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    Summary
    EudraCT Number:2010-022205-17
    Sponsor's Protocol Code Number:H9B-MC-BCDM
    National Competent Authority:Lithuania - SMCA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2010-12-28
    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 ConcernedLithuania - SMCA
    A.2EudraCT number2010-022205-17
    A.3Full title of the trial
    A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of LY2127399 in Patients with Moderate to Severe Rheumatoid Arthritis (RA) who had an Inadequate Response to Methotrexate Therapy (FLEX-M)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Rheumatoid Arthritis Study in Patients on a Background Treatment of Methotrexate(FLEX-M)
    A.4.1Sponsor's protocol code numberH9B-MC-BCDM
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01198002
    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 SponsorEli Lilly and Company
    B.1.3.4CountryUnited States
    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 supportEli Lilly and Company
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationEli Lilly
    B.5.2Functional name of contact pointClinical Trial Information
    B.5.3 Address:
    B.5.3.1Street AddressN/A
    B.5.3.2Town/ cityN/A
    B.5.3.3Post codeN/A
    B.5.3.4CountryUnited States
    B.5.4Telephone numberN/A
    B.5.5Fax numberN/A
    B.5.6E-mailEU_Lilly_Clinical_Trials@lilly.com
    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 nameLY2127399
    D.3.2Product code LY2127399
    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 INNNot available
    D.3.9.1CAS number Not availabl
    D.3.9.2Current sponsor codeLY2127399
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number120
    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 Yes
    D.3.11.13.1Other medicinal product typeIgG4-variant monoclonal antibody
    D.IMP: 2
    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 nameLY2127399
    D.3.2Product code LY2127399
    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 INNNot available
    D.3.9.1CAS number Not availabl
    D.3.9.2Current sponsor codeLY2127399
    D.3.9.3Other descriptive nameNot available
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number90
    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 Yes
    D.3.11.13.1Other medicinal product typeIgG4-variant monoclonal antibody
    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
    Rheumatoid Arthritis
    E.1.1.1Medical condition in easily understood language
    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 14.0
    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 objectives of this study are to demonstrate, in patients on background MTX therapy, the superiority of 120 mg LY2127399 every 4 weeks (Q4W) (LY A) or 90 mg LY2127399 every 2 weeks (Q2W) (LY B), each after a loading dose, compared to placebo as follows:

     American College of Rheumatology 20% response rates (ACR20) at Week 24
     Structural progression as measured by van der Heijde modified Total Sharp Score (mTSS) at Week 52
     Health Assessment Questionnaire-Disability Index (HAQ-DI) scores at Week 24.
    E.2.2Secondary objectives of the trial
    The secondary objectives of the study are as follows:
    • To demonstrate, in patients on background MTX therapy, the superiority of LY A or LY B compared to placebo over 52 weeks
    • To evaluate structure (X-rays)
    • To evaluate the safety and tolerability of LY A or LY B compared to placebo.
    • To characterize the time course of change in absolute B cell counts, B cell subsets, and changes in serum Ig levels to treatment with LY2127399 versus placebo over 52 weeks.
    • To characterize the population PK of LY2127399 and explore PK/ PD relationships with efficacy, safety and biomarker endpoints.
    • To assess the potential development of anti LY2127399 antibodies and the impact on patient safety, efficacy, and PK of LY2127399.
    Additional exploratory measures will be studied, including:
    • To explore biomarkers that may be contained in serum, plasma, messenger ribonucleic acid (mRNA), and deoxyribonucleic acid (DNA) samples.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Male and female patients aged ≥18 years of age with a diagnosis of moderately to severely active adult onset RA
    • Diagnosis of Rheumatoid Arthritis (RA) of more than 6 months and less than 15 years
    • Regular use of methotrexate (MTX) in the past 12 weeks, with the dose being stable during the past 8 weeks
    • At least 8 tender and swollen joints
    • At least one erosion of a hand or foot joint observed on an X-ray
    • An abnormally high C-reactive protein (CRP) level or erythrocyte sedimentation rate (ESR)
    • Positive for Rheumatoid Factor (RF) or Anti-cyclic citrullinated peptide (CCP) antibody
    • Woman must not be pregnant, breastfeeding, or become pregnant during the study
    E.4Principal exclusion criteria
    • Use of unstable doses of non-steroidal inflammatory drugs (NSAIDS) in the past 6 weeks
    • Steroid injection or intravenous (iv) infusion in the last 6 weeks
    • Use of more than 10 mg/day of oral steroids in the last 6 weeks
    • History of an inadequate response to a biologic disease-modifying anti-rheumatic drug (DMARD)
    • History of a serious reaction to other biological DMARDs
    • History of the use of rituximab or other B cell therapy
    • Use of DMARDS other than MTX, hydroxychloroquine, or sulfasalazine within the last 8 weeks
    • Use of leflunomide within the last 12 weeks (unless cholestyramine was used to speed up the elimination of leflunomide)
    • Surgery on a joint or other major surgery less than 2 months ago, or plans to have joint surgery or major surgery during the study
    • Active fibromyalgia, juvenile chronic arthritis, spondyloarthropathy, Crohn's disease, ulcerative colitis, psoriatic arthritis, or other systemic inflammatory condition except RA
    • Cervical cancer or squamous skin cancer within the past 3 years, or other cancer within the past 5 years
    • Received a live vaccine received within the past 12 weeks (for example, vaccines for measles, mumps, rubella, and chicken pox, and nasal-spray flu vaccines)
    • Hepatitis or HIV
    • A serious bacterial infection (for example, pneumonia or cellulitis) within 3 months or a serious bone or joint infection within 6 months
    • Symptoms of herpes zoster or herpes simplex within the last month
    • Active or latent tuberculosis (TB)
    • Current symptoms of a serious disorder or illness
    • Use of an investigational drug within the last month
    • History of the use of rituximab, any other B cell targeted biotherapy, or denosumab
    E.5 End points
    E.5.1Primary end point(s)
    • Percentage of patients with American College of Rheumatology 20% response (ACR20) at Week 24
    • Change from baseline to Week 52 in van der Heijde modified Total Sharp Score (mTSS)
    • Change from baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI)
    • Percentage of patients with American College of Rheumatology 50% (ACR50) and 70% (ACR70) response
    • Change from baseline in Disease Activity Score C-Reactive Protein (DAS28-CRP)
    • Percentage of patients with DAS28-Based European League Against Rheumatism (EULAR) response
    • Change from baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) domain scores and summary scores
    • Change from baseline in Brief Fatigue Inventory (BFI) individual items and impact score
    • Change from baseline in duration of morning stiffness (minutes)
    • Percentage of patients with Major Clinical Response (MCR) during 52 weeks
    • Percentage of patients with change from baseline in mTSS less than or equal to 0
    • Change from baseline in B cell subset counts
    • Population Pharmacokinetics (PK)
    • Percentage of patients developing anti-LY2127399 antibodies
    • Change from baseline in Brief Pain Inventory Short Form (BPI-sf) individual items and interference scores
    • Percentage of patients with structural inhibition at Week 52
    • Change from baseline in mTSS
    • Change from baseline in serum immunoglobulin (Ig) levels
    • Change from baseline in joint space narrowing score and bone erosions score (components of mTSS)
    • Mean percent improvement in ACR N
    • Change from baseline in Tender Joint Count (68 joint count)
    • Change from baseline in Swollen Joint Count (66 joint count)
    • Change from baseline in Patient's Assessment of Pain (VAS)
    • Change from baseline in Patient's Global Assessment of Disease Activity (VAS)
    • Change from baseline in Physician's Global Assessment of Disease Activity (VAS)
    • Change from baseline to Week 52 in HAQ-DI
    • Change from baseline in absolute B cell counts
    • Percentage of patients with ACR20 at Week 52
    • Time to ACR20 response
    E.5.1.1Timepoint(s) of evaluation of this end point
    100 weeks
    E.5.2Secondary end point(s)
    •Percentage of patients with American College of Rheumatology 50% (ACR50) and 70% (ACR70) response
    •Change from baseline in Disease Activity Score C-Reactive Protein (DAS28-CRP)
    •Percentage of patients with DAS28-Based European League Against Rheumatism (EULAR) response
    •Change from baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) domain scores and summary scores
    •Change from baseline in Brief Fatigue Inventory (BFI) individual items and impact score
    •Change from baseline in duration of morning stiffness (minutes)
    •Percentage of patients with Major Clinical Response (MCR) during 52 weeks
    •Percentage of patients with change from baseline in mTSS less than or equal to 0
    •Change from baseline in B cell subset counts
    •Population Pharmacokinetics (PK)
    •Percentage of patients developing anti-LY2127399 antibodies
    •Change from baseline in Brief Pain Inventory Short Form (BPI-sf) individual items and interference scores
    •Percentage of patients with structural inhibition at Week 52
    •Change from baseline in mTSS
    •Change from baseline in serum immunoglobulin (Ig) levels
    •Change from baseline in joint space narrowing score and bone erosions score (components of mTSS)
    •Mean percent improvement in ACR N
    •Change from baseline in Tender Joint Count (68 joint count)
    •Change from baseline in Swollen Joint Count (66 joint count)
    •Change from baseline in Patient's Assessment of Pain (VAS)
    •Change from baseline in Patient's Global Assessment of Disease Activity (VAS)
    •Change from baseline in Physician's Global Assessment of Disease Activity (VAS)
    •Change from baseline to Week 52 in HAQ-DI
    •Change from baseline in absolute B cell counts
    •Percentage of patients with ACR20 at Week 52
    •Time to ACR20 response
    •Change from baseline in CRP
    E.5.2.1Timepoint(s) of evaluation of this end point
    100 weeks
    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 Yes
    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 trial3
    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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA52
    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
    Australia
    Brazil
    Bulgaria
    Colombia
    Croatia
    Hungary
    India
    Japan
    Korea, Republic of
    Lithuania
    Malaysia
    Mexico
    New Zealand
    Peru
    Poland
    Romania
    Russian Federation
    Slovakia
    South Africa
    Sri Lanka
    Taiwan
    Ukraine
    United States
    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
    As per protocol
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months3
    E.8.9.2In all countries concerned by the trial days0
    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: 886
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 104
    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 state26
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 497
    F.4.2.2In the whole clinical trial 990
    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)
    Patients who complete this study through to Week 100 may be eligible to continue receiving study drug in an open label extension study, protocol H9B-MC-BCDP.
    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 Decision2011-04-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-03-21
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2014-01-21
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