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Evaluation of the Effectiveness and Safety of Two Dosing Regimens of Olokizumab (OKZ), Compared to Placebo and Adalimumab, in Subjects With Rheumatoid Arthritis (RA) Who Are Taking Methotrexate But Have Active Disease (CREDO 2)

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ClinicalTrials.gov Identifier: NCT02760407
Recruitment Status : Recruiting
First Posted : May 3, 2016
Last Update Posted : December 3, 2018
Sponsor:
Collaborators:
Quintiles, Inc.
OCT Clinical Trials
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 May 2016
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 30, 2017)
ACR20 response [ Time Frame: 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
Original Primary Outcome Measures  ICMJE
 (submitted: May 2, 2016)
ACR20 response [ Time Frame: 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
Change History Complete list of historical versions of study NCT02760407 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 30, 2017)
  • ACR20 response and to demonstrate that the efficacy of OKZ is non-inferior to adalimumab [ Time Frame: 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.
  • 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: Baseline to Week 12 ]
    measured by the Health Assessment Questionnaire Disability Index (HAQ DI)
  • ACR50 response [ Time Frame: at Week 24 ]
    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 24
  • Simplified Disease Activity Index (SDAI) ≤3.3 (remission) [ Time Frame: at Week 24 ]
    Difference between OKZ and placebo in the percentage of subjects with SDAI ≤3.3 (remission) and remaining on randomized treatment and in the study at Week 24.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 2, 2016)
  • ACR20 response and to demonstrate that the efficacy of OKZ is non-inferior to adalimumab [ Time Frame: 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 non-inferior to adalimumab, provided that superiority of adalimumab to placebo (assay sensitivity) is demonstrated concurrently based on the same endpoint.
  • 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: Baseline to Week 14 ]
    measured by the Health Assessment Questionnaire Disability Index (HAQ DI)
  • ACR50 response [ Time Frame: at Week 24 ]
    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 24
  • Simplified Disease Activity Index (SDAI) ≤3.3 (remission) [ Time Frame: at Week 24 ]
    Difference between OKZ and placebo in the percentage of subjects with SDAI ≤3.3 (remission) and remaining on randomized treatment and in the study at Week 24.
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 and Adalimumab, in Subjects With Rheumatoid Arthritis (RA) Who Are Taking Methotrexate But Have Active Disease
Official Title  ICMJE 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
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 methotrexate (MTX).
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 MTX. 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. Adalimumab 40 mg q2w SC has been included as the active comparator for assay sensitivity and non inferiority evaluations.
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 64mg q4w
  • Drug: Olokizumab 64mg q2w
  • Drug: Adalimumab 40mg q2w
    Other Name: Humira
  • Drug: Placebo q2w
Study Arms  ICMJE
  • Experimental: Arm 1: Olokizumab q4w + Methotrexate
    Experimental, Olokizumab 64mg q4w Subcutaneous + Methotrexate (oral)
    Intervention: Drug: Olokizumab 64mg q4w
  • Experimental: Arm 2: Olokizumab q2w + Methotrexate
    Experimental, Olokizumab 64mg q2w Subcutaneous + Methotrexate (oral)
    Intervention: Drug: Olokizumab 64mg q2w
  • Active Comparator: Arm 3: Adalimumab q2w + Methotrexate
    Active Comparator, Adalimumab 40mg q2w Subcutaneous + Methotrexate (oral)
    Intervention: Drug: Adalimumab 40mg q2w
  • Placebo Comparator: Arm 4: Placebo q2w + Methotrexate
    Placebo Comparator, Placebo q2w Subcutaneous + 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)
1575
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion 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 12 weeks prior to Screening.
  • Inadequate response to 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 intolerant 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

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)
  • Prior use of bDMARDs
  • 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
  • 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 1.5 years 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
  • Uncontrolled diabetes mellitus
  • History of chronic alcohol or drug abuse as judged by the Investigator
  • Female subjects who are pregnant, currently lactating
  • Female subjects of childbearing potential 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, adalimumab, 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,   Bulgaria,   Brazil,   Colombia,   Czechia,   Estonia,   Germany,   Hungary,   Korea, Republic of,   Latvia,   Lithuania,   Mexico,   Poland,   Romania,   Russian Federation,   Taiwan,   United Kingdom,   United States
Removed Location Countries China,   Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02760407
Other Study ID Numbers  ICMJE CL04041023
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
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