A Proof-of-concept Study of the Efficacy and Safety of Nipocalimab in Participants With Active Rheumatoid Arthritis
- Registration Number
- NCT04991753
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 53
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1: Placebo Placebo Participants will receive placebo intravenously (IV) every 2 weeks (q2w) through Week 10 along with standard-of-care background therapy. Group 2: Nipocalimab Nipocalimab Participants will receive nipocalimab IV q2w through Week 10 along with standard-of-care background therapy.
- Primary Outcome Measures
Name Time Method Change from Baseline in Disease Activity Index Score 28 Using C-reactive Protein (DAS28-CRP) at Week 12 Baseline to 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving DAS28-CRP Low Disease Activity (LDA) at Week 12 Week 12 DAS28 LDA is defined as a DAS28 value of \>=2.6 and \<=3.2 at the analysis visit.
Percentage of Participants who Achieve ACR90 at Week 12 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.
Percentage of Participants Achieving DAS28-CRP Remission at Week 12 Week 12 DAS28-CRP remission is defined as DAS28-CRP value less than (\<) 2.6 at the analysis visit.
Change from Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 12 Baseline, up to 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.
Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) Up to 24 weeks 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.
Percentage of Participants with Treatment-emergent Serious Adverse Events (SAEs) Up to 24 weeks 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.
Percentage of Participants with TEAEs Leading to Discontinuation of Study Intervention Up to 24 weeks Percentage of participants with TEAEs leading to discontinuation of study intervention will be reported.
Percentage of Participants with Adverse Events of Special interests (AESIs) Up to 24 weeks Percentage of participants with AESIs will be reported.
Percentage of Participants with Change from Baseline in Clinical Laboratory Abnormalities Over Time Up to 24 weeks Percentage of participants with change from baseline in clinical laboratory abnormalities over time will be reported.
Percentage of Participants with Change from Baseline in Vital Signs Abnormalities Over Time Up to 24 weeks 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.
Serum Concentration of Nipocalimab Over Time Up to Week 18 Serum concentration of nipocalimab over time in participants receiving active study intervention will be reported.
Percentage of Participants with Antibodies to Nipocalimab (Anti-drug Antibodies [ADAs] and Neutralizing Antibodies [NAbs]) Up to Week 18 Percentage of participants with antibodies to nipocalimab (ADAs and NAbs) in participants receiving active study intervention will be reported.
Percentage of Participants who Achieve American College of Rheumatology (ACR) 20 at Week 12 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.
Percentage of Participants who Achieve ACR50 at Week 12 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.
Percentage of Participants who Achieve ACR70 at Week 12 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.
Trial Locations
- Locations (27)
Prywatna Praktyka Lekarska Prof Um Dr Hab Med Pawel Hrycaj
🇵🇱Poznan, Poland
Arizona Arthritis & Rheumatology Associates PC
🇺🇸Glendale, Arizona, United States
Arizona Arthritis & Rheumatology Research, PLLC
🇺🇸Tucson, Arizona, United States
Desert Medical Advances
🇺🇸Palm Desert, California, United States
Arthritis Care and Research Center Inc.: Smitha Reddy, MD
🇺🇸Poway, California, United States
TriWest Research Associates, LLC
🇺🇸San Diego, California, United States
Inland Rheumatology Clinical Trials, Inc.
🇺🇸Upland, California, United States
DJL Clinical Research, PLLC
🇺🇸Charlotte, North Carolina, United States
STAT Research, Inc.
🇺🇸Vandalia, Ohio, United States
Low Country Rheumatology PA
🇺🇸Summerville, South Carolina, United States
West Tennessee Research Institute
🇺🇸Jackson, Tennessee, United States
Accurate Clinical Research, Inc.
🇺🇸Houston, Texas, United States
Southwest Rheumatology Research LLC
🇺🇸Mesquite, Texas, United States
Hamburger Rheuma Forschungszentrum II
🇩🇪Hamburg, Germany
Rheumazentrum Ratingen
🇩🇪Ratingen, Germany
Szpital Uniwersytecki nr 2 im dr Jana Biziela w Bydgoszczy
🇵🇱Bydgoszcz, Poland
NZOZ Lecznica Mak-Med sc
🇵🇱Nadarzyn, Poland
Centrum Medyczne AMED Targowek
🇵🇱Warszawa, Poland
Hosp Univ A Coruna
🇪🇸A Coruna, Spain
Hosp. Univ. de Basurto
🇪🇸Bilbao, Spain
Hosp. Clinico Univ. de Santiago
🇪🇸Santiago de Compostela, Spain
Hosp. Virgen Macarena
🇪🇸Sevilla, Spain
Hosp. Do Meixoeiro
🇪🇸Vigo, Spain
Western General Hospital
🇬🇧Edinburgh, United Kingdom
Kings College Hospital NHS Trust
🇬🇧London, United Kingdom
North Tyneside General Hospital
🇬🇧Newcastle, United Kingdom
Haywood Hospital
🇬🇧Stoke on Trent, United Kingdom