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: 29 April 2020
• Main ID: EUCTR2014-004719-36-BG
• Date of registration: 05/04/2016
• 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 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) 1
• Date of first enrolment: 14/05/2016
• Target sample size: 420
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004719-36
• 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: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belarus, Bulgaria, Russian Federation, Turkey

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 (see Protocol for definition of inadequate response to MTX treatment) 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 (68joint 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 375
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45

Exclusion criteria:
1. Diagnosis of any other inflammatory arthritis or systemic rheumatic
disease
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, with the following exception:
? Subjects who discontinued TNFi therapy due to a reason other than
lack of efficacy are allowed to enter the study (TNFi therapy 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). The use of TNFi therapy within the
following windows prior to baseline is exclusionary:
a. 4 weeks for etanercept
b. 8 weeks for infliximab
c. 10 weeks for adalimumab, certolizumab, and golimumab
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
For Full List please Refer to the Protocol


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

Health Condition(s) or Problem(s) studied

Moderately to Severely Active Rheumatoid Arthritis
MedDRA version: 19.0 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
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Olokizumab
Current Sponsor code: CDP6038
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

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.

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

Primary end point(s): The primary efficacy endpoint is the American College of Rheumatology
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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.

Secondary Objective: • 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 characterize population pharmacokinetics (PK) of OKZ and
individual drug exposures.
• To assess the safety and tolerability of OKZ.

Secondary Outcome(s)

Secondary end point(s): ? ? 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
? 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

Timepoint(s) of evaluation of this end point: Week 12/Week 24

Secondary ID(s)

CL04041022

Source(s) of Monetary Support

R-Pharm

Ethics review

Status: Approved
Approval date: 05/04/2016
Contact: