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. Paweł Hrycaj
  • Warszawa, Poland, 03-291
    • Centrum Medyczne FutureMeds Targowek
• Spain
  • A Coruña, 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: 16 years to 73 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	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

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 14, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue 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