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    Summary
    EudraCT Number:2015-002874-19
    Sponsor's Protocol Code Number:63935937MDS3001
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2015-11-03
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2015-002874-19
    A.3Full title of the trial
    A Study to Evaluate Imetelstat (GRN163L) in Transfusion-Dependent Subjects with IPSS Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) that is Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study to Evaluate Imetelstat (GRN163L) in Subjects with IPSS Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS).
    A.4.1Sponsor's protocol code number63935937MDS3001
    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 SponsorGeron Corporation
    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 supportGeron Corporation
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGeron Corporation
    B.5.2Functional name of contact pointClinical Trial Enquiries
    B.5.3 Address:
    B.5.3.1Street Address919 E. Hillsdale Blvd.
    B.5.3.2Town/ cityFoster City, CA
    B.5.3.3Post code94404
    B.5.3.4CountryUnited States
    B.5.6E-mailmds3001-info@Geron.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/3/15/1593
    D.3 Description of the IMP
    D.3.1Product nameImetelstat sodium
    D.3.2Product code GRN163L
    D.3.4Pharmaceutical form Lyophilisate 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 INNImetelstat sodium
    D.3.9.1CAS number 1007380-31-5
    D.3.9.2Current sponsor codeGRN163L
    D.3.9.3Other descriptive nameIMETELSTAT SODIUM
    D.3.9.4EV Substance CodeSUB174121
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number210
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboLyophilisate for solution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Myelodysplastic syndrome (MDS)
    E.1.1.1Medical condition in easily understood language
    Myelodysplastic syndrome (MDS)
    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 HLT
    E.1.2Classification code 10028536
    E.1.2Term Myelodysplastic syndromes
    E.1.2System Organ Class 100000004851
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Part 1: To evaluate the efficacy and safety of imetelstat in transfusion dependent subjects with low or intermediate-1 risk MDS that is relapsed/refractory to ESA treatment.

    Part 2: To compare the efficacy, in terms of RBC TI, of imetelstat to placebo in transfusion dependent subjects with low or intermediate-1 risk MDS that is relapsed/refractory to ESA treatment.

    Extension Phase: To evaluate the long-term safety, overall survival (OS), and disease progression, including progression to acute myeloid leukemia (AML) in transfusion dependent subjects with low or
    immediate-1 risk to MDS that is relapsed/refractory to ESA treatment receiving imetelstat.
    E.2.2Secondary objectives of the trial
    For Part 1 and Part 2:
    - To assess the safety of imetelstat in subjects with MDS
    - To assess the time to RBC TI and duration of RBC TI
    - To assess the rate of hematologic improvement
    - To assess the rates of CR, PR or marrow complete remission (mCR)
    - To assess OS
    - To assess progression free survival (PFS)
    - To assess time to progression to AML
    - To assess the rate and amount of supportive care, including transfusions and myeloid growth factors (Part 2 only)
    - To evaluate the pharmacokinetics and immunogenicity of imetelstat in subjects with MDS
    - To assess the effect of imetelstat treatment on patient reported outcomes (PROs)
    - To assess the effect of treatment on medical resource utilization (Part 2 only)
    - To assess the effect of imetelstat on corrected QT (QTc) interval in subjects in the Ventricular Repolarization substudy (to be reported separately from Part 2 )
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Protocol Amendment 7 dated 2 September 2021_ Attachment 11: Ventricular Repolarization (QTc) Substudy.
    Study Objectives:To evaluate the effect of imetelstat on ventricular repolarization in approximately 45 subjects:
    The primary objective of this substudy is to determine the relationship between the plasma concentrations of imetelstat and QTc interval changes.
    The secondary objectives of this substudy are as follows:
    -To investigate the effect of imetelstat on the following ECG parameters: heart rate, PR, QRS, and T-Wave morphology by using baseline adjusted ECGs on study drug versus placebo.
    -To evaluate the pharmacokinetics of imetelstat.

    Safety and limited efficacy will be assessed as per the Time and Events Schedule as listed in Table 12 of Protocol. At the time of the primary analysis of this substudy, all safety data from the main study will be provided along with data specific to this set of subjects. In particular, any cardiac-related adverse events will be summarized in both the main study and substudy populations. The Data Monitoring Committee will review all substudy events on an ongoing basis.
    E.3Principal inclusion criteria
    1. Man or woman ≥18 years of age (or the legal age of consent in the jurisdiction the study is taking place);
    2. Criterion modified per Amendment 1.
    2.1. Criterion modified per Amendment 2.
    2.2. Criterion modified per Amendment 3
    2. 3 In Part 1, diagnosis of MDS according to WHO criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to C1D1. A local laboratory report from this diagnostic bone marrow aspirate and biopsy must be reviewed and approved by the sponsor (Attachment 1). In Part 2, diagnosis of MDS according to WHO criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to Randomization (Attachment 1). A sample of the baseline bone marrow aspirate and biopsy must be submitted to the Independent Central Pathology Reviewer for diagnostic confirmation. Central laboratory review is required to confirm diagnosis prior to Randomization.
    3. IPSS low or intermediate-1 risk MDS (Attachment 3);
    4. Criterion modified per Amendment 1.
    4.1. RBC transfusion dependent, defined as requiring at least 4 RBC units transfused over an 8-week period during the 16 weeks prior to C1D1 (Part 1) or Randomization (Part 2) (defined in Section 3.1); pre-transfusion Hb should be ≤9.0 g/dL to count towards the 4 units total;
    5. Has MDS that is relapsed/refractory to ESA treatment; as defined by meeting any one of the criteria below:
    5.1. Received at least 8 weeks of treatment with a minimum weekly dose of epoetin alfa 40,000 U, epoetin beta 30,000 U or darbepoetin alfa 150 mcg (or equivalent agent/dose), without having achieved a Hb rise ≥1.5 g/dL or decreased RBC transfusion requirement by at least 4 units over 8 weeks
    5.2.1 Transfusion dependence or reduction in Hb by ≥1.5 g/dL after hematologic improvement from at least 8 weeks of treatment with therapies outlined in inclusion criteria 5.1, in the absence of another explanation.
    5.4. Endogenous serum EPO level >500 mU/mL;
    ....
    More details see protocol
    E.4Principal exclusion criteria
    1. Subject has known allergies, hypersensitivity, or intolerance to imetelstat or its excipients (refer to the IB );
    2.1 Subject has received an experimental or investigational drug or used an invasive investigational medical device within 30 days prior to C1D1 (Part 1) or Randomization (Part 2) (defined in Section 3.1) or is currently enrolled in an investigational study;
    3. Prior treatment with imetelstat;
    4. Criterion modified per Amendment 2. 4.1 Have received corticosteroids >30 mg/day prednisone or equivalent, or growth factor treatment within 4 weeks prior to C1D1 (Part 1) or Randomization (Part 2);
    5. Criterion modified per Amendment 2. 5.1 Prior treatment with a hypomethylating agent (eg, azacitidine, decitabine);
    5.2 Criterion 5.2 replaced by criterion 5.2.1 per Amendment 5.
    5.2.1 Prior treatment with lenalidomide, thalidomide, or other thalidomide analogues;
    5.3 Criterion 5.3 replaced by criterion 5.3.1 per Amendment 5.
    5.3.1 Has received an ESA or any anti-MDS therapy, chemotherapy, immunomodulatory, or immunosuppressive therapy within 4 weeks prior to C1D1 (Part 1) or Randomization (Part 2) (8 weeks for long-acting ESAs);
    6. Prior history of hematopoietic stem cell transplant;
    7. Anemia attributed to factors other than MDS (including hemolysis, chronic renal failure, hepatitis, gastrointestinal bleeding);
    8. Major surgery within 4 weeks prior to C1D1 (Part 1) or Randomization (Part 2)(excluding the placement of vascular access and other minor surgical procedures);
    9. Diagnosed or treated for malignancy other than MDS, except:
    9.1. Malignancy treated with curative intent and with no known active disease present for ≥3 years before C1D1 (Part 1) or Randomization (Part 2)
    9.2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
    9.3. Adequately treated cervical carcinoma in situ without evidence of disease;
    10. Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of C1D1 (Part 1) or Randomization (Part 2), or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification;
    ...
    More details see protocol
    E.5 End points
    E.5.1Primary end point(s)
    Percentage of participants without any red blood cell (RBC) transfusion during any consecutive 8 week period.
    E.5.1.1Timepoint(s) of evaluation of this end point
    8 weeks
    E.5.2Secondary end point(s)
    1. - Safety of imetelstat in subjects with MDS (eg, incidence, intensity, and type of adverse events, vital signs measurements, clinical laboratory values, ECGs changes, and deaths);
    2. - 24-week RBC TI rate, defined as the proportion of subjects without any RBC transfusion during any consecutive 24 weeks (168 days) starting from Study Day 1;
    3. - Time to the 8-week RBC TI, defined as the interval from Study Day 1 to the first day of the first 8-week RBC TI period;
    4. - Duration of RBC TI, defined as the first day of the first 8-week RBC TI period to the date of the first RBC transfusion after the TI period;
    5. - Rate of hematologic improvement, including HI-E, per IWG 2006;
    6. OS, defined as the interval from Study Day 1 to death from any cause. Survival time of living subjects will be censored on the last date a subject is known to be alive or lost to follow-up;
    7. Progression free survival, defined as the time interval from Study Day 1 to the first date of disease progression or death from any cause, whichever occurs first. For subjects who do not have documented disease progression and who are still alive at the end of the study or clinical cutoff will be censored at the last disease evaluation date.
    8. Time to progression to AML, defined as the interval from Study Day 1 to the date of AML diagnosis. For subjects who have not progressed to AML and are still alive at the cutoff date for the analysis or who withdraw from the study (withdrawal of consent or lost to follow-up), data will be censored at the date of the last disease evaluation;
    9. Amount and relative change in RBC transfusions;
    10. Rate of myeloid growth factors usage, defined as the proportion of subjects receive any myeloid growth factors starting from Study Day 1; duration of myeloid growth factor administered starting from Study Day 1;
    11. Assessment of QUALMS, FACT-An, and EQ-5D-5L;
    12. Pharmacokinetic parameters (eg, Cmax, AUC0-t), and immunogenicity of imetelstat (eg, antibodies to imetelstat);
    13. Medical resource utilization data including hospitalization, emergency room visits, and hematology specialist visits;
    14. ECG parameters including change in QT interval by Fridericia's correction method (ΔQTcF) in the Ventricular Repolarization substudy (Part 2 only).
    E.5.2.1Timepoint(s) of evaluation of this end point
    1/ up to follow-up (30 days posttreatment [approximately 2 years])
    2-5/ up to 2 years after enrollment of the last participant
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Immunogenicity
    Biomarker
    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) Yes
    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 No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    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 Yes
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA68
    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
    Canada
    Israel
    Korea, Republic of
    United States
    Switzerland
    Russian Federation
    Turkey
    Ukraine
    Belgium
    Czechia
    France
    Germany
    Italy
    Netherlands
    Poland
    Spain
    United Kingdom
    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
    The End of the Study is defined as 2 years after Study Entry of the last subject in the main study of Part 2 or anytime the sponsor terminates the study, whichever comes first.
    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 months4
    E.8.9.1In the Member State concerned days28
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days22
    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: 50
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 120
    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 state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 110
    F.4.2.2In the whole clinical trial 170
    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)
    The sponsor will ensure that subjects benefiting from treatment with imetelstat will be able to continue treatment after the End of the Study.
    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 Decision2015-11-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-11-11
    P. End of Trial
    P.End of Trial StatusOngoing
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