A Study to Evaluate the Nipocalimab and Certolizumab Combination Therapy in Participants With Active Rheumatoid Arthritis (DAISY)

A Phase 2a Multicenter, Randomized, Double Blind, Parallel, Proof of Concept Study Evaluating the Efficacy and Safety of Nipocalimab and Certolizumab Combination Therapy in Participants With Active Rheumatoid Arthritis Despite Prior Treatment With Advanced Therapies (bDMARD or tsDMARD)

The purpose of this study is to evaluate the efficacy of combination therapy with nipocalimab and certolizumab compared to certolizumab monotherapy.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1417
    • Centro Privado de Medicina Familiar
  • Buenos Aires, Argentina, C1425EOE
    • Sanatorio Agote
  • Buenos Aires, Argentina, C1426BOR
    • Hospital Central Militar Cirujano Mayor Dr Cosme Argerich
  • Buenos Aires, Argentina, C1023AAB
    • STAT Research S A
  • CABA, Argentina, C1128AAF
    • Mautalen Salud e Investigación
  • CABA, Argentina, C1406AGA
    • ARCIS Salud SRL Aprillus asistencia e investigacion
  • San Miguel de Tucumán, Argentina, T4000AXL
    • Centro de Investigaciones Medicas Tucuman
• Germany
  • Hamburg, Germany, 20095
    • Hamburger Rheuma Forschungszentrum II
  • Herne, Germany, 44649
    • Rheumazentrum Ruhrgebiet
  • Ratingen, Germany, 40878
    • Rheumazentrum Ratingen
• Hungary
  • Budapest, Hungary, H-1027
    • Budai Irgalmasrendi Kórház
  • Gyula, Hungary, 5700
    • Bekes Varmegyei Kozponti Korhaz Pandy Kalman Tagkorhaz
  • Hódmezővásárhely, Hungary, 6800
    • Porcika Klinika - Vasarhelyi Sarkanyfu Kft.
  • Székesfehérvár, Hungary, 8000
    • CMed Rehabilitacios es Diagnosztikai Kozpont
  • Veszprém, Hungary, 8200
    • Vital Medical Center Orvosi es Fogaszati Kozpont
• Poland
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki Nr 2 Im Dr Jana Biziela W Bydgoszczy
  • Nadarzyn, Poland, 05 830
    • NZOZ Lecznica MAK MED S C
  • Warsaw, Poland, 02 665
    • Centrum Medyczne Reuma Park
  • Warsaw, Poland, 00 874
    • MICS Centrum Medyczne Warszawa
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital
  • Gillingham, United Kingdom, ME7 5NY
    • Medway NHS Foundation Trust
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Arizona Arthritis and Rheumatology Research PLLC
  • California
    • Huntington Beach, California, United States, 92648
      • Newport Huntington Medical Group
    • Upland, California, United States, 91786
      • Inland Rheumatology Clinical Trials Inc.
  • Florida
    • Brandon, Florida, United States, 33511
      • Bay Area Arthritis And Osteoporosis
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida
    • Plantation, Florida, United States, 33324
      • Integral Rheumatology and Immunology Specialists
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Atlanta Research Center for Rheumatology
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Graves Gilbert Clinic
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
  • Texas
    • Mesquite, Texas, United States, 75150
      • Southwest Rheumatology Research LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of rheumatoid arthritis (RA) and meeting the 2010 American college of rheumatology (ACR) or 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 of 66 swollen joints and 6 of 68 tender joints at the time of screening and at baseline
• Is positive for anti-citrullinated protein antibodies (ACPA) or rheumatoid factor (RF) by the central laboratory at the time of screening
• Has C-reactive protein (CRP) greater than or equal to (>=) 0.3 milligram per deciliter (mg/dL) by the central laboratory at the time of screening

• If has received prior biological disease-modifying antirheumatic drugs (bDMARDs) (or biosimilars) other than anti-tumor necrosis factor (anti-TNF) agent in RA, has demonstrated inadequate response (IR) or intolerance to the therapy based on one of the following:

  1. IR to at least 1bDMARD (or the biosimilars) other than anti-TNF agents, as assessed by the treating physician, after at least 12 weeks of therapy including but not limited to abatacept, anakinra, tocilizumab, and sarilumab or at least 16 weeks of therapy with rituximab Documented IR may include inadequate improvement or loss in response after initial improvement in joint counts or other parameters of disease activity
  2. Intolerance to bDMARD (or biosimilars) other than anti-TNF agent, as assessed by the treating physician. Documented intolerance includes side effects and injection or infusion reactions

• If has received prior anti-TNF agent (including biosimilars), has demonstrated IR to >=1 anti-TNF agent (including biosimilars), as assessed by the treating physician:

  1. After at least 12 weeks dosage of etanercept, adalimumab, golimumab (including biosimilars), and/or
  2. After at least 14 weeks dosage (example, at least 4 doses) of infliximab (including biosimilars) Documented IR may include inadequate improvement or loss in response after initial improvement in joint counts or other parameters of disease activity

Exclusion Criteria:

• Has a confirmed or suspected clinical immunodeficiency syndrome not related to treatment of RA or has a family history of congenital or hereditary immunodeficiency unless confirmed absent
• Is (anatomically or functionally) asplenic
• Has experienced myocardial infarction, unstable ischemic heart disease, or stroke less than or equal to (<=) 12 weeks of screening
• Has a diagnosis of congestive heart failure including medically controlled, asymptomatic congestive heart failure
• Has a history of known demyelinating disease such as multiple sclerosis or optic neuritis

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
Active Comparator: Certolizumab + Placebo; Participants will receive placebo intravenously (IV) and certolizumab dose 1 subcutaneously at Week 0, 2, and 4 followed by placebo IV and certolizumab dose 2 subcutaneously at Weeks 6 to 22.	Drug: Placebo; Placebo will be administered intravenously.; Drug: Certolizumab; Certolizumab will be administered subcutaneously.; Other Names: Cimzia
Experimental: Certolizumab + Nipocalimab; Participants will receive nipocalimab IV and certolizumab dose 1 subcutaneously at Week 0, 2, and 4 followed by nipocalimab IV and certolizumab dose 2 subcutaneously at Weeks 6 to 22.	Drug: Nipocalimab; Nipocalimab will be administered intravenously.; Other Names: JNJ-80202135; M281; Drug: Certolizumab; Certolizumab will be administered subcutaneously.; Other Names: Cimzia

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) Response 20 at Week 12	ACR20 response is defined as: greater than or equal to (>=)20 percent (%) 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 (arthritis, 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 Response 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 tender joint count (68 joints) and swollen joint count (66 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 Response at Week 12	Percentage of participants who achieved ACR70 response 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 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 (arthritis, VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis), patient's assessment of physical function as measured by (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 Response at Week 12	Percentage of participants who achieved ACR90 response 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 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 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	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 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.	Week 12
Percentage of Participants Who Achieved Disease Activity Index Score 28 Using C-reactive Protein (DAS28-CRP) Low Disease Activity (LDA) at Week 12	Percentage of participants who achieved DAS28-CRP LDA at Week 12 were reported. DAS28 LDA is defined as a DAS28 value of less than or equal to (<=3.2) at a visit. 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 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.	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, score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability.	Baseline (Week 0), Week 12
Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12	Change from baseline in CDAI at Week 12 were reported. The CDAI score is a derived score combining 4 disease assessments: tender joint counts (28 joints), swollen joint counts (28 joints), Patient's Global Assessment of Disease Activity (PtGA), and Physician's Global Assessment of Disease Activity (PGA). Change from baseline in CDAI score measured the change in disease activity, where a negative change indicated an improvement, and a positive change indicated a worsening. The total score range is 0-76. Score interpretation: Remission <=2.8; Low Disease Activity CDAI > 2.8 and <=10; Moderate Disease Activity CDAI >10 and <=22; High Disease Activity CDAI > 22.	Baseline (Week 0), Week 12

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): August 15, 2023
• Primary Completion (Actual): August 29, 2024
• Study Completion (Actual): October 29, 2024

Study Registration Dates

• First Submitted: September 1, 2023
• First Submitted That Met QC Criteria: September 1, 2023
• First Posted (Actual): September 8, 2023

Study Record Updates

• Last Update Posted (Estimated): October 16, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Arthritis, Rheumatoid; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Polymers; Macromolecular Substances; Immunoglobulin Fragments; Peptide Fragments; Polyethylene Glycols; Immunoglobulin Fab Fragments; Certolizumab Pegol
• Other Study ID Numbers: CR109343; 2023-504045-31-00 (Registry Identifier: EUCT number); 80202135ARA2002 (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 and 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