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    Summary
    EudraCT Number:2018-001594-24
    Sponsor's Protocol Code Number:CABL001E2201
    National Competent Authority:Austria - BASG
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2018-07-24
    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 ConcernedAustria - BASG
    A.2EudraCT number2018-001594-24
    A.3Full title of the trial
    A phase 2, multi-center, open-label, randomized study of oral asciminib added to imatinib versus continued imatinib versus switch to nilotinib in patients with CML-CP who have been previously treated with imatinib and have not achieved deep molecular response
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of efficacy and safety of asciminib in addition to imatinib in CML-CP patients without a deep level or response on imatinib
    A.4.1Sponsor's protocol code numberCABL001E2201
    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 SponsorNovartis Pharma AG
    B.1.3.4CountrySwitzerland
    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 supportNovartis Pharma AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNovartis Pharma GmbH
    B.5.2Functional name of contact pointDrug Regulatory Affairs
    B.5.3 Address:
    B.5.3.1Street AddressJakov-Lind-Straße 5 / Top 3.05
    B.5.3.2Town/ cityVienna
    B.5.3.3Post code1020
    B.5.3.4CountryAustria
    B.5.4Telephone number +43 1 86657 0
    B.5.5Fax number +43 1 86657 6458
    B.5.6E-mailaustria.dra@novartis.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 ABL001
    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 INNASCIMINIB
    D.3.9.2Current sponsor codeABL001
    D.3.9.4EV Substance CodeSUB188597
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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 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 ABL001
    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 INNASCIMINIB
    D.3.9.2Current sponsor codeABL001
    D.3.9.4EV Substance CodeSUB188597
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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.IMP: 3
    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 Glivec
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Limited
    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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameGlivec
    D.3.2Product code STI571
    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 INNimatinib
    D.3.9.1CAS number 152459-95-5
    D.3.9.2Current sponsor codeSTI571
    D.3.9.3Other descriptive nameIMATINIB
    D.3.9.4EV Substance CodeSUB25387
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number400
    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 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 Glivec
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Limited
    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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameGlivec
    D.3.2Product code STI571
    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 INNimatinib
    D.3.9.1CAS number 152459-95-5
    D.3.9.2Current sponsor codeSTI571
    D.3.9.3Other descriptive nameIMATINIB
    D.3.9.4EV Substance CodeSUB25387
    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 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: 5
    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 Tasigna
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Limited
    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/3/06/375
    D.3 Description of the IMP
    D.3.1Product nameTasigna
    D.3.2Product code AMN107
    D.3.4Pharmaceutical form Capsule, hard
    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 INNNILOTINIB
    D.3.9.1CAS number 641571-10-0
    D.3.9.2Current sponsor codeAMN107
    D.3.9.4EV Substance CodeSUB25225
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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: 6
    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 Tasigna
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Limited
    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/3/06/375
    D.3 Description of the IMP
    D.3.1Product nameTasigna
    D.3.2Product code AMN107
    D.3.4Pharmaceutical form Capsule, hard
    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 INNNILOTINIB
    D.3.9.1CAS number 641571-10-0
    D.3.9.2Current sponsor codeAMN107
    D.3.9.4EV Substance CodeSUB25225
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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 Myelogenous Leukemia in chronic phase (CML-CP), previously treated with imatinib and have not achieved deep molecular response
    E.1.1.1Medical condition in easily understood language
    Chronic Myelogenous Leukemia is a cancer of the blood characterized by a gene mutation (Philadelphia chromosome) which causes proliferation of white blood cells in the bone marrow
    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 10009012
    E.1.2Term Chronic myelogenous 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 assess whether asciminib 40 mg QD + imatinib or asciminib 60 mg QD + imatinib is more effective than continued imatinib
    E.2.2Secondary objectives of the trial
    • - To estimate efficacy of switch to nilotinib
    - To estimate difference in efficacy between asciminib 60 mg + imatinib and switch to nilotinib
    - To estimate difference in efficacy between asciminib 40 mg + imatinib and switch to nilotinib
    • To assess additional parameters of the efficacy of
    - asciminib 60 mg added to imatinib vs continued imatinib or switch to nilotinib
    - asciminib 40 mg added to imatinib vs continued imatinib or switch to nilotinib
    • To characterize the safety and tolerability profile of asciminib 60 mg or 40 mg + imatinib vs continued imatinib or switch to nilotinib
    • To assess the pharmacokinetic profile of asciminib 60 mg or 40 mg and imatinib when administered in combination
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects eligible for inclusion in this study must meet all of the following
    criteria:
    1. Signed informed consent must be obtained prior to participation in the
    study.
    2. Male or female patients ≥ 18 years of age with a confirmed diagnosis
    of CML-CP defined as:
    • < 15% blasts in peripheral blood and bone marrow
    • < 30% blasts plus promyelocytes in peripheral blood and bone marrow
    -< 20% basophils in the peripheral blood
    • ≥ 100 x 109/L (≥ 100 000/mm3) platelets
    • No evidence of extramedullary leukemic involvement, with the
    exception of hepatosplenomegaly
    3. Minimum of one year (12 calendar months) treatment with imatinib
    first line for CML-CP (patients have to be on imatinib 400 mg QD at
    randomization and had no dose change in the past three months).
    4. BCR-ABL1 levels > 0.01% IS and ≤ 1% IS at the time of
    randomisation as confirmed with a central assessment at screening;
    patients must not have achieved deep molecular response (MR4 IS)
    confirmed by 2 consecutive tests at any time during prior imatinib
    treatment. An isolated, single test result with BCR-ABL1 levels < 0.01 %
    (MR4 IS) is allowed, however it should not have been observed within
    the 9 months prior to randomization .
    5. Patient must meet the following laboratory values before
    randomization:
    • Absolute Neutrophil Count ≥ 1.5 x 109/L
    • Platelets ≥ 75 x 109/L
    • Hemoglobin (Hgb) ≥ 9 g/dL
    • Serum creatinine < 1.5 mg/dL
    • Total bilirubin ≤ 1.5 x ULN except for patients with Gilbert's syndrome
    who may only be included with total bilirubin ≤ 3.0 x ULN
    • Aspartate transaminase (AST) ≤ 3.0 x ULN
    • Alanine transaminase (ALT) ≤ 3.0 x ULN
    • Alkaline phosphatase ≤ 2.5 x ULN
    • Serum lipase ≤ 1.5 x ULN. For serum lipase > ULN - ≤ 1.5 x ULN, value
    must be considered not clinically significant and not associated with risk
    factors for acute pancreatitis
    6. Patients must have the following laboratory values (≥ LLN) or
    corrected to within normal limits with supplements prior to
    randomization:
    - Potassium (potassium increase of up to 6.0 mmol/L is acceptable if
    associated with creatinine clearance* within normal limits)
    - Total calcium (corrected for serum albumin); (calcium increase of up to
    12.5 mg/dl or 3.1 mmol/L is acceptable if associated with creatinine
    clearance* within normal limits)
    - Magnesium (magnesium increase of up to 3.0 mg/dL or 1.23 mmol/L if
    associated with creatinine clearance* within normal limits)
    *Creatinine clearance as calculated using Cockcroft-Gault formula
    E.4Principal exclusion criteria
    Subjects meeting any of the following criteria are not eligible for
    inclusion in this study.
    1. Treatment failure according to European Leukemia Network criteria
    (Baccarani et al 2013) during imatinib treatment.
    • after 3 months of treatment no Complete Hematologic Response (CHR)
    and/or Ph+ > 95%
    • after 6 months of treatment BCR-ABL1 > 10% and/or Ph+ > 35%
    • after 12 months of treatment BCR-ABL1 > 1% and/or Ph+ > 0
    • at any time loss of CHR, loss of CCyR, confirmed loss of MMR*,
    mutations, clonal chromosomal abnormalities in Ph+ cells (CCA/Ph+)
    *In 2 consecutive tests, of which one with a BCR-ABL level ≥1%.
    2. Known second chronic phase of CML after previous progression to
    AP/BC.
    3. Previous treatment with any TKIs other than imatinib.
    4. History or current diagnosis of ECG abnormalities indicating
    significant risk or safety for subjects participating in the study such as:
    • History of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to randomization
    • Concomitant clinically significant arrhythmias, e.g. sustained
    ventricular tachycardia, and clinically significant second or third degree
    AV block without a pacemaker
    • Resting QTcF ≥ 450 msec (male) or ≥ 460 msec (female) prior to
    randomization
    • Long QT syndrome, family history of idiopathic sudden death or
    congenital long QT syndrome, or any of the following:
    • Risk factors for Torsades de Pointes including uncorrected
    hypokalemia or hypomagnesemia, history of cardiac failure, or history of
    clinically significant/symptomatic bradycardia
    • Concomitant medications with a "known" risk of Torsades de Pointes
    per crediblemeds.org that cannot be discontinued or replaced by safe
    alternative medication
    • inability to determine the QTcF interval
    5. Severe and/or uncontrolled concurrent medical disease that in the
    opinion of the investigator could cause unacceptable safety risks or
    compromise compliance with the protocol (e.g. uncontrolled diabetes,
    active or uncontrolled infection, uncontrolled clinically significant
    hyperlipidemia and high serum amylase).
    6. History of acute pancreatitis within 1 year prior to randomization or
    past medical history of chronic pancreatitis.
    7. History of chronic liver disease or ongoing acute liver disease.
    8. History of other active malignancy within 3 years prior to
    randomization with the exception of basal cell skin cancer, indolent
    prostate cancer and carcinoma in situ treated curatively.
    9. Known history of Human Immunodeficiency Virus (HIV), chronic
    Hepatitis B (HBV), or chronic Hepatitis C (HCV) infection. Testing for
    Hepatitis B surface antigen (HBsAg) and Hepatitis B core antibody (anti-
    HBc) will be performed at study entry. If HBsAg or anti-HBc is positive,
    Hepatitis B surface antibody (anti-HBs) and/or HBVDNA measurement is
    recommended to confirm negative viral status.
    10. Impairment of gastrointestinal (GI) function or GI disease that may
    significantly alter the absorption of study drug (e.g. ulcerative disease,
    uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small
    bowel resection, or gastric bypass surgery).
    11. Treatment with strong inducers or inhibitors of CYP3A that cannot be
    discontinued or switched to a different medication at least one week
    prior to the start of treatment and for the duration of the study.
    12. Patients must avoid consumption of grapefruit, Seville oranges or
    products containing the juice of each during the entire study and
    preferably 7 days before the first dose of study medications, due to
    potential CYP3A4 interaction with the study medications. Orange juice is
    allowed.
    13. History of hypersensitivity to any of the study treatments or its
    excipients or to drugs of similar chemical classes.
    14. Participation in a prior investigational study within 30 days prior to
    randomization or within 5 half-lives of the investigational product,
    whichever is longer.
    15. Pregnant or nursing (lactating) women.
    Women of child-bearing potential, defined as all women physiologically
    capable of becoming pregnant, unless they are using highly effective
    methods of contraception while taking study treatment and for 14 days
    after stopping study medication. Highly effective contraception methods
    include: - see more details in section 5.2 of the protocol.
    16. Patients who have achieved deep molecular response (MR4 IS),
    confirmed by 2 consecutive tests at any time during prior imatinib
    treatment.
    E.5 End points
    E.5.1Primary end point(s)
    • Molecular Response (MR)4.5 rate at 48 weeks
    E.5.1.1Timepoint(s) of evaluation of this end point
    48 weeks
    E.5.2Secondary end point(s)
    • - Molecular Response (MR)4.5 rate at 48 weeks
    - Difference in rate of MR4.5 at 48 weeks
    • - Rate of MR4.5 at 96 weeks
    - Rate of MR4.5 by 48 and 96 weeks
    - Sustained MR4.5 at 96 weeks
    - Time to MR4.5
    • Incidence and severity of adverse events, changes in laboratory values, clinically notable ECG abnormalities and vital signs
    • Plasma concentrations of asciminib and imatinib when administered in combination. PK parameters include but are not limited to Cmax, Tmax, Cmin, AUClast and AUCtau
    E.5.2.1Timepoint(s) of evaluation of this end point
    The assessments are done for each parameter according to visits indicated in the Visit Schedule. For more details please refer to Visit Evaluation Schedule table 8-1 and 8-2 of the protocol
    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 No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) 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 Yes
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial4
    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 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
    Australia
    Austria
    Canada
    Chile
    Czechia
    Denmark
    France
    Germany
    Hong Kong
    Italy
    Japan
    Korea, Republic of
    Poland
    Portugal
    Russian Federation
    Spain
    Taiwan
    United Kingdom
    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
    Study completion is defined as 96 weeks after the last randomized subject received the first dose of treatment + 30 days for the safety Follow up, or ... for further details see section 9.2 of the protocol.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    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: 72
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 8
    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 state4
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 50
    F.4.2.2In the whole clinical trial 80
    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)
    At the time of the study completion, subjects eligible for TFR may enter a separate TFR study. For subjects who do not enter a separate TFR study and in the opinion of the investigator are continuing to benefit from the study drug(s), efforts will be made to continue providing the study treatment outside the study. Options include, but are not limited to, a post-trial access program or access to commercial supplies in applicable countries.
    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 Decision2018-10-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-10-17
    P. End of Trial
    P.End of Trial StatusOngoing
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