Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluation of the Effectiveness and Safety of Two Dosing Regimens of Olokizumab (OKZ), Compared to Placebo, in Subjects With Rheumatoid Arthritis (RA) Who Are Taking an Existing Medication Called a Tumour Necrosis Factor Alpha Inhibitor But Have Active Disease (CREDO 3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02760433
Recruitment Status : Recruiting
First Posted : May 3, 2016
Last Update Posted : December 3, 2018
Sponsor:
Collaborators:
Quintiles, Inc.
OCT Clinical Trials
Mene Research
Information provided by (Responsible Party):
R-Pharm

Tracking Information
First Submitted Date  ICMJE April 29, 2016
First Posted Date  ICMJE May 3, 2016
Last Update Posted Date December 3, 2018
Study Start Date  ICMJE December 2016
Estimated Primary Completion Date September 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 1, 2017)
ACR20 response [ Time Frame: at Week 12 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 2, 2016)
ACR20 response [ Time Frame: at Week 14 ]
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.
Change History Complete list of historical versions of study NCT02760433 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 1, 2017)
  • Difference between OKZ and placebo in the percentage of subjects achieving low disease activity [ Time Frame: at Week 12 ]
    Defined as DAS28 (CRP) <3.2, and remaining on randomized treatment and in the study at Week 12.
  • Difference between OKZ and placebo in the improvement of physical ability [ Time Frame: at Week 12 ]
    As measured by the Health Assessment Questionnaire Disability Index (HAQ DI)
  • ACR50 response [ Time Frame: at Week 12 ]
    Difference between OKZ and placebo in the percentage of subjects achieving an ACR50 response and remaining on randomized treatment and in the study at Week 12.
  • Simplified Disease Activity Index (SDAI) ≤3.3 (remission) [ Time Frame: at Week 12 ]
    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 12.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 2, 2016)
  • Difference between OKZ and placebo in the percentage of subjects achieving low disease activity [ Time Frame: at Week 14 ]
    Defined as DAS28 (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 [ Time Frame: at Week 14 ]
    As measured by the Health Assessment Questionnaire Disability Index (HAQ DI)
  • ACR50 response [ Time Frame: at Week 14 ]
    Difference between OKZ and placebo in the percentage of subjects achieving an ACR50 response and remaining on randomized treatment and in the study at Week 14.
  • Simplified Disease Activity Index (SDAI) ≤3.3 (remission) [ Time Frame: 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of the Effectiveness and Safety of Two Dosing Regimens of Olokizumab (OKZ), Compared to Placebo, in Subjects With Rheumatoid Arthritis (RA) Who Are Taking an Existing Medication Called a Tumour Necrosis Factor Alpha Inhibitor But Have Active Disease
Official Title  ICMJE 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-α) Inhibitor Therapy
Brief Summary The purpose of this study is to determine how safe and effective the study drug Olokizumab is, in patients with Rheumatoid Arthritis (RA) who are already receiving, but not fully responding to treatment with an existing medication called a tumour necrosis factor alpha inhibitor
Detailed Description The goal of this Phase III study is to assess the safety, tolerability, and efficacy of OKZ in subjects with moderately to severely active RA who have responded inadequately to TNFi therapy. The primary endpoint of the trial is at Week 12. Olokizumab is expected to reduce the disease activity and improve physical function. The study is expected to provide safety information in a large group of subjects over at least a 24 week period.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Drug: Olokizumab q4w
  • Drug: Olokizumab q2w
  • Drug: Placebo q2w
Study Arms  ICMJE
  • Experimental: Arm 1: Olokizumab q4w + Methotrexate
    Olokizumab 64 mg Subcutaneous q4w + Methotrexate (oral)
    Intervention: Drug: Olokizumab q4w
  • Experimental: Arm 2: Olokizumab q2w + Methotrexate
    Olokizumab 64 mg Subcutaneous q2w + Methotrexate (oral)
    Intervention: Drug: Olokizumab q2w
  • Placebo Comparator: Arm 3: Placebo q2w + Methotrexate
    Placebo Subcutaneous q2w + Methotrexate (oral)
    Intervention: Drug: Placebo q2w
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 2, 2016)
350
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2020
Estimated Primary Completion Date September 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Subjects may be enrolled in the study only if they meet all of the following criteria.

  • Subjects willing and able to sign informed consent
  • 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.
  • Treatment with 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.
  • Subjects must be willing to take folic acid or equivalent throughout the study.
  • Subjects must have moderately to severely active RA disease as defined by all of the following:

    • ≥6 tender joints (68 joint count) at Screening and baseline; and
    • ≥6 swollen joints (66 joint count) at Screening and baseline; and
    • CRP above ULN at Screening based on the central laboratory results.
  • 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.

Exclusion Criteria:

  • 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)
  • 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)
  • Prior treatment with cell depleting therapies including anti CD20 or investigational agents (e.g., CAMPATH, anti CD4, anti CD5, anti CD3, and anti CD19) with the exception of rituximab, which is allowed if it was discontinued at least 24 weeks prior to baseline (rituximab 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).
  • Prior use of bDMARDs, within the following windows prior to baseline (bDMARDs 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):

    1. 4 weeks for etanercept and anakinra
    2. 8 weeks for infliximab
    3. 10 weeks for adalimumab, certolizumab, and golimumab
    4. 12 weeks for abatacept
  • Use of oral glucocorticoids greater than 10 mg/day prednisone (or equivalent) or change in dosage within 2 weeks prior to baseline
  • Prior history of no response to hydroxychloroquine and sulfasalazine
  • 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):

    1. 4 weeks for sulfasalazine, azathioprine, cyclosporine, hydroxychloroquine, chloroquine, gold, penicillamine, minocycline, or doxycycline
    2. 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
    3. 24 weeks for cyclophosphamide
  • 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
  • Other treatments for RA (e.g., Prosorba Device/Column) within 6 months prior to baseline
  • Use of non steroidal anti inflammatory drugs (NSAIDs) on unstable dose or switching of NSAIDs within 2 weeks prior to baseline
  • Previous participation in this study (randomized) or another study of OKZ
  • Abnormal laboratory values
  • Subjects with concurrent acute or chronic viral Hepatitis B or C infection
  • Subjects with HIV infection
  • Subjects with:

    1. Current active TB disease or a history of active TB disease.
    2. Close contact with an individual with active TB within 1.5yrs prior to Screening
    3. History of untreated latent TB infection (LTBI), regardless of IGRA result at Screening
    4. Positive interferon-gamma release assay (IGRA) result at Screening. If indeterminate, the IGRA can be repeated once during the Screening Period. If there is a second indeterminate result, the subject will be excluded.
  • Concurrent malignancy or a history of malignancy within the last 5 years
  • History of chronic alcohol or drug abuse as judged by the Investigator
  • Female subjects who are pregnant, currently lactating,
  • Female subjects of childbearing who are not willing to use a highly effective method of contraception during the study OR Male subjects with partners of childbearing potential not willing to use a highly effective method of contraception during the study.
  • Subjects with a known hypersensitivity to any component of the OKZ drug product or placebo
  • Other exclusion criteria may apply
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Argentina,   Brazil,   Colombia,   Czechia,   Germany,   Hungary,   Korea, Republic of,   Mexico,   Poland,   Russian Federation,   Turkey,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02760433
Other Study ID Numbers  ICMJE CL04041025
2015-005308-27 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party R-Pharm
Study Sponsor  ICMJE R-Pharm
Collaborators  ICMJE
  • Quintiles, Inc.
  • OCT Clinical Trials
  • Mene Research
Investigators  ICMJE
Study Director: Mikhail Samsonov R-Pharm
PRS Account R-Pharm
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP