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

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy of combination therapy with nipocalimab and certolizumab compared to certolizumab monotherapy.

Official Title
-----------------
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)

Conditions
-----------------
Arthritis, Rheumatoid

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: Nipocalimab
* Drug: Certolizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
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: 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 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: After at least 12 weeks dosage of etanercept, adalimumab, golimumab (including biosimilars), and/or 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Certolizumab + Placebo<br>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<br>* Placebo will be administered intravenously.<br>Drug: Certolizumab<br>* Certolizumab will be administered subcutaneously.<br>* Other names: Cimzia;|
| Experimental: Certolizumab + Nipocalimab<br>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<br>* Nipocalimab will be administered intravenously.<br>* Other names: M281;Drug: Certolizumab<br>* Certolizumab will be administered subcutaneously.<br>* 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 score at Week 12 will be reported. DAS28-CRP is combined 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), CRP, and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP)1, MCP2, MCP3, MCP4, MCP5, proximal interphalangeal (PIP)1, PIP2, PIP3, PIP4, 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. Lower scores indicate better disease control and higher scores indicate worse disease control. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Response at Week 12 | Percentage of participants achieving ACR 20 response at Week 12 will be reported. ACR 20 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 global assessment of disease activity (arthritis, visual analog scale [VAS]; 0-100 mm, 0=excellent and 100=poor), patient's assessment of pain by VAS (VAS; 0-100 millimeter [mm], 0=no pain and 100=worst possible pain), patient's assessment of physical function measured by health assessment questionnaire-disability index (HAQ-DI), defined as a 20-question instrument assessing 8 functional areas, range: 0-3, 0=no difficulty, 3=inability to perform a task in that area, physician's global assessment of disease activity (VAS; 0-100 mm, 0=no arthritis activity, and 100=extremely active arthritis), and CRP. | At Week 12 | 
| Percentage of Participants Achieving ACR 50 Response at Week 12 | Percentage of participants achieving ACR 50 response at Week 12 will be reported. ACR 50 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 global assessment of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor), patient's assessment of pain by visual analog scale (VAS; 0-100 mm, 0=no pain and 100=worst possible pain), patient's assessment of physical function measured by HAQ-DI, defined as a 20-question instrument assessing 8 functional areas, range: 0-3, 0=no difficulty, 3=inability to perform a task in that area, physician's global assessment of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis), and CRP. | At Week 12 | 
| Percentage of Participants Achieving ACR 70 Response at Week 12 | Percentage of participants achieving ACR 70 response at Week 12 will be 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 global assessment of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor), patient's assessment of pain by visual analog scale (VAS; 0-100 mm, 0=no pain and 100=worst possible pain), patient's assessment of physical function measured by HAQ-DI, defined as a 20-question instrument assessing 8 functional areas), range: 0-3, 0=no difficulty, 3=inability to perform a task in that area, physician's global assessment of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis), and CRP. | At Week 12 | 
| Percentage of Participants Achieving ACR90 Response at Week 12 | Percentage of participants achieving ACR 90 response at Week 12 will be reported. ACR 90 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 global assessment of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor), patient's assessment of pain by visual analog scale (VAS; 0-100 mm, 0=no pain and 100=worst possible pain), patient's assessment of physical function measured by HAQ-DI, defined as a 20-question instrument assessing 8 functional areas), range: 0-3, 0=no difficulty, 3=inability to perform a task in that area, physician's global assessment of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis), and CRP. | At Week 12 | 
| Percentage of Participants Achieving DAS28-CRP Remission at Week 12 | Percentage of participants achieving DAS28-CRP level for remission at Week 12 will be reported. DAS28-CRP remission is defined as DAS28-CRP value less than (<) 2.6 at the analysis visit. | At Week 12 | 
| Percentage of Participants Achieving DAS28-CRP Low Disease Activity (LDA) at Week 12 | Percentage of participants achieving DAS28-CRP level for LDA at Week 12 will be reported. DAS28 LDA is defined as a DAS28 value of less than or equal to (<=) 3.2 at the analysis visit. | At 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 will be reported. 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, Week 12 | 
| Change From Baseline in Clinical Disease Activity Index Score (CDAI) at Week 12 | Change from baseline in CDAI score to Week 12 will be reported. The CDAI score is a derived combined 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 (arthritis, VAS; 0-10 centimeter (cm), 0=excellent and 10= poor), and physician's global assessment of disease activity (VAS; 0-10 cm, 0=no arthritis activity and 10=extremely active arthritis). CDAI total score ranges from 0 to 76. | Baseline, Week 12 | 
| Number 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 or 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 Week 30 | 
| Number 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 (The participant was at risk of death at the time of the event. It does not refer to an event that hypothetically might have caused death if it was more severe), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is a suspected transmission of any infectious agent via a medicinal product, and is medically important. Treatment-emergent SAEs are defined as SAEs with onset or worsening on or after date of first dose of study treatment. | Up to Week 30 | 
| Number of Participants With TEAEs Leading to Discontinuation of Study Intervention | Number of participants with TEAEs leading to discontinuation of study intervention will be reported. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment. | Up to Week 30 | 
| Number of Participants With Adverse Events of Special interests (AESIs) | Number of participants with AESIs will be reported. TEAEs associated with the following situations are considered to be AESIs: Infections that are severe or require intravenous (IV) anti-infective or operative or invasive intervention, clinically significant opportunistic infection (for example, active TB, invasive fungal infections), hypoalbuminemia with albumin level <20 gram per liter (g/L), and any newly identified malignancies. An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. | Up to Week 30 |