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

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

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).

Study Overview

• Status: Completed
• Conditions: Arthritis, Rheumatoid
• Intervention / Treatment: Other: Placebo; Drug: Nipocalimab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Expanded Access

Temporarily not available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Germany
  • Hamburg, Germany, 20095
    • Hamburger Rheuma Forschungszentrum II
  • Ratingen, Germany, 40878
    • Rheumazentrum Ratingen
• Poland
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki nr 2 im dr Jana Biziela w Bydgoszczy
  • Nadarzyn, Poland, 05-830
    • NZOZ Lecznica Mak-Med sc
  • Poznan, Poland, 61 397
    • Prywatna Praktyka Lekarska Prof Um Dr Hab Med Pawel Hrycaj
  • Warszawa, Poland, 03 291
    • Centrum Medyczne AMED Targowek
• Spain
  • A Coruna, Spain, 15006
    • Hosp Univ A Coruna
  • Bilbao, Spain, 48013
    • Hosp. Univ. de Basurto
  • Santiago de Compostela, Spain, 15706
    • Hosp. Clinico Univ. de Santiago
  • Sevilla, Spain, 41009
    • Hosp. Virgen Macarena
  • Vigo, Spain, 36214
    • Hosp. Do Meixoeiro
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital NHS Trust
  • Newcastle, United Kingdom, NE29 8NH
    • North Tyneside General Hospital
  • Stoke on Trent, United Kingdom, ST6 7AG
    • Haywood Hospital
• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Arizona Arthritis & Rheumatology Associates PC
    • Mesa, Arizona, United States, 85210
      • Arizona Arthritis & Rheumatology Research, PLLC
    • Tucson, Arizona, United States, 85704
      • Arizona Arthritis & Rheumatology Research, PLLC
  • California
    • Palm Desert, California, United States, 92260
      • Desert Medical Advances
    • Poway, California, United States, 92064
      • Arthritis Care and Research Center Inc.: Smitha Reddy, MD
    • San Diego, California, United States, 92108
      • TriWest Research Associates, LLC
    • Upland, California, United States, 91786
      • Inland Rheumatology Clinical Trials, Inc.
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • DJL Clinical Research, PLLC
  • Ohio
    • Vandalia, Ohio, United States, 45377
      • STAT Research, Inc.
  • South Carolina
    • Summerville, South Carolina, United States, 29486
      • Low Country Rheumatology PA
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • West Tennessee Research Institute
  • Texas
    • Houston, Texas, United States, 77089
      • Accurate Clinical Research, Inc.
    • Mesquite, Texas, United States, 75150
      • Southwest Rheumatology Research LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group 1: Placebo; Participants will receive placebo intravenously (IV) every 2 weeks (q2w) through Week 10 along with standard-of-care background therapy.	Other: Placebo; Placebo infusion will be administered intravenously.
Experimental: Group 2: Nipocalimab; Participants will receive nipocalimab IV q2w through Week 10 along with standard-of-care background therapy.	Drug: Nipocalimab; Nipocalimab infusions will be administered intravenously.; Other Names: JNJ-80202135; M281

What is the study measuring?

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	Change from baseline in DAS28-CRP at Week 12 were reported. 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, and C-reactive protein (CRP; in milligrams per liter [mg/L]). The set of 28 joint count was based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. Score on the DAS28 ranged from 0 to 10, where higher scores indicated more disease activity. Negative changes from baseline indicated improvement of arthritis.	Baseline (Week 0), Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved American College of Rheumatology (ACR) 20 at Week 12	Percentage of participants who achieved ACR20 at Week 12 were reported. ACR20 response is defined as: greater than or equal to (>=)20% improvement 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 using visual analog scale (VAS; 0-100 millimeters [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 as measured by Disability Index of Health Assessment Questionnaire (HAQ-DI; 20-question instrument assessing 8 functional areas; range: 0-3, 0= no difficulty, 3= inability to perform task in that area), and CRP.	Week 12
Percentage of Participants Who Achieved American College of Rheumatology (ACR) 50 at Week 12	Percentage of participants who achieved ACR50 at Week 12 were reported. ACR50 response is defined as: >=50% improvement 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 using 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 as measured by Disability Index of Health Assessment Questionnaire (HAQ-DI; 20-question instrument assessing 8 functional areas; range: 0-3, 0= no difficulty, 3= inability to perform task in that area), and CRP.	Week 12
Percentage of Participants Who Achieved American College of Rheumatology (ACR) 70 at Week 12	Percentage of participants who achieved ACR70 at Week 12 were reported. ACR70 response is defined as: >=70% improvement 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 using 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 as measured by Disability Index of Health Assessment Questionnaire (HAQ-DI; 20-question instrument assessing 8 functional areas; range: 0-3, 0= no difficulty, 3= inability to perform task in that area), and CRP.	Week 12
Percentage of Participants Who Achieved American College of Rheumatology (ACR) 90 at Week 12	Percentage of participants who achieved ACR90 at Week 12 were reported. ACR90 response is defined as: >=90% improvement 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 using 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 as measured by Disability Index of Health Assessment Questionnaire (HAQ-DI; 20-question instrument assessing 8 functional areas; range: 0-3, 0= no difficulty, 3= inability to perform task in that area), and CRP.	Week 12
Percentage of Participants Who Achieved Disease Activity Index Score 28 Using C-reactive Protein (DAS28-CRP) Remission at Week 12	Percentage of participants who achieved DAS28-CRP remission at Week 12 were reported. The DAS28 remission is defined as DAS28 -CRP value of less than (<) 2.6 at Week 12. 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, and CRP; in mg/L). The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, MCP1 to MCP5, PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. Score on the DAS28 ranged from 0 to 10, where higher scores indicated more disease activity. Negative changes from baseline indicated improvement of arthritis.	Week 12
Percentage of Participants Who Achieved Disease Activity Index Score 28 Using C-reactive Protein (DAS28-CRP) Low Disease Activity (LDA) European League Against Rheumatism (EULAR) at Week 12	Percentage of participants who achieved DAS28-CRP LDA EULAR at Week 12 were reported. The DAS28 LDA EULAR is defined as DAS28 -CRP value of less than or equal to (<=) 3.2 at Week 12. 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, and C-reactive protein (CRP; in mg/L). The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, MCP1 to MCP5, PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. Score on the DAS28 ranged from 0 to 10, where higher scores indicated more disease activity. Negative changes from baseline indicated improvement of arthritis.	Week 12
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 12	Change from baseline in HAQ-DI score at Week 12 were reported. The HAQ-DI is a patient-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 activities of daily living, over the past week. Responses in each functional area were scored on a scale from 0 (indicating no difficulty) to 3 (inability to perform a task in that area). Overall score was computed as the sum of category scores and divided by the number of categories answered and ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability.	Baseline (Week 0), Week 12
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)	Percentage of participants with TEAEs were reported. An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs were defined as any AE occurring at or after the initial administration of study intervention through the safety follow-up visit (8 weeks after the last administration of study intervention).	From Week 0 up to 8 weeks post last dose at Week 10 (up to Week 18)
Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs)	Percentage of participants with TESAEs were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was any untoward medical occurrence at any dose that: resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/ incapacity, or resulted in congenital anomaly/birth defect. TESAEs were defined as any SAE occurring at or after the initial administration of study intervention through the safety follow-up visit (8 weeks after the last administration of study intervention).	From Week 0 up to 8 weeks post last dose at Week 10 (up to Week 18)
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention	Percentage of participants with AEs leading to discontinuation of study intervention were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention.	From Week 0 up to Week 10
Percentage of Participants With Treatment-emergent Adverse Events of Special Interest (AESIs)	Percentage of participants with TEAEs of special interest were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs were defined as any AE occurring at or after the initial administration of study intervention through the safety follow-up visit (8 weeks after the last administration of study intervention). TEAEs associated with the following situations were considered to be AESIs: (a) Infections that were severe or require IV anti-infective or operative/invasive intervention; (b) Hypoalbuminemia with albumin <20 grams per liter (g/L) (<2.0 grams per deciliter [g/dL]).	From Week 0 up to 8 weeks post last dose at Week 10 (up to Week 18)

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2021
• Primary Completion (Actual): August 10, 2022
• Study Completion (Actual): August 10, 2022

Study Registration Dates

• First Submitted: August 2, 2021
• First Submitted That Met QC Criteria: August 2, 2021
• First Posted (Actual): August 5, 2021

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 4, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: CR109058; 2021-000510-42 (EudraCT Number); 80202135ARA2001 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No