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    The EU Clinical Trials Register currently displays   43881   clinical trials with a EudraCT protocol, of which   7295   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).

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    Summary
    EudraCT Number:2020-005106-25
    Sponsor's Protocol Code Number:D8241C00001
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2021-10-05
    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 ConcernedGermany - BfArM
    A.2EudraCT number2020-005106-25
    A.3Full title of the trial
    A Modular Phase I/II, Open-Label, Multi-Centre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AZD0466 Monotherapy or in Combination in Patients with Advanced Haematological Malignancies
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Assess the Safety, Tolerability, Pharmacokinetics of AZD0466 in Patients with Advanced Haematological Malignancies
    A.3.2Name or abbreviated title of the trial where available
    NIMBLE
    A.4.1Sponsor's protocol code numberD8241C00001
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04865419
    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 SponsorAstraZeneca AB
    B.1.3.4CountrySweden
    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 supportAstraZeneca AB
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstraZeneca AB
    B.5.2Functional name of contact pointInformation Center
    B.5.3 Address:
    B.5.3.1Street Addressnot applicable
    B.5.3.2Town/ citynot applicable
    B.5.3.3Post codenot applicable
    B.5.3.4CountryUnited States
    B.5.6E-mailinformation.center@astrazeneca.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 nameAZD0466 powder for concentrate for solution for infusion
    D.3.2Product code AZD0466
    D.3.4Pharmaceutical form Powder and solvent 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 INNAZD0466
    D.3.9.2Current sponsor codeAZD0466
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Advanced Haematological Malignancies
    E.1.1.1Medical condition in easily understood language
    Blood cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10007051
    E.1.2Term Cancer (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
    To assess the safety and tolerability of AZD0466 in patients with advanced haematological malignancies
    E.2.2Secondary objectives of the trial
    To characterize the pharmacokinetic (PK) profile of AZD0466 following intravenous administration (via PK profiles of the active moiety AZD4320 in plasma) [Core Module]
    To estimate the preliminary antitumor activity of AZD0466 [Module 1]
    To assess the drug-drug interaction potential between AZD0466 and the azole antifungal
    voriconazole [Module 2]
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Subjects must be aged ≥18 years inclusive, at the time of signing the informed consent. In some countries parental consent may be required in addition to an assent form for patients who are 18 years of age.
    • Histologically confirmed acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL) or intermediate or higher risk myelodysplastic syndrome (MDS; Part A only) for which there are limited treatment options known to provide clinical benefit.
    • Subjects must have received at least one prior line of therapy, and an established standard of care with proven benefit, and for which the patient is eligible, must not be available at the time of enrolment.
    • Eastern Cooperative Oncology Group performance status ≤2. Performance status must not have deteriorated by ≥2 levels within 2 weeks after providing informed consent.
    • Predicted life expectancy ≥8 weeks.
    • White blood cell count must be <10 x 10^9/L prior to the first dose in Cycle 1, Day 1. Treatment with hydroxyurea (AML) or high-dose steroids (ALL and leukaemia of ambiguous lineage) during screening and Cycle 1 to control white blood cell count is permitted.
    • Adequate organ function at screening as per the protocol defined criteria.
    • Adequate cardiac function as demonstrated by LVEF > 50% on screening cardiac multigated acquisition, magnetic resonance image or echocardiogram.
    • Willing and able to participate in all required study evaluations and procedures including receiving IV administration of study treatment and admission to the hospital, when required, for administration of study treatment and monitoring.
    • For inclusion in the genetic component of the study, patients must fulfil protocol defined criteria.
    • Women of childbearing potential and men should use protocol defined contraceptive measures.
    E.4Principal exclusion criteria
    • Unresolved toxicity from prior anticancer therapy of Common Terminology Criteria for Adverse Events Grade ≥2. Patients with Grade 2 neuropathy or Grade 2 alopecia are eligible.
    • Active idiopathic thrombocytopenic purpura.
    • Haemopoietic Stem cell transplant < 100 days prior to the first dose of study treatment.
    • Immunosuppression for graft versus host disease (GVHD) or GVHD prophylaxis within 4 weeks prior to the first dose of study treatment. The following are permitted: (a) topical steroids for GVHD; (b) systemic steroids for GVHD up to 2 weeks prior to the first dose of study treatment; (c) treatment with high-dose steroids (ALL and leukaemia of ambiguous lineage) for white blood cell count control is permitted during screening, and in Cycle 1 up to 4 days.
    • Active central nervous system (CNS) leukaemia/leptomeningeal disease/spinal cord compression. Patients who have a history of CNS leukaemia must be free of CNS leukaemia for >30 days prior to the first dose of study treatment, and the most recent 2 lumbar punctures must be negative for leukaemic cells, to be eligible.
    • Known uncontrolled infection with cytomegalovirus.
    • Active infection including human immunodeficiency virus, Hepatitis B, Hepatitis C, or severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).
    • As judged by the Investigator: any evidence of severe or uncontrolled systemic diseases; current unstable or uncompensated respiratory or cardiac conditions; uncontrolled hypertension; history of, or active, bleeding diatheses (eg, haemophilia or von Willebrand disease); uncontrolled active systemic fungal, bacterial, or other infection.
    • Any of the given cardiac criteria: subjects with history of myocarditis within one year of study entry, or heart failure New York Heart Association Functional Classification Class 3 or 4; mean resting corrected QT interval (QTcF) ≥470 msec obtained from 3 electrocardiograms (ECGs), in the absence of a cardiac pacemaker; abnormalities in rhythm, conduction or morphology of resting ECG; any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age.
    • History of another life-threatening malignancy ≤2 years prior to first dose of study treatment. The following are permitted: myelodysplastic syndrome or myeloproliferative neoplasm (including chronic myelomonocytic leukaemia); malignancy treated with curative intent and with no evidence of active disease present; adequately treated lentigo malignant melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer; adequately treated carcinoma in situ without current evidence of disease.
    • Any of the mentioned procedures or conditions currently or in the 6 months prior to the first dose of study treatment: coronary artery bypass graft; angioplasty; vascular stent; myocardial infarction; angina pectoris; haemorrhagic or thrombotic stroke, including transient ischaemic attacks or any other CNS bleeding.
    • Treatment with any of the mentioned therapy: radiotherapy less than
    3 weeks prior to first study treatment; anticancer agents within ≤14
    days or 5 half-lives prior to the first dose of study treatment; Treatment
    with high-dose steroids (ALL and leukaemia of ambiguous lineage) for
    white blood cell count control is permitted during screening, and in Cycle
    1 up to 4 days; subjects can continue to receive hydroxyurea (AML) until the start of Cycle 2, and should be stopped once the white blood cell count falls <10 × 10^9/L; immunotherapies and cellular therapies within 4 weeks prior to the first dose of study treatment; investigational drugs within ≤14 days or 5 half-lives prior to the first dose of study treatment; major surgery ≤21 days, or minor surgical procedures ≤7 days, prior to the first dose of study treatment; prescription or non-prescription drugs or other products i.e., sensitive substrates of BCRP, OCT2, OAT3, OATP1B1, OATP1B3, CYP2B6, CYP2C8, CYP2C9 or CYP2D6, reversible CYP3A inhibitors, and medications with known risk of Torsades de Pointe which cannot be discontinued within 5-half-lives prior to the first dose of study treatment and withheld throughout the study until 14 days after the last dose of AZD0466; moderate or strong mechanism-based inhibitors or inducers of CYP3A4 which cannot be discontinued within 14 days prior to the first dose of study treatment, and withheld until 14 days after the last dose of AZD0466; concurrent anti-coagulation therapy, including aspirin and heparin, which cannot be stopped.
    • History of hypersensitivity to polyethylene glycol (PEG), PEGylated products or drugs with a similar chemical structure or class to AZD0466 or other BH3 mimetic.
    E.5 End points
    E.5.1Primary end point(s)
    • Number of subjects with adverse events (AEs) and serious adverse events (SAEs) [Core Module]
    • Changes from baseline in laboratory findings, physical examinations, performance status, electrocardiograms and vital signs [Core Module]
    • Dose-limiting toxicity [Module 1]
    • Maximum tolerated dose [Module 1]
    • Recommended Phase II dose [Module 1]
    E.5.1.1Timepoint(s) of evaluation of this end point
    • Module 1 and Module 2: From Screening until post treatment follow-up (28 days after last dose)
    • Module 1: From Screening until post treatment follow-up (28 days after last dose); Module 2: From Screening until Day 19
    • Day 1 to Day 35 of Cycle 1 (35-day Cycle)
    • Day 1 to Day 35 of Cycle 1 (35-day Cycle)
    • Day 1 to Day 35 of Cycle 1 (35-day Cycle)
    E.5.2Secondary end point(s)
    • Plasma concentrations and derived PK parameters for total and released AZD4320
    • Complete Response Rate (CR+CRi); Time to Response (TTR); Duration of Response (DoR); Overall Survival (OS) [Module 1]
    • Area under the plasma concentration-curve (AUC) of AZD4320 after administration of AZD0466 alone and in combination with voriconazole [Module 2]; Maximum observed plasma (peak) drug concentration (Cmax) of AZD4320 after administration of AZD0466 alone and in combination with voriconazole [Module 2]
    E.5.2.1Timepoint(s) of evaluation of this end point
    • Module 1: Days 1 and 4, and days 8, 9, 10, 11 of Cycle 1; Module 2: Days 1, 2, 3, 4, and 8 (Period 1) and days 15, 16, 17, 18, 19 (Period 3) during Cycle 1 (21 days)
    • Module 1: Day 1 until post treatment follow-up (28 days after last dose)
    • Module 2: Days 1, 2, 3, 4, and 8 (Period 1) and days 15, 16, 17, 18, 19 (Period 3) during Cycle 1 (21 days)
    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 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) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy
    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 No
    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 No
    E.8.2.4Number of treatment arms in the trial2
    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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA16
    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
    Korea, Republic of
    United States
    France
    Germany
    Italy
    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 the study is defined as the date of the last visit of the last subject in the study or last scheduled procedure shown in the Schedule of Activity for the last subject in the study globally.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months6
    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: 68
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 100
    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 state19
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 45
    F.4.2.2In the whole clinical trial 168
    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)
    Not Applicable
    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 Decision2021-11-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-11-15
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2023-07-24
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