Study of the Efficacy and Safety of Olokizumab in Patients with Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Methotrexate Therapy

• Register: EUCTR
• Last refreshed on: 16 December 2019
• Main ID: EUCTR2015-005307-83-LV
• Date of registration: 16/03/2016
• Prospective Registration: Yes
• Primary sponsor: R-Pharm
• Public title: Study of the Efficacy and Safety of Olokizumab in Patients with Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Methotrexate Therapy
• Scientific title: A Randomized, Double-Blind, Parallel-Group, Placebo- and Active-Controlled, Multicenter Phase III Study of the Efficacy and Safety of Olokizumab in Subjects with Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Methotrexate Therapy - Clinical Rheumatoid Arthritis Development for Olokizumab (CREDO) 2
• Date of first enrolment: 03/03/2017
• Target sample size: 1575
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-005307-83
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Brazil, Bulgaria, Colombia, Czech Republic, Estonia, Georgia, Germany, Hungary, Korea, Republic of, Latvia, Lithuania, Mexico, Poland, Romania, Russian Federation, Taiwan, United Kingdom, United States

Contacts

• Name: Medical Department
• Affiliation: JSC R-Pharm

• Name: Medical Department
• Affiliation: JSC R-Pharm

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female subjects =18 years of age
2. Subjects willing and able to sign informed consent
3. Subjects must have a diagnosis of adult-onset RA classified by ACR/EULAR 2010 revised classification criteria for RA for at least 12 weeks prior to Screening. If the subject was diagnosed according to ACR 1987 criteria previously, the Investigator may classify the subject per ACR 2010 retrospectively, using available source data.
4. Inadequate response to treatment with oral, SC, or intramuscular (IM) MTX (as defined by protocol) for at least 12 weeks prior to Screening at a dose of 15 to 25 mg/week (or =10 mg/week if intolerant to higher doses). The dose and means of administering MTX must have been stable for at least 6 weeks prior to Screening.
5. Subjects must be willing to take folic acid or equivalent throughout the study.
6. Subjects must have moderately to severely active RA disease as defined by all of the following:
a. =6 tender joints (68-joint count) at Screening and baseline; and
b. =6 swollen joints (66-joint count) at Screening and baseline; and
c. CRP above ULN at Screening based on the central laboratory results
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1345
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 230

Exclusion criteria:
1. Diagnosis of any other inflammatory arthritis or systemic rheumatic disease
(e.g., gout, psoriatic or reactive arthritis, Crohn’s disease, Lyme disease, juvenile
idiopathic arthritis, or systemic lupus erythematosus). However, subjects may have secondary Sjogren’s syndrome or hypothyroidism
2. Subjects who are Steinbrocker class IV functional capacity (incapacitated, largely or wholly bed-ridden or confined to a wheelchair, with little or no self-care)
3.Prior exposure to any licensed or investigational compound directly or indirectly targeting IL 6 or IL 6R (including tofacitinib or other Janus kinases and spleen tyrosine kinase [SYK] inhibitors)
4.Prior treatment with cell depleting therapies, including anti CD20 or investigational agents (e.g., CAMPATH, anti CD4, anti CD5, anti CD3, and anti CD19)
5. Prior use of bDMARDs
6. Use of parenteral and/or intra-articular glucocorticoids within 4 weeks prior to
baseline
7. Use of oral glucocorticoids greater than 10 mg/day prednisone (or equivalent) or change in dosage within 2 weeks prior to baseline
8. Prior documented history of no response to hydroxychloroquine and sulfasalazine
9. Prior use of cDMARDs (other than MTX) within the following windows prior to baseline (cDMARDs should not be discontinued to facilitate a subject’s participation in the study, but should instead have been previously discontinued as part of a subject’s medical management of RA):
a. 4 weeks for sulfasalazine, azathioprine, cyclosporine, hydroxychloroquine,
chloroquine, gold, penicillamine, minocycline, or doxycycline
b. 12 weeks for leflunomide unless the subject has completed the following elimination procedure at least 4 weeks prior to baseline: Cholestyramine at a dosage of 8 grams 3 times daily for at least 24 hours, or activated charcoal at a dosage of 50 grams 4 times daily for at least 24 hours
c. 24 weeks for cyclophosphamide
10. Vaccination with live vaccines in the 6 weeks prior to baseline or planned vaccination with live vaccines during the study

Please refer to the Protocol for the full list of exclusion criteria


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderately to Severely Active Rheumatoid Arthritis
MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Name: Olokizumab
Product Code: (CDP6038; L04041)
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Olokizumab
Other descriptive name: CDP6038
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 160-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Trade Name: Humira 40 mg solution for injection in pre-filled syringe
Product Name: Adalimumab (Humira®)
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Trade Name: Humira 40 mg solution for injection in pre-filled syringe
Product Name: Adalimumab (Humira®)
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Main Objective: The primary objective of this study is to evaluate the efficacy of olokizumab (OKZ) 64 mg administered subcutaneously (SC) once every 2 weeks (q2w) or once every 4 weeks (q4w) relative to placebo in subjects with moderately to severely active rheumatoid arthritis (RA) inadequately controlled by methotrexate (MTX) therapy.

Secondary Objective: ? To evaluate the efficacy of OKZ relative to adalimumab in subjects with moderately to severely active RA inadequately controlled by MTX therapy (for EU submission).
? To evaluate the efficacy of OKZ over time
? To compare the physical function and quality of life of subjects receiving OKZ relative to placebo
? To assess exposure to OKZ
? To assess the safety and tolerability of OKZ

Primary end point(s): The primary efficacy endpoint is the American College of Rheumatology 20% (ACR20) response at Week 12, where a responder is defined as any subject satisfying ACR20 criteria and remaining on randomized treatment and in the study at Week 12. This endpoint will serve to demonstrate that the efficacy of OKZ is superior to placebo.

Timepoint(s) of evaluation of this end point: week 12

Secondary Outcome(s)

Secondary end point(s): For EU submission: ACR20 response at Week 12, where a responder is defined as any subject satisfying ACR20 criteria and remaining on randomized treatment and in the study at Week 12. This endpoint will serve to demonstrate that the efficacy of OKZ is non-inferior to adalimumab, provided that superiority of adalimumab to placebo (assay sensitivity) is demonstrated concurrently based on the same endpoint
? Percentage of subjects achieving low disease activity, defined as Disease Activity Score 28-joint count (DAS28) C-reactive protein (CRP) <3.2, and remaining on randomized treatment and in the study at Week 12
? For EU submission: Percentage of subjects achieving low disease activity, defined as DAS28 (CRP) <3.2, and remaining on randomized treatment and in the study at Week 12. This endpoint will serve to demonstrate that the efficacy of OKZ is non-inferior to adalimumab, provided that superiority of adalimumab to placebo (assay sensitivity) is demonstrated concurrently based on the same endpoint
? Improvement of physical ability from baseline to Week 12, as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI)
? Percentage of subjects achieving an American College of Rheumatology 50% (ACR50) response and remaining on randomized treatment and in the study at Week 24
? Percentage of subjects with Clinical Disease Activity Index (CDAI) =2.8 (remission) and remaining on randomized treatment and in the study at Week 24

Timepoint(s) of evaluation of this end point: week 12, week 24

Secondary ID(s)

CL04041023

Source(s) of Monetary Support

R-Pharm

Ethics review

Status: Approved
Approval date:
Contact: