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    Summary
    EudraCT Number:2014-004996-22
    Sponsor's Protocol Code Number:7962-CL-0022
    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:2015-12-15
    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 number2014-004996-22
    A.3Full title of the trial
    A Phase 2a, Randomized, Double-blind, Placebo- and Naproxen-controlled, Parallel-group Study to Assess the Analgesic Efficacy of ASP7962 in Patients with Pain Due to Osteoarthritis of the Knee
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A trial to investigate the efficacy of ASP7692 in patients with pain due to arthritis in the knee
    A.4.1Sponsor's protocol code number7962-CL-0022
    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 SponsorAstellas Pharma Europe B.V.
    B.1.3.4CountryNetherlands
    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 supportAstellas Pharma Europe B.V.
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstellas Pharma Europe B.V.
    B.5.2Functional name of contact pointService Desk
    B.5.3 Address:
    B.5.3.1Street AddressSylviusweg 62
    B.5.3.2Town/ cityLeiden
    B.5.3.3Post code2333 BE
    B.5.3.4CountryNetherlands
    B.5.4Telephone number0031715455878
    B.5.5Fax number0031715455224
    B.5.6E-mailcontact@nl.astellas.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.3.2Product code ASP7962
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    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 INNASP7962
    D.3.9.3Other descriptive nameASP7962
    D.3.9.4EV Substance CodeSUB124281
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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) 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 No
    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 NAPROXEN Tablets USP
    D.2.1.1.2Name of the Marketing Authorisation holderTeva Pharmaceuticals USA Inc
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    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 INNNAPROXEN
    D.3.9.3Other descriptive nameNAPROXEN
    D.3.9.4EV Substance CodeSUB09159MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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) 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 No
    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
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule
    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
    Osteoarthritis of the knee
    E.1.1.1Medical condition in easily understood language
    Osteoarthritis of the knee
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10031165
    E.1.2Term Osteoarthritis knee
    E.1.2System Organ Class 100000004859
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Evaluate the analgesic efficacy of ASP7962 relative to placebo
    E.2.2Secondary objectives of the trial
    Secondary
    ● Evaluate the efficacy of ASP7962 relative to placebo on pain on walking, function and stiffness
    ● Evaluate the time course of efficacy of ASP7962 relative to placebo
    ● Evaluate the improvement in overall patient status of ASP7962 relative to placebo
    ● Evaluate the safety and tolerability of ASP7962 relative to placebo
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written Informed Consent and privacy language as per national regulations.
    2. Patient is a male or female patient and aged 18 to 80 years, at screening.
    3. Patient has a primary diagnosis of OA of the index knee with symptoms for at least 6 months prior to screening and patient meets American College of Rheumatology clinical classification criteria for OA of the knee, defined by the following.
    Knee pain and at least 3 of the following 6 (a-f):
    a) Age > 50 years
    b) Morning stiffness < 30 minutes
    c) Crepitus on active motion
    d) Bony tenderness
    e) Bony enlargement
    f) No palpable warmth of synovium
    4. Patient has a radiographic image of the index knee (according to the minimum quality criteria for radiographic image as set by the central radiology reader) showing evidence of OA with a Kellgren-Lawrence grade ≥ 2 at screening. (based on central reading).
    5. Patient has moderate to severe index knee pain (pain due to OA of the knee at least 5 days per week for the last 3 months prior to screening, as determined by patient’s medical history).
    6. Patient is ambulatory and the index knee must not contain any orthopedic and/or prosthetic device.
    7. WOMAC pain subscale score (with a 48-hour recall period) in the index knee ≥ 4 at baseline (visit 2 predose, mean of all questions on pain subscale).
    8. This criterion has been removed.
    9. WOMAC physical function subscale score ≥ 4 at baseline (visit 2 predose, mean of all questions on the physical function subscale with a 48-hour recall period).
    10. Patient is willing to discontinue all current pain medications during the baseline and treatment periods (until day 57) (except for allowed rescue medications). Low dose aspirin for cardioprophylaxis is allowed.
    11. Patient is compliant with daily pain recording.
    12. Male patient and their female spouse/partners who are of
    childbearing potential must be using a barrier method* and 1 form of
    highly effective birth control** starting at screening and continuing
    throughout the study period and for 90 days after the final study drug
    administration.
    13. Male patient must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration.
    14. Female patient must either:
    ● Be of non childbearing potential:
    ■ post-menopausal (defined as at least 1 year without any menses) prior to screening, or
    ■ documented surgically sterile
    ● Or, if of childbearing potential:
    ■ agree not to try to become pregnant during the study and for 28 days after the final study drug administration,
    ■ and have a negative pregnancy test at screening and at baseline (visit 2 predose),
    ■and, if heterosexually active, agree to consistently use a barrier
    method* and 1 form of highly effective birth control** starting at
    screening and continuing throughout the study period and for 28 days
    after the final study drug administration.
    15. Female patient must agree not to breastfeed starting at screening and continuing throughout the study period and for 28 days after the final study drug administration.
    16. Female patient must not donate ova starting at screening and continuing throughout the study period and for 28 days after the final study drug administration.
    17. Patient agrees not to participate in another investigational study from screening through the follow-up period (until day 57).

    * Barrier methods of birth control include:
    •Condom or occlusive cap (diaphragm or cervical/ vault caps) with
    spermicidal foam/gel/film/cream/suppository
    ** Highly effective forms of birth control include:
    •Consistent and correct usage of established oral contraception
    (including progestogen-only oral contraception associated with
    inhibition of ovulation).
    •Established intrauterine device (IUD) or intrauterine system (IUS).
    E.4Principal exclusion criteria
    3.Current or prior clinically significant neurologic disease, including but
    not limited to peripheral neuropathy, stroke, cognitive impairment and
    seizure.
    4.Any clinically significant uncontrolled musculoskeletal disorder (with
    the exception of OA), cardiovascular, gastrointestinal, endocrinologic
    (diabetes mellitus is allowed if controlled [glycated hemoglobin (HbA1c)
    ≤ 8.0%] and no peripheral neuropathy), hematologic, hepatic,
    immunologic, metabolic, urologic, pulmonary, dermatologic, renal
    and/or other major disease.
    5.Active malignancy or a history of malignancy (except for treated
    nonmelanoma skin cancer) within the past 5 years.
    6.History of inflammatory arthritis (including rheumatoid arthritis), or a
    history of RPOA (including osteonecrosis or avascular necrosis of bone
    and/or joints), or has other diagnoses that may increase the risk of
    RPOA, or severe knee malalignment or any other joint-related condition
    that makes the patient unsuitable for study participation.
    7.Findings suggestive of RPOA or increased risk for RPOA on screening
    radiographs of either index or non-index joints.
    8.History of shoulder surgery, clinically significant trauma or current
    symptoms, including pain or impaired range of motion at shoulder joint.
    9.Patient has a coagulopathy, is receiving anticoagulants or has been
    diagnosed with thrombocytopenia or a functional platelet disorder.
    10.History of paracetamol intolerance, or existence of medical condition
    or use of concomitant medication for which paracetamol is
    controindicated.
    11.Any contraindication to naproxen.
    12.Any contraindication to tramadol.
    15.a.Lifetime history of ischemic or hemorrhagic stroke, cardiac arrest,
    torsade de pointes, clinically significant structural heart disease or a
    personal or family history of long QT syndrome. b.Within 12 months
    prior to visit 2: acute coronary syndrome (e.g.,myocardial infarction,
    unstable angina [ischemic heart disease is allowed, if in the
    investigator's opinion, it is clinically stable]); transient ischemic attack;
    coronary or peripheral revascularization procedure; clinically significant
    cardiac arrhythmias (including atrial fibrillation or flutter), heart block
    (first degree heart block is allowed provided PR interval is not greater
    than 240 msec) or other clinically significant cardiovascular disorder.
    c.Current heart failure (NYHA class III and IV).
    16.Resting pulse rate < 50 or > 100 beats per minute (bpm); systolic
    blood pressure (SBP) > 160 mm Hg; diastolic blood pressure (DBP) > 90
    mm Hg at screening or baseline.
    17.History of unexplained syncopal events or has symptomatic
    orthostatic hypotension at screening or baseline, defined as postural
    related symptoms and at least one of the following: standing SBP ≥ 20
    mm Hg lower than supine SBP, standing DBP ≥ 10 mm Hg lower than
    supine DBP.
    19.Any liver tests (aspartate aminotransferase [AST], alanine
    aminotransferase [ALT], total bilirubin [TBL]) > 1.5 times the upper limit
    of normal [ULN] at screening.
    20.Estimated glomerular filtration rate of ≤ 60 mL/min/1.73m2 (MDRD
    calculation) at screening.
    23.Previously received antibodies to NGF within 3 months prior to
    screening.
    26.Received intra-articular corticosteroid or intra-articular local
    anesthetics within 3 months prior to screening, intra articular hyaluronic
    acid within 6 months prior to screening or any of these therapies during
    the screening or baseline periods.
    27.Received systemic corticosteroids within the past 30 days before
    screening or during the screening or baseline periods (topical, nasal and
    inhaled corticosteroids are permitted).
    28.Received any medications or nonmedication therapy with efficacy in
    reducing pain of OA of the knee, including over-the-counter (OTC)
    products (with the exception of ice packs, rest, and paracetamol) during
    the baseline period.
    29.Started or stopped physiotherapy, acupuncture or transcutaneous
    electrical nerve stimulation related to treatment of the index knee within
    4 weeks prior to screening or during the screening or baseline periods.
    Stable regimens of these therapies introduced more than 4 weeks prior
    to screening will be allowed if the regimen is to continue unchanged
    during the study.
    30.Used opioids for more than 4 days during the week preceding
    screening or during the screening period; or has received any opioids
    during the baseline period.
    31.Used dipeptidyl peptidase 4 (DPP-4) inhibitors within 12 months prior
    to visit 2.
    32.Regularly used any strong systemic inducer of cytochrome P450
    (CYP) 3A metabolism (e.g.,rifampin, St John's wort) in the 3 months
    before visit 2.
    36.Any painful condition syndrome (e.g.,neuropathy, fibromyalgia) or
    other concurrent medical or arthritic condition that has the potential to
    confound the assessment of pain in the index knee.
    E.5 End points
    E.5.1Primary end point(s)
    Change from baseline to week 4 in WOMAC pain subscale score
    E.5.1.1Timepoint(s) of evaluation of this end point
    week 4
    E.5.2Secondary end point(s)
    Secondary Efficacy Endpoints:
    Treatment Period
    • Change from baseline to EOT in WOMAC pain, physical function, and stiffness subscale scores, WOMAC total score, and WOMAC walking pain
    • Change from baseline to weeks 1 and 2 in WOMAC pain subscale score
    • Change from baseline to weeks 1, 2 and 4 in WOMAC physical function and stiffness subscale scores, WOMAC total score, and WOMAC walking pain
    • Change from baseline to EOT and to weeks 1, 2, 3 and 4 in mean daily average pain score assessed by the NRS in the patient’s daily diary
    • Change from baseline in overall patient improvement assessed by Patient Global Assessment (PGA) at EOT and weeks 1, 2 and 4
    • Proportion of patients that achieves ≥ 30% decrease from baseline to EOT in WOMAC pain subscale score
    • Proportion of patients that achieves ≥ 50% decrease from baseline to EOT in WOMAC pain subscale score
    Secondary Safety Endpoints
    ● Incidence and severity of TEAEs
    ● Vital signs, orthostatic challenge test
    ● Safety laboratory tests, including liver tests
    ● 12-lead ECG parameters
    ● Physical examination
    ● C-SSRS (evaluation of suicidal ideation and behavior).
    ● NPSI
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 1, week 2, week 3, week 4
    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) 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) Yes
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA33
    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 No
    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 years1
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    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: 150
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 55
    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 state120
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 205
    F.4.2.2In the whole clinical trial 205
    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)
    None
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-12-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-02-05
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-09-29
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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