Multiple Dose Study of UCB4940 as add-on to Certolizumab Pegol in Subjects With Rheumatoid Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, efficacy and body distribution of Bimekizumab (UCB4940) when added to Certolizumab Pegol treatment in patients with Rheumatoid Arthritis. Neither the patient nor the doctor will know the treatment group.

Official Title
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A Double-blind, Randomized, Placebo-controlled Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Multiple Doses of UCB4940 Administered as Add-on to Certolizumab Pegol Therapy in Subjects With Moderate-to-Severe Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: Bimekizumab
* Biological: Certolizumab Pegol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria To be eligible to participate in this study, all of the following criteria must be met: Subject is informed and given approved written Informed Consent Form (ICF). Subject is considered reliable and capable of adhering to the protocol. Subject must have a diagnosis of adult-onset moderate-to-severe RA of at least 6 months' duration as defined by ACR/EULAR 2010 classification criteria. Subject must have: ≥6 tender joints (out of 68) ≥6 swollen joints (out of 66) CRP≥10.0mg/L . Subject must have had inadequate response to at least 1 synthetic DMARD. Subject is at least 18 years and less than 70 years of age at Visit 1 (Screening). Female subjects must either be: postmenopausal permanently sterilized or, if of childbearing potential, must be willing to use at least 2 effective methods of contraception, Male subjects with partners of childbearing potential must be willing to use a condom when sexually active, during the study and for 5 months after last administration of study drug. Exclusion Criteria Subjects are not permitted to enroll in the study if any of the following criteria is met: Subject has previously participated in this study or has previously been assigned to treatment in a study of the investigational medicinal product (IMP) under investigation in this study (UCB4940 and/or CZP). Subject has a history or active systemic/respiratory infection due to fungal, parasitic, or mycotic pathogens. Subjects with known tuberculosis (TB) infection, at high risk of acquiring TB infection, or latent TB infection are excluded. Subject is at high risk of infection. Subject has an active infection or has had a serious infection within 12 weeks prior to the first dose of study drug at Week 0. Subject has renal or liver impairment. Subject has a current or past history of gastrointestinal ulceration. Subject has active neoplastic disease or history of neoplastic disease. Subject has a concomitant diagnosis of any other inflammatory condition. Subject has a secondary, non-inflammatory condition or a known diagnosis of fibromyalgia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: CZP / CZP + PBO / CZP<br>Certolizumab Pegol (400 mg at Weeks 0, 2, and 4 followed by 200 mg every two weeks) until Week 30 +Placebo from Week 8 to Week 18 | Biological: Certolizumab Pegol<br>* Pharmaceutical form: Prefilled syringes Concentration: 200 mg/ml Route of administration: Subcutaneous injection<br>Other: Placebo<br>* Pharmaceutical form: Solution for infusion Concentration: 0.9% saline Route of administration: Intravenous infusion<br>|
| Experimental: CZP / CZP + UCB4940 / CZP<br>Certolizumab Pegol (400 mg at Weeks 0, 2, and 4 followed by 200 mg every two weeks) until Week 30 + UCB4940 from Week 8 until Week 18 | Biological: Bimekizumab<br>* Pharmaceutical form: Solution for infusion Concentration: Vials at 80 mg/ml will be diluted with 0.9% sodium chloride to a final concentration to achieve the correct dose Route of administration: iv infustion<br>Biological: Certolizumab Pegol<br>* Pharmaceutical form: Prefilled syringes Concentration: 200 mg/ml Route of administration: Subcutaneous injection<br>|
| Other: CZP / CZP/ CZP<br>Certolizumab Pegol (400 mg at Weeks 0, 2, and 4 followed by 200 mg every two Weeks) until Week 30 | Biological: Certolizumab Pegol<br>* Pharmaceutical form: Prefilled syringes Concentration: 200 mg/ml Route of administration: Subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events | All adverse events (AEs) are recorded during the entire study period. | Screening (D-28) until final study visit (Week 44) | 
| Change from Baseline 2 in DAS28(CRP) | DAS28 (Disease Activity Score 28) is a measure of disease activity in Rheumatoid Arthritis (RA) and is a composite score derived from the number of swollen and tender joints (out of 28), the CRP value and the patient global assessment of disease activity. | Week 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent improvement in ACR (American College of Rheumatology) criteria (ACRn) based on Baseline 2 | ACRn is the percentage improvement from Baseline 2 in the number of tender joints, in the number of swollen joints, and in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). | Week 20 | 
| ACR20 response based on Baseline 2 | The assessments are based on a 20% or greater improvement from Baseline 2 in the number of tender joints, in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). | Week 20 | 
| ACR50 response based on Baseline 2 | The assessments are based on a 20% or greater improvement from Baseline 2 in the number of tender joints, in the number of swollen joints, and a 50% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). | Week 20 | 
| ACR70 response based on Baseline 2 | The assessments are based on a 20% or greater improvement from Baseline 2 in the number of tender joints, in the number of swollen joints, and a 70% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). | Week 20 | 
| DAS28(CRP) remission | DAS28(CRP) remission is defined as DAS28(CRP) < 2.6. DAS28 is a measure of disease activity in RA and is a composite score derived from the number of swollen and tender joints (out of 28) , the C-reactive protein value and the patient global assessment of disease activity. | Week 20 |