Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   35474   clinical trials with a EudraCT protocol, of which   5826   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).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2014-004805-34
    Sponsor's Protocol Code Number:TDU13828-ACT13830
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-12-10
    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 ConcernedGermany - BfArM
    A.2EudraCT number2014-004805-34
    A.3Full title of the trial
    A Two Part Protocol Using Double Blind Placebo Control to Assess the Safety, Tolerability, and Pharmacokinetics of Single Escalating Intra-articular Doses Followed by Assessment of Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Intra-articular Dose of the TrkA Inhibitor, GZ389988A, in Patients with Painful Osteoarthritis of the Knee
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    TDU13828: First-in-human Study with Ascending Single Intra-articular Doses of GZ389988A in Patients with Painful Osteoarthritis of the Knee

    ACT13830: Proof-of-concept Study to Assess the Efficacy, Tolerability and Safety of a Single Intra-articular Dose of GZ38998A versus Placebo in Patients with Painful Osteoarthritis of the Knee
    A.4.1Sponsor's protocol code numberTDU13828-ACT13830
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1163-0806
    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 SponsorSanofi-aventis Research & Development
    B.1.3.4CountryFrance
    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 supportSanofi-aventis Research & Development
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSanofi-Aventis Deutschland GmbH
    B.5.2Functional name of contact point
    B.5.3.4CountryGermany
    B.5.6E-mailmedinfo.de@sanofi.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 GZ389988A
    D.3.4Pharmaceutical form Suspension for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntraarticular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeGZ389988A
    D.3.9.4EV Substance CodeSUB169952
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 placeboSolvent for parenteral use
    D.8.4Route of administration of the placeboIntraarticular use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Osteoarthritis
    E.1.1.1Medical condition in easily understood language
    Osteoarthritis
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10031161
    E.1.2Term Osteoarthritis
    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
    TDU13828: To assess the safety and tolerability of ascending single intra-articular doses of GZ389988A in patients with painful osteoarthritis (OA) of the knee.

    ACT13830: To assess the efficacy of a single intra-articular dose of GZ389988A compared to placebo for relief of knee pain in patients with osteoarthritis (OA) of the knee
    E.2.2Secondary objectives of the trial
    TDU13828: To assess the pharmacokinetic parameters of ascending single intra-articular doses of GZ389988A in patients with painful OA of the knee.
    To obtain preliminary pharmacodynamics evaluation of ascending single intra-articular doses of GZ389988A in patients with painful OA of the knee.
    ACT13830: To assess the safety and tolerability of a single intra-articular dose of GZ389988A in patients with painful OA of the knee.
    To assess the pharmacokinetic parameters of a single intra-articular dose of GZ389988A in patients with painful OA of the knee.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    TDU13828:
    Men or women 40 to 60 years of age.
    Diagnosis of primary knee osteoarthritis, based upon the following:
    - Fulfilling the American College of Rheumatology Clinical and
    Radiographic criteria for OA (at least knee pain and osteophytes), with - X-ray or magnetic resonance imagng (MRI) evidence within the last 6 months for Kellgren and Lawrence classification II to IV.
    - Western Ontario and Mcmaster Universities Arthrities Index (WOMAC)
    A1 Pain subscore (walking pain) between 50 and 90 using the 100-mm visual analogue scale (VAS), corresponding to moderate to severe pain in the index knee, at both screening and baseline assessments at least 48 hours apart.
    Symptomatic for more than 6 months (if both symptomatic knees, at least for the most painful knee that will receive the study drug).
    Having given written informed consent prior to any procedure related to the study.
    Ambulatory with an active lifestyle and in good general health. (Assistive devices were allowed if used throughout a period of 3 months or more prior to screening, on the condition that they continued to be used throughout the study.)

    ACT13830:

    Men or women 40 to 80 years of age.
    Diagnosis of primary knee OA, based upon the following:
    - Fulfilling the American College of Rheumatology Clinical and
    Radiographic criteria for OA (at least knee pain and osteophytes), with
    - X-ray evidence within the last 6 months for Kellgren and Lawrence
    classification II to IV.
    - Western Ontario and McMaster Universities Arthritis Index (WOMAC)
    A1 Pain subscore (walking pain) over the last 48 hours ≥ 40 and ≤ 90 on
    VAS 0-100 in the target knee at screening with or without medication,
    and ≤ 30 on VAS 0-100 in the contralateral knee at screening with or
    without medication.
    - WOMAC A1 pain subscore (walking pain) between 50 and 90 using the
    VAS 0-100, corresponding to moderate to severe pain in the target knee
    at baseline (from eDiary, average of at least 3 days in the time window
    between Day-5 and Day-1).
    Symptomatic for more than 6 months (if both symptomatic knees, at
    least for the most painful knee that will receive the study drug).
    Having given written informed consent prior to any procedure related to
    the study.
    Ambulatory with an active lifestyle and in good general health. (Assistive
    devices were allowed if used throughout a period of 3 months or more
    prior to screening, on the condition that they continue to be used
    throughout the study).
    A male who is sexually active must use a condom as part of a method of
    highly effective contraception (eg, condom + spermicide, and an
    additional contraceptive method used by the partner) during sexual
    intercourse with a women of childbearing potential for the duration of
    the study period up to the end-of-study visit and should not father a
    child in this period. Male patients also have to agree not to donate sperm
    for the duration of the study until the end-of-study visit.
    E.4Principal exclusion criteria
    TDU13828:
    Women of child bearing potential.
    Any uncontrolled, chronic condition or laboratory finding which, in the opinion of the Investigator, could potentially put the patient at increased risk.
    Patients with clinically significant or uncontrolled hepatic,
    gastrointestinal, cardiovascular, respiratory, neurological (including diabetic neuropathy), psychiatric, hematological, renal, or dermatological disease, or any other medical condition that might interfere with the evaluation of the investigational medicinal product (IMP) according to Investigator's medical judgment.
    Chondrocalcinosis.
    Fibromyalgia.
    Major depression.
    History or presence of drug or alcohol abuse (alcohol consumption >40 grams per day).
    Any patient who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development.
    Abnormal coagulation parameters: outside the range international normalized ratio (INR) 0.85-1.15, activated partial thromboplastin time
    >33 seconds, platelets <140x10^9 /L.
    Moderate to severe renal impairment.
    Underlying hepatobiliary disease and/or alanine aminotransferase (ALT)
    >2 x upper limit of normal (ULN).
    High sensitivity C-reactive protein (hsCRP) > 2 x ULN.
    Hemoglobin <10 g/dL, white blood cell count (WBC) <3 x 10^9/L.
    Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen, anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab).
    Secondary OA.
    Ipsilateral hip OA.
    Symptomatic contralateral knee OA with WOMAC A1 pain subscore (walking pain) >30 on 100-mm VAS.
    History of osteonecrosis and/or rapidly progressive OA.
    Intra-articular injection within 3 months prior to inclusion.
    Unable to be maintained for at least 2 weeks prior to entry into study on paracetamol (No non-steroidal non-inflammatory drugs [NSAID] use during the 12 weeks of the study; after the end-of-study visit [Day 84 ±
    7] patients may be given a NSAID if necessary to provide better control of OA symptoms).
    Any Investigational Medicinal Product within 3 months prior to the study.

    ACT13830:
    Women of childbearing potential.
    Pregnant or breastfeeding women.
    Any uncontrolled, chronic condition or laboratory finding which, in the
    opinion of the Investigator, could potentially put the patient at increased
    risk.
    Patients with clinically significant or uncontrolled hepatic,
    gastrointestinal, cardiovascular, respiratory, neurological (including
    diabetic neuropathy), psychiatric, hematological, renal, or
    dermatological disease, or any other medical condition, such as
    symptomatic peripheral vascular disease of the study leg (prior or
    current), clinically significant venous or lymphatic stasis present in the
    study leg, that might interfere with the evaluation of investigational
    medicinal product (IMP) according to Investigator's medical judgment.
    Chondrocalcinosis.
    Fibromyalgia.
    Moderately severe or severe depression as indicated by Patient Health
    Questionnaire-9 (PHQ-9) total score at screening visit.
    Severe anxiety as indicated by Generalized Anxiety Disorder (GAD-7)
    score at screening visit.
    History or presence of drug or alcohol abuse (alcohol consumption >40
    grams per day)
    Any patient who, in the judgment of the Investigator, is likely to be
    noncompliant during the study, or unable to cooperate because of a
    language problem or poor mental development, or unable to use an
    electronic diary daily.
    Abnormal coagulation parameters: outside the range international normalized ratio (INR) 0.85-1.15, activated partial thromboplastin time
    >33 seconds, platelets <140 x 10^9/L.
    Moderate to severe renal impairment.
    Underlying hepatobiliary disease and/or alanine aminotransferase (ALT)
    >2 x upper limit of normal (ULN).
    High sensitivity C-reactive protein (hsCRP) >2 x ULN.
    Hemoglobin <10 g/dL, white blood cell count (WBC) <3 x 10^9/L.
    Positive result on any of the following tests: hepatitis B surface antigen
    (HBsAg), anti-hepatitis C virus (anti-HCV) antibodies, anti-human
    immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2
    Ab).
    Secondary OA.
    Ipsilateral hip OA.
    History of osteonecrosis and/or rapidly progressive OA (RPOA).
    Intraarticular injection within 3 months prior to inclusion.
    Unable to be maintained for at least 2 weeks prior to entry into study on
    paracetamol (no non-steroidal anti-inflammatory drug [NSAID] use
    during the 12 weeks of the study; after the end of study visit [Day 84 ±
    7] patients may be given an NSAID if necessary to provide better control
    of OA symptoms).
    Any IMP within 3 months prior to the study.
    Any knee MRI contraindication.
    Patients at risk of developing a RPOA with pre-existing findings on MRI
    of the target knee at baseline.
    Patients with painDETECT questionnaire (PD-Q) score > 18.
    E.5 End points
    E.5.1Primary end point(s)
    TDU13828
    1.Proportion of patients with adverse events;
    2.Proportion of patients with clinically significant changes in physical examination, vital signs and 12-lead electrocardiogram;
    3.Proportion of patients with clinically significant changes in laboratory tests including hematology, biochemistry and urinalysis.

    ACT13830:
    Change from baseline in weekly mean score of WOMAC A1 pain subscore (walking pain) collected daily in the target knee, as measured by the VAS 0-100
    E.5.1.1Timepoint(s) of evaluation of this end point
    TDU13828
    1.Up to Day 84 after single intra-articular dose of GZ389988A, followed by a safety follow-up period over 12 additional weeks (by phone calls)
    2. and 3.: Up to Day 84 after single intra-articular dose of GZ389988A

    ACT13830:
    Averaged over 4 weeks (up to Day 28)
    E.5.2Secondary end point(s)
    TDU13828:
    Assessment of pharmacokinetic parameters:
    1.Maximum plasma concentration (Cmax) of GZ389988A single dose
    intra-articular (IA)
    2.Area under the curve from time zero to last quantifiable concentration
    (AUClast) of single dose GZ389988A IA
    3.Area under curve (AUC) of single dose GZ389988A IA
    4.Plasma elimination half-life (t1/2z) of single dose GZ389988A IA
    5.Time to peak plasma concentration (tmax) of single dose GZ389988A
    IA
    dose GZ389988A IA
    7.Apparent volume of distribution (Vz/F) of single dose GZ389988A IA
    8.Apparent total body clearance(CL/F) of single dose GZ389998A IA
    9.Synovial fluid concentrations (if possible) of single dose GZ389988A
    IA
    10.Change from baseline in WOMAC index (total score)
    11.Change from baseline in WOMAC pain (including WOMAC A1 pain
    subscores)
    12.Change from baseline in WOMAC stiffness and physical function
    subscores

    ACT13830:

    1.Change from baseline in weekly mean score of WOMAC A1 pain
    subscore (walking pain) collected daily in the target knee, as measured
    by the VAS 0-100
    2.Change from baseline in weekly mean score of WOMAC A1 pain
    subscore collected daily in the target knee
    3.Change from baseline in weekly mean score of WOMAC A1 pain
    subscore collected daily in the target knee
    4.Change from baseline in weekly mean score of overall knee pain
    collected daily in the target knee
    5.Change from baseline in patient global assessment (PGA) of disease
    status
    6. Change from baseline in WOMAC index (total score for pain, stiffness,
    and physical function subscales), pain, stiffness and physical function
    subscores
    7. Patient Global Impression of Change (PGIC)
    8. Patient's global assessment of response to therapy (PGART)
    9. Rate of response to therapy according to OMERACT-OARSI
    10. WOMAC A1 responder rate based on percentage of patients with
    reduction in pain intensity of at least 30% and 50% at endpoint
    compared to baseline
    11. Time to first WOMAC A1 response for both ≥30% and 50%
    reductions in pain intensity
    12. Amount of rescue medication intake
    E.5.2.1Timepoint(s) of evaluation of this end point
    TDU13828:
    1.,2.,3.,4.,5.,6.,7.,8. : 24 timepoints up to Day 84
    9. 3 timepoints up to Day 84
    10., 11.,12. : over 1, 2, 3, 4, 6, 8, 10, and 12 weeks following the single
    intra-articular injection
    ACT13830:
    1. Averaged over 12 weeks (up to Day 84)
    2. Averaged over 1, 2, 3, 6, 8, and 10 weeks
    3. At 1,2,3,4,6,8,10 and 12 weeks.
    4. and 5. : At and averaged over 1, 2, 3, 4, 6, 8, 10, and 12 weeks
    6. Averaged over 1, 2, 3, 4, 6, 8, 10, and 12 weeks
    7. and 8. : over the last four weeks at Day 28 (1 to 4 weeks), Day 56 (5
    to 8 weeks), and Day 84 (9 to 12 weeks)
    9. By Day 28, Day 56, and Day 84
    10. Over 4 weeks (up to Day 28) and 12 weeks (up to Day 84) and at 1,
    2, 3, 4, 6, 8, 10, and 12 week
    11. At 1, 2, 3, 4, 6, 8, 10, 12 weeks
    12. Up to day 84
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    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 Yes
    E.8.1.7.1Other trial design description
    Ascending dose (TDU13828)
    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 trial2
    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.8.4.1Number of sites anticipated in Member State concerned1
    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 No
    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
    End of the trial after the 12-week safety follow-up by phone calls following the end-of-study visit
    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 months7
    E.8.9.1In the Member State concerned days17
    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: 92
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 52
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state144
    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 the end of the trial, the patients with painful osteoarthritis will be treated according to the standard of care in Germany, under the supervision of their medical practitioner.
    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 Decision2015-04-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-03-26
    P. End of Trial
    P.End of Trial StatusCompleted
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2019 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA