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 (Week 0), 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Who Achieved American College of Rheumatology (ACR) 20 at Week 12 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.
Percentage of Participants Who Achieved American College of Rheumatology (ACR) 50 at Week 12 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.
Percentage of Participants Who Achieved American College of Rheumatology (ACR) 70 at Week 12 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.
Percentage of Participants Who Achieved American College of Rheumatology (ACR) 90 at Week 12 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.
Percentage of Participants Who Achieved Disease Activity Index Score 28 Using C-reactive Protein (DAS28-CRP) Remission at Week 12 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.
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 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.
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 12 Baseline (Week 0), 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.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) From Week 0 up to 8 weeks post last dose at Week 10 (up to Week 18) 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).
Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs) From Week 0 up to 8 weeks post last dose at Week 10 (up to Week 18) 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).
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 0 up to Week 10 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.
Percentage of Participants With Treatment-emergent Adverse Events of Special Interest (AESIs) From Week 0 up to 8 weeks post last dose at Week 10 (up to Week 18) 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 \[g/dL\]).
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
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