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   36821   clinical trials with a EudraCT protocol, of which   6079   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:2016-003328-22
    Sponsor's Protocol Code Number:56022473MDS2002
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2016-12-22
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2016-003328-22
    A.3Full title of the trial
    A Phase 2 Proof-of-Concept Study to Separately Evaluate the Activity of Talacotuzumab
    (JNJ-56022473) or Daratumumab in Transfusion-Dependent Subjects with Low or
    Intermediate-1 Risk Myelodysplastic Syndromes (MDS) who are Relapsed or Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Proof-of Concept Study to Separately Study Talacotuzumab or Daratumumab in Low-Risk Intermediate-1 Risk Myelodysplastic Syndromes (MDS) patients
    A.4.1Sponsor's protocol code number56022473MDS2002
    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 SponsorJanssen-Cilag International NV
    B.1.3.4CountryBelgium
    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 supportJanssen Research & Development, LLC
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationJanssen-Cilag International NV
    B.5.2Functional name of contact pointClinical Registry Group
    B.5.3 Address:
    B.5.3.1Street AddressArchimedesweg 29
    B.5.3.2Town/ cityLeiden
    B.5.3.3Post code2333 CM
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+31 71 524 21 66
    B.5.5Fax number+31 71 524 21 10
    B.5.6E-mailClinicalTrialsEU@its.jnj.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 nameTalacotuzumab
    D.3.2Product code JNJ-56022473
    D.3.4Pharmaceutical form Powder for concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTalacotuzumab
    D.3.9.2Current sponsor codeJNJ-56022473
    D.3.9.4EV Substance CodeSUB176319
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 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 nameDaratumumab
    D.3.2Product code Hu-Max-CD38
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDARATUMUMAB
    D.3.9.1CAS number 945721-28-8
    D.3.9.2Current sponsor codeJNJ-54767414 (Daratumumab)
    D.3.9.3Other descriptive nameHUMAX-CD38
    D.3.9.4EV Substance CodeSUB175772
    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 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 typehuman monoclonal antibody
    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
    Transfusion-Dependent Subjects with Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) who are Relapsed or Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment
    E.1.1.1Medical condition in easily understood language
    Myelodysplastic Syndromes (MDS)
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10028534
    E.1.2Term Myelodysplastic syndrome NOS
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the study is to evaluate the efficacy (transfusion independence [TI]) of talacotuzumab (JNJ-56022473) or daratumumab in transfusion-dependent subjects with low or intermediate-1 risk MDS whose disease has relapsed during treatment with or is refractory to ESAs.
    E.2.2Secondary objectives of the trial
    - To evaluate the safety of talacotuzumab or daratumumab in the study population
    - To evaluate the clinical benefit of talacotuzumab and daratumumab in this study population through:
    - Time to TI and duration of TI
    - Rate of HI, CR, and PR
    - Overall survival (OS)
    - Progression to AML
    - Rate and amount of supportive care, including transfusions and myeloid growth factors
    - To characterize the PK of talacotuzumab and daratumumab in the study population
    - To evaluate the immunogenicity of talacotuzumab and daratumumab in subjects with MDS
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. 18 years of age
    2. MDS according to World Health Organization criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to first dose. A local laboratory report from this diagnostic bone marrow aspirate and biopsy must be approved by the sponsor.
    3. IPSS low risk or intermediate-1 risk MDS
    4. RBC transfusion dependent
    - Received at least 4 units of RBCs over any 8 consecutive weeks during the 16 weeks prior to randomization-Pretransfusion Hb must have been ≤9.0 g/dL
    Source documentation for transfusions verified by the sponsor.
    5. Relapsed/refractory to ESA treatment; the sponsor must verify this diagnosis as defined by meeting any of the criteria below:
    - Received at least 8 weeks of treatment with a minimum weekly dose of epoetin alfa 40,000 U, epoetin beta 30,000 U or darbepoetin alfa 150 mcg (or equivalent
    agent/dose) without having achieved a Hb rise ≥1.5 g/dL or decreased RBC
    transfusion requirement by at least 4 units over 8 weeks
    - Transfusion dependence or reduction in Hb by ≥1.5 g/dL after hematologic
    improvement, in the absence of another explanation;
    - Endogenous serum EPO level >500 mU/mL
    Source documentation for failure of ESA treatment verified by the sponsor
    6. Adequate iron stores, defined as transferrin saturation greater than 20% and serum ferritin greater than 400 ng/mL, measured within the screening period, or adequate iron stores as demonstrated by recent (within 12 weeks prior to first dose) bone marrow examination with iron stain.
    7. ECOG performance status 0, 1 or 2
    8. Hematology laboratory test values within the following limits:
    - ANC ≥1.0 x 10 to the 9th/L (ie, ≥1,000/mm3) independent of growth factor support. For the screening ANC to be considered growth factor independent, a 7-day period after stopping the growth factor should be observed, or 7 half-lives of growth factor used, whichever is longer.
    - Platelets ≥50 x 10 to the 9th/L independent of platelet transfusion support. For the screening platelets to be considered independent of platelet transfusion support, platelet count must be stable for 3-4 days after the transfusion.
    9. Biochemical laboratory test values must be within the following limits:
    - Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤2.5 times
    the upper limit of normal (x ULN)
    - Creatinine clearance >40 mL/min
    - Total bilirubin ≤3.0 x ULN, except for subjects with Gilbert syndrome
    10. Women of childbearing potential and men who are sexually active must be practicing highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) during and after the study. Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for subject participating in clinical studies. Men must agree to not father a child or donate sperm during and after the study. Women must agree not to donate eggs (ova, oocytes) for the purpose of assisted reproduction. For females and males, these restrictions apply for at least 3 months after the last dose of study drug.
    11. A woman of childbearing potential must have a negative highly sensitive serum
    (B-human chorionic gonadotropin [B-hCG]) or urine pregnancy test at Screening.
    12. Each subject (or their legally acceptable representative) must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study. Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
    E.4Principal exclusion criteria
    1. Known allergies, hypersensitivity, or intolerance to talacotuzumab and daratumumab or their excipients
    2. Received any chemotherapy, immunomodulatory or immunosuppressive therapy, corticosteroids (>30 mg/day prednisone or equivalent) within 28 days prior to randomization
    3. Received other treatments for MDS within 28 days prior to first dose (eg, azacitidine, decitabine, lenalidomide, ESA (8 weeks for long-acting ESAs)
    4. History of hematopoietic stem cell transplant
    5. Del (5q) karyotype unless treatment with lenalidomide has failed. Failure is defined as either:
    1) having received at least 3 months of lenalidomide treatment without RBC
    transfusion benefit (IWG 2006);
    2) progression or relapse after hematologic improvement with lenalidomide (IWG 2006);
    3) discontinuation of lenalidomide due to toxicity; or
    4) unable to receive lenalidomide due to a contraindication. Source documentation for lenalidomide treatment failure must be verified by the sponsor.
    6. Anemia attributed to factors other than MDS (including hemolysis, chronic renal failure, hepatitis, gastrointestinal bleeding)
    7. Major surgery within 4 weeks prior to first dose (excludes the placement of a vascular access device and other minor surgical procedures)
    8. Active malignancy other than MDS ≤3 years before first dose, except:
    - Adequately treated non-melanoma skin cancer or lentigo maligna without current evidence of disease
    - Adequately treated cervical carcinoma in situ without current evidence of disease
    9. Clinically significant cardiovascular disease including:
    - myocardial infarction within 6 months of screening
    - unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, cardiac disease meeting New York Heart Association
    Class 3-4 definition)
    - uncontrolled or symptomatic cardiac arrhythmias
    - screening 12-lead ECG showing a baseline corrected QT interval (QTc) >470 msec
    10. Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal
    11. Known moderate or severe persistent asthma within the past 2 years or uncontrolled asthma of any classification. Note that subjects who currently have
    controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study.
    12. Uncontrolled active systemic infection requiring IV antibiotics
    13. Known history of human immunodeficiency virus (HIV) infection
    14. Active systemic hepatitis infection requiring treatment or other clinically active liver disease
    15. Females who are pregnant or are breastfeeding
    16. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator’s opinion, could compromise the subject’s safety, or put the study outcomes at undue risk. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is 8-week RBC TI, defined as absence of RBC transfusion during any consecutive 56 days (8 weeks) post randomization.
    E.5.1.1Timepoint(s) of evaluation of this end point
    6 months after the last subject is randomized
    E.5.2Secondary end point(s)
    1.) Transfusion independence lasting 168 days (24 weeks)
    2.) Time to TI
    3.) Duration of TI
    4.) Transfusions and myeloid growth factors usage
    5.) HI (including HI-E, HI-P, HI-N), CR, PR and cytogenetic response per IWG 2006
    6.) Overall survival
    7.) Progression to AML
    E.5.2.1Timepoint(s) of evaluation of this end point
    1.) 6 months after the last subject is randomized
    2.) 6 months after the last subject is randomized
    3.) 6 months after the last subject is randomized
    4.) 6 months after the last subject is randomized
    5.) 6 months after the last subject is randomized
    6.) 12 months after the last subject is randomized
    7.) 12 months after the last subject is randomized
    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 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 No
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    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 No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    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 concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA24
    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
    Belgium
    Italy
    Netherlands
    Russian Federation
    Spain
    United States
    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 end of study is defined as 1 year after the last subject is randomized or anytime the sponsor terminates the study.
    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 months7
    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 months7
    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: 15
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 45
    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 state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 40
    F.4.2.2In the whole clinical trial 60
    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)
    Subjects who are continuing to derive benefit from treatment as assessed by their investigator will continue to receive treatment and be monitored for safety by the sponsor.
    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 Decision2016-12-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-02-16
    P. End of Trial
    P.End of Trial StatusOngoing
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA