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    Summary
    EudraCT Number:2008-008237-11
    Sponsor's Protocol Code Number:RR08/8797
    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:2010-07-29
    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 ConcernedUK - MHRA
    A.2EudraCT number2008-008237-11
    A.3Full title of the trial
    An open label study to assess the effectiveness of oral methotrexate in reducing pain in knee osteoarthritis
    A.3.2Name or abbreviated title of the trial where available
    Pain Reduction in Osteoarthritis using oral Methotrexate
    A.4.1Sponsor's protocol code numberRR08/8797
    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 SponsorUniversity of Leeds
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    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 Information not present in EudraCT
    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.3.8INN - Proposed INNMETHOTREXATE
    D.3.9.1CAS number 59052
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.5mg
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Painful osteoarthritis of the knee joint.
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10023476
    E.1.2Term Knee osteoarthritis
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Primary outcome:
    Change in WOMAC pain score at 24 weeks (Western Ontario and McMasters Universities Index)

    To judge the effectiveness of methotrexate at reducing pain in the osteoarthritic knee joint after 24 weeks of treatment, by reducing synovitis in the joint.
    E.2.2Secondary objectives of the trial
    1) Changes on ultrasound scan at baseline and 24 weeks. Ultrasound images will be scored for synovitis.
    2) Change in OAQoL score (osteoarthritis quality of life score)
    3) Change in HADS score (hospital anxiety and depression score)
    4) Change in other WOMAC subscales (stiffness and function)
    5) Change in West Haven-Yale Multidimensional Pain Inventory scores
    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 of knee osteoarthritis
    Version 3.1. 2nd, March 2009.

    Various scientific hypotheses will be tested in a biological sub-study. As part of an in-house investigation of biomarkers, serum, plasma and DNA will be collected and stored from blood samples taken on the same day as the knee ultrasound scan, i.e. at baseline and 24 weeks, for assessment of auto-antibodies, inflammatory, vascular, synovial, cartilage and bone markers in this and future studies (subject to further ethical review of such studies).
    E.3Principal inclusion criteria
    1. Knee pain on most days in the last 3 months.

    2. Insufficient pain relief from, or inability to tolerate NSAIDs and/or opioids.

    3. Patient able to identify a predominantly painful knee (the signal knee).

    4. Moderate to severe pain of the signal knee as defined by a score of ≥40mm on a VAS (0-100mm) using the question “On average, how would you rate your knee pain during the last 3 months?”

    5. Fulfil clinical ACR Criteria for knee OA.

    6. A previous radiograph (X-Ray) of the signal knee with changes consistent with osteoarthritis.

    7. Men and women must use adequate birth control measures (e.g. abstinence, oral contraceptives, Intra-uterine device, barrier method with spermicide, or surgical sterilisation) for the duration of the study and should continue such precautions for 6 months after receiving the last infusion or dose of methotrexate. If female and have potential for child bearing then a negative pregnancy test must be performed prior to starting treatment.

    8. The patient must be able to adhere to the study visit schedule and other protocol requirements.

    9. The patient must be capable of giving informed consent and the consent must be obtained prior to any screening procedures.
    E.4Principal exclusion criteria
    1.1. The presence of any rheumatic diseases that could be responsible for secondary osteoarthritis.
    2. Use of intra-articular hyaluronic acid in the signal knee within the 6 months preceding enrolment in the study
    3. The use of oral, parenteral, intra-articular or intra-muscular steroids in the 2 months preceding enrolment into the study
    4. Knee injury, diagnostic arthroscopy or knee surgery within the 3 months preceding enrolment in the study
    5. The presence of non-OA causes of pain in the signal knee, e.g. referred hip pain, osteonecrosis.
    6. Women who are pregnant, nursing, or men or women planning pregnancy within 12 months after screening (i.e. approximately 6 months following last study medications).
    7. Use of any investigational (unlicensed) drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longer.

    8. Significant haematological or biochemical abnormality

    a. Haemoglobin 8.5 g/dL
    b. WCC 3.5 x 109/L
    c. Neutrophils 1.5 x 109/L
    d. Platelets 100 x 109/L
    e. ALT 2 times ULN for the laboratory conducting the test.
    f. Creatinine > 1.5 times ULN for the laboratory conducting the test


    9. Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease.

    10. Intake of alcohol above the recommended government guidelines (2 units per day for women, 3 units per day for men).

    11. Poor tolerability of venepuncture or lack of adequate venous access for required blood sampling during the study period.
    E.5 End points
    E.5.1Primary end point(s)
    The end points are defined as:
    • Completion of 24 weeks in the study
    • Withdrawal due to any reason
    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 No
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    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) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised Information not present in EudraCT
    E.8.1.2Open Information not present in EudraCT
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Information not present in EudraCT
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    open label
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    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 No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.7Trial has a data monitoring committee No
    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
    The last visit of the last subject in the trial
    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 months6
    E.8.9.1In the Member State concerned days
    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 state30
    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)
    Provided in protocol
    Standard care for osteoarthritis patients
    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 Decision2009-05-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-03-26
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2011-02-09
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