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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

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).

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Olokizumab 64mg q4w Drug: Olokizumab 64mg q2w Drug: Adalimumab 40mg q2w Drug: Placebo q2w Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1575 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official 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
Study Start Date : May 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : May 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 1: Olokizumab q4w + Methotrexate
Experimental, Olokizumab 64mg q4w Subcutaneous + Methotrexate (oral)
Drug: Olokizumab 64mg q4w
Experimental: Arm 2: Olokizumab q2w + Methotrexate
Experimental, Olokizumab 64mg q2w Subcutaneous + Methotrexate (oral)
Drug: Olokizumab 64mg q2w
Active Comparator: Arm 3: Adalimumab q2w + Methotrexate
Active Comparator, Adalimumab 40mg q2w Subcutaneous + Methotrexate (oral)
Drug: Adalimumab 40mg q2w
Other Name: Humira

Placebo Comparator: Arm 4: Placebo q2w + Methotrexate
Placebo Comparator, Placebo q2w Subcutaneous + Methotrexate (oral)
Drug: Placebo q2w



Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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)

  4. 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

  5. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02760407


  Show 267 Study Locations
Sponsors and Collaborators
R-Pharm
Quintiles, Inc.
OCT Clinical Trials
Investigators
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Study Director: Mikhail Samsonov R-Pharm

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Responsible Party: R-Pharm
ClinicalTrials.gov Identifier: NCT02760407     History of Changes
Other Study ID Numbers: CL04041023
First Posted: May 3, 2016    Key Record Dates
Last Update Posted: December 3, 2018
Last Verified: November 2018

Keywords provided by R-Pharm:
moderate Rheumatoid Arthritis
severe Rheumatoid Arthritis
subcutaneous
Olokizumab

Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Adalimumab
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents