Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluation of the Long Term Safety, Tolerability and Efficacy of Two Dosing Regimens of Olokizumab (OKZ), in Subjects With Rheumatoid Arthritis (RA) Who Previously Completed 24 Weeks of Blinded Treatment in One of the Core Studies - CREDO 1, 2 or 3. (CREDO 4)

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: NCT03120949
Recruitment Status : Recruiting
First Posted : April 19, 2017
Last Update Posted : December 3, 2018
Sponsor:
Collaborators:
Quintiles, Inc.
OCT Clinical Trials
Mene Research
Information provided by (Responsible Party):
R-Pharm

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
The purpose of the study is to evaluate how safe, how effective and how well tolerated, the study drug Olokizumab is, in the long-term, in patients with Rheumatoid Arthritis (RA) who have previously taken part in and completed 24 weeks of blinded treatment in one of the core studies - CREDO 1, 2 or 3.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Olokizumab 64 mg SC q4w Drug: Olokizumab 64 mg SC q2w Drug: Methotrexate Phase 3

Detailed Description:
The goal of this Phase III study is to evaluate the long-term safety, tolerability, and efficacy of OKZ in subjects with moderately to severely active RA who previously completed 24 weeks of double-blind treatment with OKZ in the core studies. OKZ is expected to reduce the disease activity and induce an improvement in physical function. The study is expected to provide long-term safety information in a large group of subjects treated with OKZ for up to 106 weeks.
Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1880 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-Label, Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis
Actual Study Start Date : July 4, 2017
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : November 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Treatment Arm 1
Olokizumab 64 mg SC q4w + Methotrexate (oral)
 Drug: Olokizumab 64 mg SC q4w
Treatment Arm 1, Experimental, Olokizumab 64 mg Subcutaneous q4w + Methotrexate (oral)

Drug: Methotrexate

Treatment Arm 1, Experimental, Olokizumab 64 mg Subcutaneous q4w + Methotrexate (oral);

Treatment Arm 2, Experimental, Olokizumab 64 mg Subcutaneous q2w + Methotrexate (oral)
Experimental: Treatment Arm 2
Olokizumab 64 mg SC q2w + Methotrexate (oral)
 Drug: Olokizumab 64 mg SC q2w
Treatment Arm 2, Experimental, Olokizumab 64 mg Subcutaneous q2w + Methotrexate (oral)

Drug: Methotrexate

Treatment Arm 1, Experimental, Olokizumab 64 mg Subcutaneous q4w + Methotrexate (oral);

Treatment Arm 2, Experimental, Olokizumab 64 mg Subcutaneous q2w + Methotrexate (oral)


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Adverse events (AEs); Serious AEs (SAEs) and AEs of Special Interest (AESIs) [ Time Frame: Between 82-106 weeks ]
    Nature, incidence, severity, and outcome of AEs, including SAEs and AESIs

  2. Adjusted incidence rates (IR) and event rates (ER) [ Time Frame: Between 82-106 weeks ]
    Follow-up-adjusted IRs and ERs (per 100 subject-years [SY] of follow-up) for SAEs and AESIs

  3. Clinically significant laboratory abnormalities [ Time Frame: Between 82-106 weeks ]
    Proportions of subjects with clinically significant laboratory abnormalities

  4. Changes in clinical laboratory parameters, vital sign measurements, and physical examination findings [ Time Frame: Between 82-106 weeks ]
    Assessment of changes over time in clinical laboratory parameters, vital sign measurements, and physical examination findings expressed as the percentage of subjects who shift from normal/abnormal between baseline and post-treatment measurements.

  5. Occurrence of any major adverse cardiac event (MACE) [ Time Frame: Between 82-106 weeks ]
    Time from first exposure to OKZ to the first occurrence of any MACE

  6. Incidence and/or titer of antibodies [ Time Frame: Between 82-106 weeks ]
    Incidence and titer of antidrug antibodies (ADAs) to OKZ, incidence of neutralizing antibodies, and the time course of antibodies


Secondary Outcome Measures :
  1. American College of Rheumatology 20% (ACR20), ACR50, and ACR70 response [ Time Frame: Between 82-106 weeks ]
    Number of subjects achieving an ACR20, ACR50, and ACR70 response who remain on randomized open-label treatment and in the study

  2. American College of Rheumatology 20% (ACR20), ACR50, and ACR70 response [ Time Frame: Between 82-106 weeks ]
    Percentage of subjects achieving an ACR20, ACR50, and ACR70 response who remain on randomized open-label treatment and in the study

  3. Simplified Disease Activity Index (SDAI) ≤3.3 (remission) [ Time Frame: Between 82-106 weeks ]
    Proportion of subjects with SDAI ≤3.3 remission, who remain on randomized open-label treatment and in the study

  4. Proportion of subjects with Disease Activity Score 28-joint count (DAS28) low disease activity [ Time Frame: Between 82-106 weeks ]
    Proportion of subjects with Disease Activity Score 28-joint count (DAS28) low disease activity (based on DAS28 C-reactive protein [CRP] <3.2), who remain on randomized open-label treatment and in the study

  5. Changes in DAS28 (CRP) [ Time Frame: Between 82-106 weeks ]
    Change from baseline over time in DAS28 (CRP)

  6. Changes in Health Assessment Questionnaire-Disability Index (HAQ-DI) [ Time Frame: Between 82-106 weeks ]
    Change from baseline over time in the measure of physical ability based on HAQ-DI)

  7. Improvement in HAQ-DI [ Time Frame: Between 82-106 weeks ]
    Proportion of subjects with improvement from baseline in HAQ-DI score ≥0.22, who remain on randomized open-label treatment and in the study

  8. Changes in patient-reported outcome scores [ Time Frame: Between 82-106 weeks ]
    Change from baseline over time in the Short Form-36 (SF-36) Physical Component Summary (PCS) total score

  9. Changes in patient-reported outcome scores [ Time Frame: Between 82-106 weeks ]
    Change from baseline over time in the European Quality of Life-5 Dimensions (EQ-5D)

  10. Changes in patient-reported outcome scores [ Time Frame: Between 82-106 weeks ]
    Change from baseline over time in the Work Productivity Survey-Rheumatoid Arthritis (WPS-RA)

  11. Changes in patient-reported outcome scores [ Time Frame: Between 82-106 weeks ]
    Change from baseline over time in the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACITFatigue)

  12. Changes in SDAI and Clinical Disease Activity Index (CDAI) [ Time Frame: Between 82-106 weeks ]
    Change from baseline over time in SDAI and CDAI

  13. Responses for European League Against Rheumatism (EULAR) based on DAS28 (CRP) [ Time Frame: Between 82-106 weeks ]
    Proportion of subjects with moderate to good responses for EULAR based on DAS28 (CRP), who remain on randomized open-label treatment and in the study, assessed at all applicable time points, where a moderate response is defined as DAS28 (CRP) >3.2 and ≤5.1 with an improvement from baseline in DAS28 (CRP) >0.6 and ≤1.2, and a good response is defined as DAS28 (CRP) ≤3.2 with an improvement from baseline in DAS28 (CRP) >1.2

  14. Changes in components of American College of Rheumatology (ACR) Criteria [ Time Frame: Between 82-106 weeks ]
    Change from baseline to all time points in the components of the ACR response criteria

  15. Impact of ADAs to OKZ on subject safety and efficacy [ Time Frame: Between 82-106 weeks ]
    Impact of ADAs to OKZ on subject safety and efficacy Incidence of subjects showing antidrug antibodies (ADAs) to OKZ Number and percentage of subjects developing positive ADA titers over time

  16. Impact of ADAs to OKZ on subject safety and efficacy [ Time Frame: Between 82-106 weeks ]
    Impact of ADAs to OKZ on subject safety and efficacy ADA titers for OKZ Descriptive statistics for ADA titrations.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

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

  1. Subject must be willing and able to sign informed consent
  2. Subject must have completed the 24-week double-blind Treatment Period in 1 of the 3 core studies (CL04041022, CL04041023, or CL04041025).
  3. Subject must have maintained their stable dose (and route) of MTX 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) during the core study and plan to maintain the same dose and route of administration for additional 12 weeks
  4. Subjects must be willing to take folic acid or equivalent throughout the study.

Exclusion Criteria:

  1. Subject with any medically important condition in the core study (e.g., clinically significant laboratory values, frequent AEs or SAEs, infection SAEs, and/or other concurrent severe and/or uncontrolled medical condition) which would make this subject unsuitable for inclusion in the open-label extension (OLE) study in the Investigator's judgement.
  2. Subject has evidence of active tuberculosis (TB)
  3. Subject has planned surgery during the first 12 weeks of the OLE
  4. Female subjects who are pregnant or who are planning to become pregnant during the study or within 6 months of the last dose of study drug
  5. 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.
  6. Subject is unwilling or unable to follow the procedures outlined in the protocol
  7. Other medical or psychiatric conditions, or lab abnormalities that may increase the potential risk associated with study participation and administration of investigational medicinal products (IMPs), or that may affect study results interpretation and, as per Investigator's judgement, make the subject ineligible

The following restrictions may affect a subject's ability to participate in this study:

  • Availability to attend visits according to the protocol within the allowed window period
  • Ability to perform self-administration of study drug and availability of caregiver to administer study drug
  • Concomitant medication restrictions as described in the Informed Consent Form and protocol (water and concomitant medications are permitted) for at least 9 hours prior to all study visits 8. Subject with a positive or repeated indeterminate interferon-gamma release assay (IGRA) result at Week 22 of the core study

  • Subjects may be enrolled in the OLE study if they fulfill all 3 of the following criteria prior to the first dose of study treatment:

    1. Active TB is ruled out by a certified TB specialist or pulmonologist who is familiar with diagnosing and treating TB (as acceptable per local practice);
    2. The subject starts prophylaxis for LTBI according to country-specific/Centers for Disease Control and Prevention (CDC) guidelines (see Appendix 4 [Section 13.4]) (treatment with isoniazid for 6 months is not an appropriate

The Investigator (or designee) should review these restrictions with the subject during the Screening Period to determine any potential challenges in the subject's ability to comply with the protocol. Subjects not able to comply with the above mentioned restrictions should not be enrolled into the study.

Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT03120949


Locations
Show Show 304 study locations
Sponsors and Collaborators
R-Pharm
Quintiles, Inc.
OCT Clinical Trials
Mene Research
Investigators
Layout table for investigator information
Study Director: Mikhail Samsonov Chief Medical Officer, R-Pharm
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: R-Pharm
ClinicalTrials.gov Identifier: NCT03120949    
Other Study ID Numbers: CL04041024
2015-005309-35 ( EudraCT Number )
First Posted: April 19, 2017    Key Record Dates
Last Update Posted: December 3, 2018
Last Verified: November 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by R-Pharm:
Rheumatoid Arthritis
moderate
severe
 subcutaneous
Olokizumab
open-label
Additional relevant MeSH terms:
Layout table for MeSH terms
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
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