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

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

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Biological: Certolizumab Pegol; Other: Placebo; Biological: Bimekizumab

• Study Type: Interventional
• Enrollment (Actual): 159
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Praha 7, Czechia
    • Ra0123 101
• Hungary
  • Balatonfured, Hungary
    • Ra0123 203
  • Budapest, Hungary
    • Ra0123 201
  • Budapest, Hungary
    • Ra0123 202
  • Budapest, Hungary
    • Ra0123 204
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
    • Ra0123 801
• Poland
  • Bialystok, Poland
    • Ra0123 303
  • Lublin, Poland
    • Ra0123 306
  • Poznan, Poland
    • Ra0123 304
  • Poznan, Poland
    • Ra0123 305
  • Warszawa, Poland
    • Ra0123 301
• Russian Federation
  • Moscow, Russian Federation
    • Ra0123 403
  • Moscow, Russian Federation
    • Ra0123 404
  • Moscow, Russian Federation
    • Ra0123 405
  • Moscow, Russian Federation
    • Ra0123 406
  • Moscow, Russian Federation
    • Ra0123 408
  • Saint Petersburg, Russian Federation
    • Ra0123 407
  • Yaroslavl, Russian Federation
    • Ra0123 402
  • Yaroslavl, Russian Federation
    • Ra0123 410
• Slovakia
  • Bratislava, Slovakia
    • Ra0123 501
• United Kingdom
  • Glasgow, United Kingdom
    • Ra0123 601

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: CZP / CZP + PBO / CZP; 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; Pharmaceutical form: Prefilled syringes; Concentration: 200 mg/ml; Route of administration: Subcutaneous injection; Other: Placebo; Pharmaceutical form: Solution for infusion; Concentration: 0.9% saline; Route of administration: Intravenous infusion
Experimental: CZP / CZP + UCB4940 / CZP; 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: Certolizumab Pegol; Pharmaceutical form: Prefilled syringes; Concentration: 200 mg/ml; Route of administration: Subcutaneous injection; Biological: Bimekizumab; 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
Other: CZP / CZP/ CZP; Certolizumab Pegol (400 mg at Weeks 0, 2, and 4 followed by 200 mg every two Weeks) until Week 30	Biological: Certolizumab Pegol; Pharmaceutical form: Prefilled syringes; Concentration: 200 mg/ml; Route of administration: Subcutaneous injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: UCB Celltech
• Collaborators: PRA Health Sciences

Publications and helpful links

General Publications

• Glatt S, Taylor PC, McInnes IB, Schett G, Landewe R, Baeten D, Ionescu L, Strimenopoulou F, Watling MIL, Shaw S. Efficacy and safety of bimekizumab as add-on therapy for rheumatoid arthritis in patients with inadequate response to certolizumab pegol: a proof-of-concept study. Ann Rheum Dis. 2019 Aug;78(8):1033-1040. doi: 10.1136/annrheumdis-2018-214943. Epub 2019 Jun 8.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: April 27, 2015
• First Submitted That Met QC Criteria: April 29, 2015
• First Posted (Estimate): April 30, 2015

Study Record Updates

• Last Update Posted (Actual): May 31, 2017
• Last Update Submitted That Met QC Criteria: May 29, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Certolizumab Pegol
• Other Study ID Numbers: RA0123; 2014-003307-30 (EudraCT Number)