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    Summary
    EudraCT Number:2014-001617-12
    Sponsor's Protocol Code Number:AP24534-14-203
    National Competent Authority:Portugal - INFARMED
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2016-03-03
    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 ConcernedPortugal - INFARMED
    A.2EudraCT number2014-001617-12
    A.3Full title of the trial
    A Randomized, Open-label, Phase 2 Trial of Ponatinib in Patients with Resistant Chronic Phase Chronic Myeloid Leukemia to Characterize the Efficacy and Safety of a Range of Doses
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of Iclusig (ponatinib), an oral kinase-inhibitor treatment
    administered, by standard dose or reduced doses, for patients with
    Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML)
    who no longer benefit from, or who have an abnormal gene (T315I
    positive) marker for resistance to other kinase-inhibitor treatments.
    A.3.2Name or abbreviated title of the trial where available
    OPTIC
    A.4.1Sponsor's protocol code numberAP24534-14-203
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02467270
    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 SponsorARIAD Pharmaceuticals, Inc. (a wholly-owned subsidiary of Takeda Pharmaceutical Company Limited)
    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 supportARIAD Pharmaceuticals, Inc. (a wholly-owned subsidiary of Takeda Pharmaceutical Company Limited)
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationARIAD Pharmaceuticals, Inc. (a wholly-owned subsidiary of Takeda Pharmaceutical Company Limited)
    B.5.2Functional name of contact pointDrug Information Call Center
    B.5.3 Address:
    B.5.3.1Street Address40 Landsdowne Street
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeMA 02139
    B.5.3.4CountryUnited States
    B.5.4Telephone number15107402412
    B.5.5Fax number18008816092
    B.5.6E-mailmedical@mlnm.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 Yes
    D.2.5.1Orphan drug designation numberEU/3/09/716 - treatment of CML
    D.3 Description of the IMP
    D.3.1Product nameponatinib
    D.3.2Product code AP24534
    D.3.4Pharmaceutical form Film-coated 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 INNPonatinib
    D.3.9.1CAS number 943319-70-8
    D.3.9.2Current sponsor codeAP24534
    D.3.9.3Other descriptive namePonatinib hydrochloride
    D.3.9.4EV Substance CodeSUB91901
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 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.2.1.1.1Trade name Iclusig
    D.2.1.1.2Name of the Marketing Authorisation holderARIAD Pharma Ltd.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/09/716 - treatment of CML
    D.3 Description of the IMP
    D.3.1Product nameponatinib
    D.3.2Product code AP24534
    D.3.4Pharmaceutical form Film-coated 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 INNPonatinib
    D.3.9.1CAS number 943319-70-8
    D.3.9.2Current sponsor codeAP24534
    D.3.9.3Other descriptive namePonatinib hydrochloride
    D.3.9.4EV Substance CodeSUB91901
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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: 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.2.1.1.1Trade name Iclusig
    D.2.1.1.2Name of the Marketing Authorisation holderARIAD Pharma Ltd.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/09/716 - treatment of CML
    D.3 Description of the IMP
    D.3.1Product nameponatinib
    D.3.2Product code AP24534
    D.3.4Pharmaceutical form Film-coated 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 INNPonatinib
    D.3.9.1CAS number 943319-70-8
    D.3.9.2Current sponsor codeAP24534
    D.3.9.3Other descriptive namePonatinib hydrochloride
    D.3.9.4EV Substance CodeSUB91901
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number15
    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: 4
    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.2.1.1.1Trade name Iclusig
    D.2.1.1.2Name of the Marketing Authorisation holderARIAD Pharma Ltd.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/09/716 - treatment of CML
    D.3 Description of the IMP
    D.3.1Product nameponatinib
    D.3.2Product code AP24534
    D.3.4Pharmaceutical form Film-coated 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 INNPonatinib
    D.3.9.1CAS number 943319-70-8
    D.3.9.2Current sponsor codeAP24534
    D.3.9.3Other descriptive namePonatinib hydrochloride
    D.3.9.4EV Substance CodeSUB91901
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number45
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Chronic Phase Chronic Myeloid Leukemia
    E.1.1.1Medical condition in easily understood language
    Chronic Phase Chronic Myeloid Leukemia
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10054352
    E.1.2Term Chronic phase chronic myeloid leukemia
    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
    To characterize the efficacy of ponatinib administered in 3 starting doses
    (45 mg, 30 mg, and 15 mg daily) in patients with CP-CML who are
    resistant to prior TKI therapy or have T315I mutation, as measured by
    ≤ 1% BCR-ABL1IS at 12 months.
    E.2.2Secondary objectives of the trial
    •To characterize the rate of major molecular response (MMR) at 12 and 24 months and rate of major cytogenetic response (MCyR) by 12 months
    •To evaluate duration of MMR
    •To characterize the rates of AOEs, VTEs, AEs, and serious AEs (SAEs)
    •To evaluate safety differences among the 3 starting dose cohorts,particularly for AOEs and VTEs
    •To collect sparse PK samples to contribute to population PK and exposure-response analyses of safety and efficacy
    •To characterize the rates of cytogenetic responses and molecular responses; durability will be assessed by evaluating ≤ 1% BCR-ABL1IS response and major molecular response (MMR) at and by 6, 12, 18, and 24 months
    •To characterize the rate of discontinuation, dose reductions, and interruptions
    •To characterize the rates of hematologic responses
    •To evaluate time to response, duration of response, and survival outcomes
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    All patients must meet all of the following inclusion criteria for study entry:
    1. Have CP-CML and have received at least two prior TKI therapies and have demonstrated resistance to treatment OR Have documented history of presence of T315I mutation after receiving
    any number of prior TKI.
    a. The diagnosis of CML will be made using standard hematopathologic and cytogenetic criteria; CP-CML will be defined by all of the following:
    i. < 15% blasts in bone marrow
    ii. < 30% blasts plus promyelocytes in bone marrow
    iii. < 20% basophils in peripheral blood
    iv. ≥ 100 × 109/L platelets (≥ 100,000/mm3)
    v. No evidence of extramedullary disease except hepatosplenomegaly
    vi. No prior diagnosis of AP- or BP-CML
    b. Cytogenetic assessment at screening must demonstrate the BCR-ABL1 fusion by presence of the t(9;22) Philadelphia chromosome
    i. Variant translocations are only allowed provided they meet inclusion criteria 1d
    c. Resistance to prior TKI therapy is defined as follows (patients must
    meet at least 1 criterion):
    i. Three months after the initiation of prior TKI therapy: No cytogenetic response (> 95% Ph+) or failure to achieve CHR or new mutation
    ii. Six months after the initiation of prior TKI therapy: BCR-ABL1IS
    >10% and/or Ph+ >65% or new mutation
    iii. Twelve months after the initiation of prior TKI therapy: BCR-ABL1IS
    >10% and/or Ph+ >35% or new mutation.
    iv. At any time after the initiation of prior TKI therapy, the development of a new BCR-ABL1 kinase domain mutation(s).
    v. At any time after the initiation of prior TKI therapy, the development of new clonal evolution
    vi. At any time after the initiation of prior TKI therapy, the loss of CHR, or CCyR, or the confirmed loss of MMR in 2 consecutive tests, one of which has a BCR-ABL1IS transcript level of ≥1% or new mutation
    d. > 1% of BCR-ABL1IS as shown by real-time polymerase chain reaction
    2. Age ≥ 18 years old.
    3. Have an Eastern Cooperative Oncology Group (ECOG) performance
    status of 0, 1, or 2.
    4. Have adequate renal function as defined by the following criterion:
    a. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) for institution
    b. Estimated creatinine clearance ≥ 30 mL/min (Cockcroft-Gault
    formula)
    5. Have adequate hepatic function as defined by the following criteria:
    a. Total serum bilirubin ≤ 1.5 × ULN, unless due to Gilbert's syndrome
    b. Alanine aminotransferase (ALT) ≤ 2.5 × ULN, or ≤ 5 × ULN if leukemic infiltration of the liver is present
    c. Aspartate aminotransferase (AST) ≤ 2.5 × ULN, or ≤ 5 × ULN if
    leukemic infiltration of the liver is present
    6. Have normal pancreatic status as defined by the following criterion:
    a. Serum lipase and amylase ≤ 1.5 × ULN
    7. Have normal QT interval corrected (Frederica) (QTcF) interval on
    screening electrocardiogram (ECG) evaluation, defined as QTcF of ≤ 450 ms in males or ≤ 470 ms in females.
    8. Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential).
    9. Agree to use a highly effective form of contraception with sexual
    partners from randomization through at least 4 months after the end of treatment (for female and male patients who are fertile).
    10. Provide written informed consent.
    11. Be willing and able to comply with scheduled visits and study
    procedures.
    12. Have recovered from toxicities related to prior anticancer therapy to NCI CTCAE v 4.0 grade ≤1.
    E.4Principal exclusion criteria
    Patients are not eligible for participation in the study if they meet any of the following exclusion criteria:
    1. Have used any approved TKIs or investigational agents within 2
    weeks or 6 half-lives of the agent, whichever is longer, prior to receiving study drug.
    2. Received interferon, cytarabine or immunotherapy within 14 days; or any other cytotoxic chemotherapy, radiotherapy, or investigational
    therapy within 28 days prior to receiving the first dose of ponatinib, or have not recovered (> grade 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE], v4.0) from AEs (except alopecia) due to agents previously administered.
    3. Have undergone autologous or allogeneic stem cell transplant (SCT) < 60 days prior to receiving the first dose of ponatinib; have any evidence of ongoing graft versus-host disease (GVHD) or GVHD requiring immunosuppressive therapy.
    4. Are being considered for hematopoietic SCT (HSCT) within 6-12
    months of enrollment (note: ponatinib is not to be used as a bridge to HSCT in this trial).
    5. Are taking medications with a known risk of Torsades de Pointes.
    6. Have previously been treated with ponatinib.
    7. Have active central nervous system (CNS) disease as evidenced by
    cytology or pathology; in the absence of clinical CNS disease, lumbar
    puncture is not required. History itself of CNS involvement is not
    exclusionary if CNS has been cleared with a documented negative
    lumbar puncture.
    8. Have clinically significant, uncontrolled, or active cardiovascular
    disease, specifically including, but not restricted to:
    a. Any history of myocardial infarction (MI), unstable angina,
    cerebrovascular accident, or transient ischemic attack (TIA)
    b. Any history of peripheral vascular infarction, including visceral
    infarction
    c. Any revascularization procedure, including the placement of a stent
    d. Congestive heart failure (CHF) (New York Heart Association [NYHA]
    class III or IV) within 6 months prior to enrollment, or left ventricular
    ejection fraction (LVEF) less than lower limit of normal, per local
    institutional standards, within 6 months prior to enrollment
    e. History of clinically significant (as determined by the treating
    physician) atrial arrhythmia or any history of ventricular arrhythmia
    f. Venous thromboembolism, including deep venous thrombosis or
    pulmonary embolism, within 6 months prior to enrollment
    9. Have uncontrolled hypertension (i.e., >150 and >90 for SBP and DBP, respectively). Patients with hypertension should be under treatment at study entry to ensure blood pressure control. Those requiring 3 or more antihypertensive medications should be discussed with the medical monitor.
    10. Have poorly controlled diabetes defined as HbA1c values of > 7.5%. Patients with preexisting, well-controlled, diabetes are not excluded.
    11. Have a significant bleeding disorder unrelated to CML.
    12. Have a history of alcohol abuse.
    13. Have a history of either acute pancreatitis within 1 year of study
    enrollment or of chronic pancreatitis.
    14. Have malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of study drug.
    15. Have a history of another malignancy, other than cervical cancer in situ or basal cell or squamous cell carcinoma of the skin; the exception is if patients have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy.
    16. Are pregnant or lactating.
    17. Have undergone major surgery (with the exception of minor surgical procedures, such as catheter placement or BM biopsy) within 14 days prior to the first dose of ponatinib.
    18. Have an active infection which requires intravenous antibiotics.
    19. Have a known history of human immunodeficiency virus infection; testing is not required in the absence of prior documentation or known history.
    20. Have any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of the drug.
    21. Have hypersensitivity to the ponatinib active substance or to any of its inactive ingredients listed in Section 14.7.1 of the protocol.
    E.5 End points
    E.5.1Primary end point(s)
    ≤ 1% BCR-ABL1IS
    E.5.1.1Timepoint(s) of evaluation of this end point
    At 12 months for each starting dose cohort.
    E.5.2Secondary end point(s)
    •Molecular response rates: MMR at 12 and 24 months
    •Cytogenetic response rates: MCyR by 12 months
    •Duration of MMR
    •Safety
    a.Rate of AOEs and VTEs in each dose cohort
    b.Rate of AEs in each dose cohort
    c.Rate of SAEs in each dose cohort
    •Cytogenetic response rates: CCyR at 12 months
    •Molecular response rates: MR4, and MR4.5 by and at 3-month intervals and MR1 (≤ 10% BCR-ABL1IS) at 3 months
    •Hematologic response rate: Complete hematologic response (CHR) at 3 months
    •Tolerability:
    a.Rate of discontinuation due to AEs in each dose cohort
    b.Dose reductions due to AE in each dose cohort
    c.Dose interruptions in each dose cohort
    •Duration of response:
    a.Rate of ≤1% BCR-ABL1IS by 12 months and at and by 6, 18, and 24
    months
    b.MMR at and by 6 and 18 months; and by 12 and 24 months
    •Duration of response in responders
    •Time to response
    •Rate of progression to accelerated phase (AP-) or blast phase (BP-) CML
    •Progression Free Survival (PFS)
    •Overall Survival (OS)
    E.5.2.1Timepoint(s) of evaluation of this end point
    At each visit and the final analysis will be done at the end of the study.
    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 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) 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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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 No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    This is a controlled study of ponatinib at three different starting doses.
    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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA49
    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
    Argentina
    Australia
    Belgium
    Canada
    Chile
    Czech Republic
    Denmark
    Finland
    France
    Germany
    Hong Kong
    Italy
    Japan
    Korea, Republic of
    Netherlands
    Norway
    Poland
    Portugal
    Russian Federation
    Singapore
    Spain
    Sweden
    Taiwan
    United Kingdom
    United States
    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 years5
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months1
    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: 202
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 74
    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 Yes
    F.3.3.7.1Details of other specific vulnerable populations
    Patients with incurable diseases
    F.4 Planned number of subjects to be included
    F.4.1In the member state13
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 150
    F.4.2.2In the whole clinical trial 276
    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
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2016-03-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-05-30
    P. End of Trial
    P.End of Trial StatusOngoing
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