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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:2018-003739-32
    Sponsor's Protocol Code Number:1801
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2019-10-30
    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 number2018-003739-32
    A.3Full title of the trial
    Actuate 1801: Phase 1/2 Study of 9-ING-41, a Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor, as a Single Agent and Combined with Chemotherapy, in Patients with Refractory Hematological Malignancies or Solid Tumors.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical trial of a new drug known as 9-ING-41, that will take place in
    patients with tumors or cancers that affect the blood and lymph system.
    9-ING-41 will be assessed as a standalone drug as well as being assessed
    when taken with chemotherapy drugs
    A.3.2Name or abbreviated title of the trial where available
    Actuate 1801: Phase 1/2 of 9-ING-41 in Refractory Malignancies
    A.4.1Sponsor's protocol code number1801
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03678883
    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 SponsorActuate Therapeutics Inc
    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 supportActuate Therapeutics Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationActuate Therapeutics Inc
    B.5.2Functional name of contact pointClinical Operations
    B.5.3 Address:
    B.5.3.1Street Address1751 River Run, Suite 400
    B.5.3.2Town/ cityFort Worth, Texas,
    B.5.3.3Post code76107
    B.5.3.4CountryUnited States
    B.5.6E-mailclinops@actuatetherapeutics.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 name9-ING-41
    D.3.4Pharmaceutical form 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 INN9-ING-41
    D.3.9.1CAS number 1034895-42-5
    D.3.9.3Other descriptive name3-(5-fluorobenzofuran-3-yl)-4-(5-methyl-5H-[1,3]dioxolo[4,5 f]indol-7-yl)-1H-pyrrole-2,5-dione
    D.3.9.4EV Substance CodeSUB197944
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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.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
    Refractory Hematologic Malignancies or Solid Tumors
    E.1.1.1Medical condition in easily understood language
    Advanced Cancers
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10066476
    E.1.2Term Haematological malignancy
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10065147
    E.1.2Term Malignant solid tumor
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Parts 1 and 2: To evaluate the safety and tolerability, describe any dose-limiting toxicity (DLT), determine the maximum tolerated dose (MTD) or highest protocol-defined doses (in the absence of exceeding the MTD) and the recommended Phase 2 study dose (RP2D) for 9-ING-41 as monotherapy (Study Part 1) and in combination with chemotherapies (Study Part 2) in patients with relapsed or refractory malignancies.
    Part 3: To assess clinical benefit in patients with relapsed or refractory malignancies treated with 9-ING-41-based combinations at the RP2D established in Part 2.
    To assess clinical benefit in patients with relapsed or refractory
    malignancies treated with 9-ING-41-based combinations at the RP2D established in Part 2.
    E.2.2Secondary objectives of the trial
    1. To assess pharmacokinetics and pharmacodynamics of 9-ING-41
    2. To correlate response rates with specific molecular tumor profile(s) in a descriptive fashion
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Is able to understand and voluntarily sign a written informed consent and is willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures.
    2. Is aged ≥ 18 years
    3. Has pathologically confirmed advanced or metastatic malignancy characterized by one or more of the following:
    a. Patient is intolerant of existing therapy(ies) known to provide clinical benefit for their condition
    b. Malignancy is refractory to existing therapy(ies) known to potentially provide clinical benefit
    c. Malignancy has relapsed after standard therapy
    d. Malignancy for which there is no standard therapy that improves survival by at least 3 months
    4. Has evaluable tumor(s) by standard radiological and/or laboratory assessments as applicable to their malignancy – in Part 3, patients with solid tumors must have at least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) v1.1 criteria, measured preferably by computed tomography (CT) scan or magnetic resonance
    image (MRI). In Part 3, patients with glioblastoma multiforme (GBM) or other central nervous system (CNS) tumors, the tumor must be measurable, defined as a clearly enhancing tumor with at least two perpendicular diameters at entry equal or superior to 1cm. Patients with GBM will have progression after chemoradiotherapy with or without antiangiogenic treatment at least 3 months after the end of radiotherapy. Radiotherapy at a dose of no more than 65 Gy with stereotactic radiosurgery or brachytherapy is allowable if recurrence was histologically proven.
    5. Has laboratory function within specified parameters (may be
    repeated):
    a. Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 500/mL; hemoglobin ≥ 8.5 g/dL, platelets ≥ 50,000/mL
    b. Adequate liver function: transaminases (aspartate
    aminotransferase/alanine aminotransferase, AST/ALT) and alkaline phosphatase ≤ 3 (≤ 10X the upper limit of normal (ULN) in the setting of liver metastasis or infiltration with malignant cells) x ULN; bilirubin ≤ 1.5 x ULN
    c. Adequate renal function: creatinine clearance ≥ 60 mL/min (Cockcroft and Gault)
    d. Adequate blood coagulation: international normalized ratio (INR) ≤2.3
    e. Serum amylase and lipase ≤ 1.5 x ULN
    6. Has adequate performance status (PS): Eastern Co-operative
    Oncology Group (ECOG) PS 0-2
    7. Has received the final dose of any of the following treatments/procedures with the specified minimum intervals before first dose of study drug (unless in the opinion of the investigator and the study medical coordinator the treatments/ procedures will not compromise patient safety or interfere with study conduct:
    • Chemotherapy, immunotherapy, or systemic radiation therapy - 14 days or ≥ 5 half-lives (whichever is shorter)
    • Focal radiation therapy – 7 days
    • Systemic and topical corticosteroids – 7 days
    • Surgery with general anesthesia – 7 days
    • Surgery with local anesthesia – 3 days
    8. May continue endocrine therapies (e.g. for breast or prostate cancer) and/or anti-human epidermal growth factor (Her2) therapies while on this study
    9.Women of childbearing potential must have a negative baseline blood or urine pregnancy test within 72 hours of first study therapy. Women may be neither breastfeeding nor intending to become pregnant during study participation and must agree to use effective contraceptive methods (hormonal or barrier method of birth control, or true abstinence) for the duration of study participation and in the following 90 days after discontinuation of study treatment
    10. Male patients with partners of childbearing potential must take appropriate precautions to avoid fathering a child from screening until 90 days after discontinuation of study treatment and use appropriate barrier contraception or true abstinence
    11. Must not be receiving any other investigational medicinal product
    12. For study Parts 2 and 3, must have received prior therapy for the same malignancy including the same potential partner agent(s) as that/those being considered for administration on study in combination with 9-ING-41
    E.4Principal exclusion criteria
    1. Is pregnant or lactating
    2. Is known to be hypersensitive to any of the components of 9-ING-41 or to the excipients used in its formulation
    3. Has not recovered from clinically significant toxicities as a result of prior anticancer therapy, except alopecia and infertility. Recovery is defined as
    ≤ Grade 1 severity per Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 (v 4.03)
    4. Has significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, or stroke within 6 months of the first dose of 9-ING-41, or cardiac arrhythmia requiring medical treatment detected at screening
    5. Has had a myocardial infarction within 12 weeks of the first dose of 9-ING-41 or has electrocardiogram (ECG) abnormalities that are deemed medically relevant by the investigator or study medical coordinator
    6. Has symptomatic rapidly progressive brain metastases or leptomeningeal involvement as assessed by CT scan or MRI. Patients with stable brain metastases or leptomeningeal disease or slowly progressive disease are eligible provided that they have not required new treatments for this disease in a 28-day period before the first dose of study drug, and anticonvulsants and steroids are at a stable dose for a period of 14 days prior to the first dose of study drug
    7. Has had major surgery (not including placement of central lines) within 7 days prior to study entry or is planned to have major surgery during the course of the study (major surgery may be defined as any invasive operative procedure in which an extensive resection is performed, e.g. a body cavity is entered, organs are removed, or normal anatomy is altered. In general, if a mesenchymal barrier is opened (pleural cavity, peritoneum, meninges), the surgery is considered major)
    8. Has any medical and/or social condition which, in the opinion of the investigator or study medical coordinator would preclude study participation
    9. Has received an investigational anti-cancer drug in the 14-day period before the first dose of study drug (or within 5 half-lives if longer) or is currently participating in another interventional clinical trial
    10. Has a current malignancy other than the target cancer
    11. Is considered to be a member of a vulnerable population (for example, prisoners)
    E.5 End points
    E.5.1Primary end point(s)
    The efficacy endpoints are the following:
    • Objective response rate (ORR), defined as the percent of patients with Complete Response (CR) or Partial Response (PR) according to RECIST 1.1 criteria or other standard malignancy-specific response criteria, relative to the efficacy population.
    • Duration of Response (DoR), defined as the time from documentation of tumor response to disease progression
    • Progression-Free Survival (PFS), defined as the time from study enrolment until objective tumor progression or death
    • Overall survival (OS), defined as the time from study entry to death from any cause

    Adverse events will be monitored during the period starting on the date of receipt of first administration of 9-ING-41 and ending 30 days after the final administration of 9 ING-41. All patients who receive any dose (any amount) of 9-ING-41 or combination regimen will be included in the summaries and listings of safety data. Overall safety profile and tolerability will be characterized by type, frequency, severity, timing, duration and relationship of study drug to adverse events and laboratory abnormalities.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Efficacy/response endpoints will be evaluated as per study assessment defined in the protocol (Section 3.5 Assessments During Study)

    Safety will be monitored during the period starting on the date of first dose of investigational product and ending 30 days +/- 5 days after the final administration of 9 ING-41.
    E.5.2Secondary end point(s)
    Specific secondary end points for patients with GBM or other CNS malignancies will include progression free survival, land­mark analyses for progression free and overall survival, response rates according to the Response Assessment in Neuro­Oncology (RANO) criteria, neurologic deterioration–free survival (defined as the time from study entry to documentation of neurologic deterioration or death), clinical or neurologic deterioration–free survival, glucocorticoid use, the development of symptoms of neurocognitive deterioration, and assessments of predictive factors.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Defined as the time from study entry to documentation of neurologic deterioration or death
    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 No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled 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 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.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA14
    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
    Denmark
    Germany
    Netherlands
    Spain
    United Kingdom
    United States
    France
    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 years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    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: 100
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 70
    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 state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 170
    F.4.2.2In the whole clinical trial 350
    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)
    Patients should have a documented EOT visit. Safety follow up should be performed within 28 days of the last dose of 9-ING-41 (+/- 5 days). Survival follow-up for a 12 month period following study last therapy should be reported, where feasible.
    Quarterly visits are requested inclusive of monitoring according to the protocol or standard of care for patients with refectory cancers (i.e as per standard on-going monitoring on the study) for all patients for a year after last dose of 9-ING-41.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Developmental Therapeutics Consortium
    G.4.3.4Network Country United Kingdom
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-10-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-02-28
    P. End of Trial
    P.End of Trial StatusCompleted
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu Apr 25 03:19:52 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA