, and a positive change indicates a worsening. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants who Achieve American College of Rheumatology (ACR) 20 at Week 12 | ACR20 response is defined greater than or equal to (>=) 20 percent (%) from baseline in both swollen joint count (66 joints) and tender joint count (68 joints), and >=20% improvement from baseline in 3 of 5 assessments: patient's assessment of pain by visual analog scale (VAS; 0-100 millimeter [mm], 0=no pain and 100=worst possible pain), patient's global assessment of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor), physician's global assessment of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis), patient's assessment of physical function measured by health assessment questionnaire-disability index (HAQ-DI, a 20-question instrument assessing 8 functional areas), range: 0-3, 0=no difficulty, 3=inability to perform a task in that area), and CRP. | Week 12 | 
| Percentage of Participants who Achieve ACR50 at Week 12 | ACR50 response is defined >=50% from baseline in both swollen joint count (66 joints) and tender joint count (68 joints), and >=50% improvement from baseline in 3 of 5 assessments: patient's assessment of pain by VAS (0-100 mm, 0=no pain and 100=worst possible pain), patient's global assessment of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor), physician's global assessment of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis), patient's assessment of physical function measured by HAQ-DI (a 20-question instrument assessing 8 functional areas, range: 0-3, 0=no difficulty, 3=inability to perform a task in that area), and CRP. | Week 12 | 
| Percentage of Participants who Achieve ACR70 at Week 12 | ACR70 response is defined >=70% from baseline in both swollen joint count (66 joints) and tender joint count (68 joints), and >=70% improvement from baseline in 3 of 5 assessments: patient's assessment of pain by visual analog scale (VAS; 0-100 mm, 0=no pain and 100=worst possible pain), patient's global assessment of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor), physician's global assessment of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis), patient's assessment of physical function measured by HAQ-DI (a 20-question instrument assessing 8 functional areas, range: 0-3, 0=no difficulty, 3=inability to perform a task in that area), and CRP. | Week 12 | 
| Percentage of Participants who Achieve ACR90 at Week 12 | ACR90 response is defined >=90% from baseline in both swollen joint count (66 joints) and tender joint count (68 joints), and >=90% improvement from baseline in 3 of 5 assessments: patient's assessment of pain by visual analog scale (VAS; 0-100 mm, 0=no pain and 100=worst possible pain), patient's global assessment of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor), physician's global assessment of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis), patient's assessment of physical function measured by HAQ-DI (a 20-question instrument assessing 8 functional areas, range: 0-3, 0=no difficulty, 3=inability to perform a task in that area), and CRP. | Week 12 | 
| Percentage of Participants Achieving DAS28-CRP Remission at Week 12 | DAS28-CRP remission is defined as DAS28-CRP value less than (<) 2.6 at the analysis visit. | Week 12 | 
| Percentage of Participants Achieving DAS28-CRP Low Disease Activity (LDA) at Week 12 | DAS28 LDA is defined as a DAS28 value of >=2.6 and <=3.2 at the analysis visit. | Week 12 | 
| Change from Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 12 | The functional status of the participant will be assessed using the HAQ-DI. This 20 question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. Lower scores are indicative of better functioning. | Baseline, up to Week 12 | 
| Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment. | Up to 24 weeks | 
| Percentage of Participants with Treatment-emergent Serious Adverse Events (SAEs) | SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. Treatment-emergent SAEs are defined as SAEs with onset or worsening on or after date of first dose of study treatment. | Up to 24 weeks | 
| Percentage of Participants with TEAEs Leading to Discontinuation of Study Intervention | Percentage of participants with TEAEs leading to discontinuation of study intervention will be reported. | Up to 24 weeks | 
| Percentage of Participants with Adverse Events of Special interests (AESIs) | Percentage of participants with AESIs will be reported. | Up to 24 weeks | 
| Percentage of Participants with Change from Baseline in Clinical Laboratory Abnormalities Over Time | Percentage of participants with change from baseline in clinical laboratory abnormalities over time will be reported. | Up to 24 weeks | 
| Percentage of Participants with Change from Baseline in Vital Signs Abnormalities Over Time | Percentage of participants with change from baseline in vital signs abnormalities (including temperature, pulse/heart rate, respiratory rate, and blood pressure) over time will be reported. | Up to 24 weeks | 
| Serum Concentration of Nipocalimab Over Time | Serum concentration of nipocalimab over time in participants receiving active study intervention will be reported. | Up to Week 18 | 
| Percentage of Participants with Antibodies to Nipocalimab (Anti-drug Antibodies [ADAs] and Neutralizing Antibodies [NAbs]) | Percentage of participants with antibodies to nipocalimab (ADAs and NAbs) in participants receiving active study intervention will be reported. | Up to Week 18 |