Study of the Efficacy and Safety of Olokizumab in Patients with Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Tumor Necrosis Factor Alpha (TNF-a) Inhibitor Therapy

• Register: EUCTR
• Last refreshed on: 26 March 2024
• Main ID: EUCTR2015-005308-27-CZ
• Date of registration: 15/04/2016
• Prospective Registration: Yes
• Primary sponsor: R-Pharm International LLC
• Public title: Study of the Efficacy and Safety of Olokizumab in Patients with Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Tumor Necrosis Factor Alpha (TNF-a) Inhibitor 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 Tumor Necrosis Factor Alpha (TNF-a) Inhibitor Therapy - Clinical Rheumatoid Arthritis Development for Olokizumab (CREDO) 3
• Date of first enrolment: 07/06/2016
• Target sample size: 350
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-005308-27
• 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

Argentina, Brazil, Colombia, Czech Republic, Germany, Hungary, Korea, Republic of, Mexico, Poland, United States

Contacts

• Name: Medical Department
• Affiliation: R-Pharm International LLC

• Name: Medical Department
• Affiliation: R-Pharm International LLC

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 24 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.Treatment with oral, SC, or intramuscular (IM) MTX for at least 12 weeks prior to Screening at a dose of 15 to 25 mg/week (or =10 mg/week if there is documented intolerance 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 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
6.Subjects must have a documented inadequate response to treatment (i.e., TNFi failure) with =1 licensed TNFi following at least 12 weeks of therapy with that agent. Inadequate response to treatment is classified as either:
a.Primary failure: The absence of any documented clinically significant response; or
b.Secondary failure: Documented initial response with subsequent loss of that response or partial response

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 350
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.Diagnosis of any other inflammatory arthritis or systemic rheumatic disease •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 Janus kinases and spleen tyrosine kinase [SYK] inhibitors)
4.Prior treatment with cell depleting therapies, including anti CD20 agents or investigational agents (e.g., CAMPATH, anti CD4, anti CD5, anti CD3, and anti CD19), with the exception of rituximab, which is allowed with a washout period of 24 weeks prior to baseline.
5.Use of parenteral and/or intra articular glucocorticoids within 4 weeks prior to baseline
6.Use of oral glucocorticoids greater than 10 mg/day prednisone (or equivalent) or change in dosage within 2 weeks prior to baseline
7.Prior history of no response to hydroxychloroquine and sulfasalazine
8.Prior use of cDMARDs other than MTX is allowed with the following washout periods to be completed prior to baseline:
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 a day for at least 24 hours
c.24 weeks for cyclophosphamide
9.Vaccination with live vaccines in the 6 weeks prior to baseline or planned vaccination with live vaccines during the study
10.Participation in any other investigational drug study within 30 days or 5 times the terminal half-life of the investigational drug, whichever is longer, prior to baseline
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

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

Moderately to Severely Active Rheumatoid Arthritis

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

Primary Outcome(s)

Primary end point(s): The primary efficacy endpoint is the American College of Rheumatology 20% (ACR20) response at Week 14, where a responder is defined as any subject satisfying ACR20 criteria and remaining on randomized treatment and in the study at Week 14. 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 assess exposure to OKZ
To assess the safety and tolerability of OKZ

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 TNF-a inhibitor (TNFi) therapy.

Timepoint(s) of evaluation of this end point: week 14

Secondary Outcome(s)

Secondary end point(s): •Difference between OKZ and placebo in the 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 14
•Difference between OKZ and placebo in the improvement of physical ability from baseline to Week 14, as measured by the Health Assessment Questionnaire Disability Index (HAQ DI)
•Difference between OKZ and placebo in the percentage of subjects achieving an American College of Rheumatology 50% (ACR50) response and remaining on randomized treatment and in the study at Week 14
•Difference between OKZ and placebo in the percentage of subjects with Simplified Disease Activity Index (SDAI) =3.3 (remission) and remaining on randomized treatment and in the study at Week 14

Timepoint(s) of evaluation of this end point: week 14
baseline to Week 14

Secondary ID(s)

CL04041025

Source(s) of Monetary Support

R-Pharm International LLC

Ethics review

Status: Approved
Approval date: 07/06/2016
Contact:

Results

• Results available: Yes
• Date Posted: 31/12/2020
• Date Completed: 01/10/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-005308-27/results