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    The EU Clinical Trials Register currently displays   41467   clinical trials with a EudraCT protocol, of which   6815   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
     
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    Summary
    EudraCT Number:2008-006917-25
    Sponsor's Protocol Code Number:A3003RA
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2009-04-09
    Trial 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 ConcernedUK - MHRA
    A.2EudraCT number2008-006917-25
    A.3Full title of the trial
    A Phase II, Randomized Multi-Center, Double-Blind Study of Tranilast with Concomitant Methotrexate (MTX) Compared to MTX Alone in Patients with Active Rheumatoid Arthritis (RA).
    A.3.2Name or abbreviated title of the trial where available
    Tranilast plus Methotrexate vs MTX Alone in Patients with Active RA
    A.4.1Sponsor's protocol code numberA3003RA
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorNuon Therapeutics, Inc.
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 nameTranilast
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTranilast
    D.3.9.1CAS number 53902-12-8
    D.3.9.2Current sponsor codeNone
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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 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 nameTranilast
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTranilast
    D.3.9.1CAS number 53902-12-8
    D.3.9.2Current sponsor codeNone
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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: 3
    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 Yes
    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 namemethotrexate
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 59052
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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 placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Patients with active rheumatoid arthritis who are on a stable dose of methotrexate
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of tranilast at two different dosages compared to placebo in subjects with active RA when added to continuing methotrexate therapy.
    E.2.2Secondary objectives of the trial
    To evaluate the safety and tolerability of tranilast at two different dosages compared to placebo in patients with RA receiving concomitant treatment with MTX.
    To identify any significant differences in the safety or efficacy profile of the two doses of tranilast in subjects with RA when added to continuing MTX therapy.

    Pharmacokinetic objectives
    To determine the plasma concentrations of tranilast in subjects with RA receiving concomitant oral MTX therapy.

    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Sub-study 1
    The study includes a intensive Pharmacokinetics sub-study, version: original, date: 20 Oct 2008 (N.B. this is included within the main protocol)

    Objectives:
    1.To determine the plasma concentrations and pharmacokinetics of tranilast in subjects with active RA receving concomitant oral MTX therapy;
    2. To evaluate the potential for tranilast to affect the PK of orally administered MTX (intensive PK sub-study subjects only)

    Sub-study 2
    A Phase II, Randomized Multi-Center, Double-Blind Study of Tranilast with Concomitant Methotrexate (MTX) Compared to MTX Alone in Patients with Active Rheumatoid Arthritis (RA). An Exploratory Sub-study of Effect of Tranilast on Synovial Vascularity - Original: 16 Feb 2009, Amendment 1 16 Nov 2009

    Synovial Vascularity sub-study objective
    1. To examine the effect of tranilast on synovial vascularity and peripheral blood biomarkers when administered to active RA patients being co-administered a stable dose of oral methotrexate (MTX).

    Sub-study 3
    A Phase II, Randomized Multi-Center, Double-Blind Study of Tranilast with Concomitant Methotrexate (MTX) Compared to MTX Alone in Patients with Active Rheumatoid Arthritis (RA). An Exploratory Sub-study of Genotype on Susceptibility to Tranilast-induced Liver Injury - Original: 15 April 2010

    Pharmacogenomic sub-study objective
    To examine the potential association of genotype variants on susceptibility to tranilast-induced liver injury.
    E.3Principal inclusion criteria
    1. Signed and dated written Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved informed consent obtained from the subject in accordance with the local regulations;
    2. Male or female subjects, ≥18 to ≤75 years of age, who have a diagnosis of RA (using the American Rheumatism Association 1987 Revised Criteria) for at least 6 months prior to screening, and are Functional Class 1-3 (as defined by the 1991 Revised Criteria for the Classification of Global Functional Status in Rheumatoid Arthritis) at baseline;
    3. Subjects must be receiving MTX (oral or parenteral) at a dose of at least 10 mg/week for ≥6 months and at a stable dose and route of administration for ≥8 weeks prior to randomization (Day 0);
    4. Subjects must receive at least 5 mg of folic acid or folinic acid per week at a stable dose for at least 4 weeks prior to randomization (Day 0);
    5. Subjects must have at least 8 painful/tender and 6 swollen joints (based upon 68/66 joint counts) at screening and baseline (Day 0);
    6. Subjects must have an elevated CRP level (defined as > the upper limit of normal [ULN] for the central lab) or an elevated ESR (defined as > the upper limit of normal [ULN] for the local lab) at screening;
    7. Availability of normal chest X-ray within the last 6 months (i.e., no evidence of TB or chest infection). Patients who are clinically asymptomatic with minor changes consistent with rheumatoid lung are acceptable.
    8. Subjects may be receiving:
    • Oral steroids at a stable dose of <=10 mg/day of prednisone (or equivalent corticosteroid dose) if previously taken for at least one month prior to randomization (Day 0);
    • Chronic NSAIDs if taken at a stable dose for at least one month prior to randomization (occasional use of NSAIDs for relief of headaches menstrual cramps, and minor pain unrelated to RA is allowed);
    • Hydroxychloroquine if taken at a stable dose of 200-400 mg PO daily or chloroquine if taken at a stable dose of up to 250 mg PO daily for at least 3 months prior to randomization, with no evidence of ocular toxicity as documented by ophthalmologic exam within the previous 12 months;
    • Sulfasalazine if taken at a stable daily dose of up to 3000 mg for at least 3 months prior to randomization;
    9. Females of childbearing potential must agree to continue to use adequate contraception (i.e., hormonal [oral, depot, patch], IUD, or barrier and spermicide) throughout the study and for at least 1 month following their last study visit;
    10. In the opinion of the investigator, the subject will be compliant and have a high probability of completing the study and all required procedures.

    E.4Principal exclusion criteria
    1. Use of intra-articular corticosteroid injections within one month prior to randomization (Day 0);
    2. Use of other anti-arthritic treatments not mentioned in the above inclusion criteria, including approved or experimental oral, topical, or injectable biologics or drugs, or devices within 3 months or 5 half-lives (whichever is longer)prior to randomization (Day 0);
    3. Pregnant or nursing females;
    4. Subjects who have received prior treatment with tranilast;
    5. Subjects who have any known hypersensitivity to any of the excipients contained in the study drug formulation;
    6. Use of any of the following other medications: (a) oral hypoglycemic agents: tolbutamide, glipizide, glimepiride, glyburide, repaglinide, nateglinide, or a thiazolidenedione (“glitazones”, e.g. rosiglitazone); (b) warfarin or coumarol; (c) phenytoin, paclitaxel, fluconazole, amiodarone, or isoniazid; (d) a uricosuric agent for gout; or (e) an investigational medication or participation in an investigational study within 3 months of Day 0
    7. Subjects with any laboratory test at screening considered significantly abnormal. The following will be considered significantly abnormal:
    • alanine transaminase (ALT), aspartate transaminase (AST), or alkaline phosphatase >=1.25 times the upper limit of normal (ULN) or
    • cytopenia (to include any of the following: WBC <3.5x10cubed/μL; Hgb <10 g/dL; platelets <100x10cubed/μL; neutrophils absolute <1.5x10cubed/μL; lymphocytes absolute <0.8x10cubed/μL) or
    • Creatinine >=1.25 times the upper limit of normal (ULN)
    8. Has an elevated total bilirubin (e.g., outside the upper limit of normal), which persists upon repeat or a history of Gilbert’s syndrome;
    9. History of clinically significant renal or hepatic dysfunction or disease;
    10. Has a history of or has a current, clinically significant major psychiatric disorder
    (e.g., major depressive disorder, psychosis, schizophrenia) according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV TR) [Exception; subjects with depression that has been adequately controlled for at least 6 months may enroll in the study];
    11. Has a history of alcohol or drug dependence or abuse as defined by DSM IV TR criteria within the last 2 years;
    12. Has a history of uric acid urolithiasis or gout;
    13. Has a clinically significant systemic infection (e.g., chronic or acute infection, UTI, URI) within 30 days of Day 0, or a history or presence of recurrent or chronic infection
    (e.g., viral infections, including hepatitis B or C, HIV), bacterial infections, systemic fungal infections, or syphilis);
    14. Has evidence of tuberculosis as indicated by subjects with a positive tuberculin (TB) skin test at screening or within the 30 days prior to screening (defined as >=10 mm induration);
    15. Has any other significant medical disease, mental impairment or other clinically significant abnormality on physical, neurological, laboratory, vital signs or ECG examination that the investigator or Sponsor believes would be detrimental to the subject or compromise the study;
    16. Subject with any other condition, clinical finding, or reason that, in the opinion of the investigator and/or Sponsor, is determined to be unsuitable for enrollment into the study (e.g., subject with known compliance issues, geographical constraints for attending required clinic visits);
    17. Presence of, or history of cancer with the exception of completely excised, non-metastatic squamous cell and basal cell carcinomas of the skin
    18. Subjects planning or likely to require any surgical procedure during the study treatment period;

    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy analysis will utilize the Efficacy Population and compare the proportions (%) of subjects achieving an ACR20 response in the tranilast 300 mg/day group and the placebo group at Week 12. This analysis will utilize an LOCF approach and results will be utilized by the Sponsor to determine the efficacy potential for tranilast in RA.
    In addition, the primary endpoint will also be analyzed for the MITT population, but this will not be considered the primary efficacy analysis for this study. Non-responder imputation (all-cause dropouts and subjects with missing efficacy data at Week 12 are considered non-responders) will be utilized for this MITT population analysis
    These analyses will be performed using the Cochran-Mantel-Haenszel chi-square test with participation in the PK sub-study as a stratification factors. However, if any of the resultant cells for prior exposure to biologic treatments has <2 placebo patients, the Cochran-Mantel-Haenszel chi-square test will adjust only for geographic region. The null hypothesis of equality of ACR20 response rates will be assessed using a two-sided test at the 5% level of significance.
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA22
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    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
    End of trial has been defined by the sponsor as being completion of study report
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months2
    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 Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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 state36
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 155
    F.4.2.2In the whole clinical trial 250
    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 Decision2009-03-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-04-22
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2010-09-23
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