Clinical trial NCT04991753: A Proof-of-concept Study of the Efficacy and Safety of Nipocalimab in Participants With Active Rheumatoid Arthritis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Arthritis, Rheumatoid
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2021-08-05
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from Baseline in Disease Activity Index Score 28 Using C-reactive Protein (DAS28-CRP) at Week 12
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Percentage of Participants who Achieve American College of Rheumatology (ACR) 20 at Week 12
timeFrame: Week 12
measure: Percentage of Participants who Achieve ACR50 at Week 12
timeFrame: Week 12
measure: Percentage of Participants who Achieve ACR70 at Week 12
timeFrame: Week 12
measure: Percentage of Participants who Achieve ACR90 at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving DAS28-CRP Remission at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving DAS28-CRP Low Disease Activity (LDA) at Week 12
timeFrame: Week 12
measure: Change from Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 12
timeFrame: Baseline, up to Week 12
measure: Percentage of Participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 24 weeks
measure: Percentage of Participants with Treatment-emergent Serious Adverse Events (SAEs)
timeFrame: Up to 24 weeks
measure: Percentage of Participants with TEAEs Leading to Discontinuation of Study Intervention
timeFrame: Up to 24 weeks
measure: Percentage of Participants with Adverse Events of Special interests (AESIs)
timeFrame: Up to 24 weeks
measure: Percentage of Participants with Change from Baseline in Clinical Laboratory Abnormalities Over Time
timeFrame: Up to 24 weeks
measure: Percentage of Participants with Change from Baseline in Vital Signs Abnormalities Over Time
timeFrame: Up to 24 weeks
measure: Serum Concentration of Nipocalimab Over Time
timeFrame: Up to Week 18
measure: Percentage of Participants with Antibodies to Nipocalimab (Anti-drug Antibodies [ADAs] and Neutralizing Antibodies [NAbs])
timeFrame: Up to Week 18
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Arizona Arthritis & Rheumatology Associates PC
state: Arizona
city: Mesa
country: United States
facility: Arizona Arthritis & Rheumatology Research, PLLC
state: Arizona
city: Tucson
country: United States
facility: Arizona Arthritis & Rheumatology Research, PLLC
state: Arizona
city: Palm Desert
country: United States
facility: Desert Medical Advances
state: California
city: Poway
country: United States
facility: Arthritis Care and Research Center Inc.: Smitha Reddy, MD
state: California
city: San Diego
country: United States
facility: TriWest Research Associates, LLC
state: California
city: Upland
country: United States
facility: Inland Rheumatology Clinical Trials, Inc.
state: California
city: Charlotte
country: United States
facility: DJL Clinical Research, PLLC
state: North Carolina
city: Vandalia
country: United States
facility: STAT Research, Inc.
state: Ohio
city: Summerville
country: United States
facility: Low Country Rheumatology PA
state: South Carolina
city: Jackson
country: United States
facility: West Tennessee Research Institute
state: Tennessee
city: Houston
country: United States
facility: Accurate Clinical Research, Inc.
state: Texas
city: Mesquite
country: United States
facility: Southwest Rheumatology Research LLC
state: Texas
city: Hamburg
country: Germany
facility: Hamburger Rheuma Forschungszentrum II
city: Ratingen
country: Germany
facility: Rheumazentrum Ratingen
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im dr Jana Biziela w Bydgoszczy
city: Nadarzyn
country: Poland
facility: NZOZ Lecznica Mak-Med sc
city: Poznan
country: Poland
facility: Prywatna Praktyka Lekarska Prof Um Dr Hab Med Pawel Hrycaj
city: Warszawa
country: Poland
facility: Centrum Medyczne AMED Targowek
city: A Coruna
country: Spain
facility: Hosp Univ A Coruna
city: Bilbao
country: Spain
facility: Hosp. Univ. de Basurto
city: Santiago de Compostela
country: Spain
facility: Hosp. Clinico Univ. de Santiago
city: Sevilla
country: Spain
facility: Hosp. Virgen Macarena
city: Vigo
country: Spain
facility: Hosp. Do Meixoeiro
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: London
country: United Kingdom
facility: Kings College Hospital NHS Trust
city: Newcastle
country: United Kingdom
facility: North Tyneside General Hospital
city: Stoke on Trent
country: United Kingdom
facility: Haywood Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: