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    Summary
    EudraCT Number:2015-005307-83
    Sponsor's Protocol Code Number:CL04041023
    National Competent Authority:Romania - National Agency for Medicines and Medical Devices
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-06-22
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedRomania - National Agency for Medicines and Medical Devices
    A.2EudraCT number2015-005307-83
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of the Efficacy and Safety of Olokizumab in Patients with Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Methotrexate Therapy
    A.3.2Name or abbreviated title of the trial where available
    Clinical Rheumatoid Arthritis Development for Olokizumab (CREDO) 2
    A.4.1Sponsor's protocol code numberCL04041023
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorR-Pharm
    B.1.3.4CountryRussian Federation
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportR-Pharm
    B.4.2CountryRussian Federation
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationR-Pharm
    B.5.2Functional name of contact pointMedical Department
    B.5.3 Address:
    B.5.3.1Street Address19-1, Berzarina Str
    B.5.3.2Town/ cityMoscow
    B.5.3.3Post code123154
    B.5.3.4CountryRussian Federation
    B.5.4Telephone number+7 495 956 7937
    B.5.5Fax number+7 495 956 7938
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameOlokizumab
    D.3.2Product code (CDP6038; L04041)
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOlokizumab
    D.3.9.3Other descriptive nameCDP6038
    D.3.9.4EV Substance CodeSUB32350
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number160
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Humira 40 mg solution for injection in pre-filled syringe
    D.2.1.1.2Name of the Marketing Authorisation holderAbbVie Ltd
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAdalimumab (Humira®)
    D.3.4Pharmaceutical form Solution for injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNADALIMUMAB
    D.3.9.1CAS number 331731-18-1
    D.3.9.4EV Substance CodeSUB20016
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Moderately to Severely Active Rheumatoid Arthritis
    E.1.1.1Medical condition in easily understood language
    Moderately to Severely Active Rheumatoid Arthritis
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.1
    E.1.2Level PT
    E.1.2Classification code 10039073
    E.1.2Term Rheumatoid arthritis
    E.1.2System Organ Class 10028395 - Musculoskeletal and connective tissue disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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 methotrexate (MTX) therapy.
    E.2.2Secondary objectives of the trial
     To evaluate the efficacy of OKZ relative to adalimumab in subjects with moderately to severely active RA inadequately controlled by MTX therapy (for EU submission).
     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
    E.2.3Trial contains a sub-study No
    E.3Principal 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 12 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. Inadequate response to treatment with oral, SC, or intramuscular (IM) MTX (as defined by protocol) 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.
    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
    E.4Principal exclusion criteria
    1. 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). 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. Treatment with any cell-depleting therapies including anti-CD20 or investigational agents (e.g., CAMPATH, anti-CD4, anti-CD5, anti-CD3, and anti-CD19)
    5. Past history of exposure to TNFi therapy
    6. Use of parenteral and/or intra-articular glucocorticoids within 4 weeks prior to
    baseline
    7. Use of oral glucocorticoids greater than 10 mg/day prednisone (or equivalent) or change in dosage within 2 weeks prior to baseline
    8. Prior history of no response to hydroxychloroquine and sulfasalazine
    9. Prior use of DMARDs 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
    10. Vaccination with live vaccines in the 6 weeks prior to baseline or planned vaccination with live vaccines during the study

    Please refer to the Protocol for the full list of exclusion criteria
    E.5 End points
    E.5.1Primary 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.
    E.5.1.1Timepoint(s) of evaluation of this end point
    week 14
    E.5.2Secondary end point(s)
     For EU submission: 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 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, 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 24
     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 24
    E.5.2.1Timepoint(s) of evaluation of this end point
    week 14, week 24
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial4
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA472
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Brazil
    Colombia
    Korea, Republic of
    Mexico
    Taiwan
    United States
    Estonia
    Latvia
    Lithuania
    Poland
    Bulgaria
    Romania
    Czechia
    Germany
    Hungary
    Russian Federation
    United Kingdom
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months2
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 1345
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 230
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state70
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 702
    F.4.2.2In the whole clinical trial 1575
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    After completion of the 24-week, double-blind Treatment Period, subjects will either roll over into the long-term OLE study or enter the safety Follow-Up Period.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-03-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-09-22
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-11-05
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