E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Myelofibrosis (MF) is classified as a myeloproliferative neoplasm (MPN) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028537 |
E.1.2 | Term | Myelofibrosis |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objectives of this study are to evaluate spleen response rate and symptom response rate of 2 dose regimens of imetelstat (9.4 mg/kg and 4.7 mg/kg imetelstat given intravenous [IV] every 3 weeks) in subjects with intermediate-2 or high-risk MF who are relapsed after or refractory to JAK inhibitor treatment. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: - To assess the safety of imetelstat - To assess CR or PR, CI, spleen response, symptoms response, and anemia response per modified 2013 IWG-MRT criteria, duration of responses, and overall survival (OS). - To evaluate the pharmacokinetics of imetelstat - To evaluate the PK/response and pharmacodynamic (PD) relationships with factors that include hemoglobin concentration, spleen size, and platelet count - To evaluate the immunogenicity of imetelstat - To assess the effect of treatment on PROs (patient-reported outcomes) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Diagnosis of PMF according to the revised WHO criteria; or PET-MF or PPV-MF according to the IWG-MRT criteria - DIPSS intermediate-2 or high risk MF - Measurable splenomegaly prior to study entry as demonstrated by palpable spleen measuring greater than or equal to (>=) 5 cm below the left costal margin OR spleen volume of >= 450 cm^3 measured by MRI - Active symptoms of MF as demonstrated by a symptom score of at least 5 points (on a 0 to 10 scale) on at least one of the symptoms or a score of 3 or greater on at least 2 of the symptoms - Documented progressive disease during or after JAK inhibitor therapy - ECOG performance status 0, 1 or 2 |
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E.4 | Principal exclusion criteria |
- Peripheral blood blast count of >= 10% or bone marrow blast count of >=10% - Prior treatment with imetelstat - Major surgery within 4 weeks prior to randomization - Active systemic hepatitis infection requiring treatment (carriers of hepatitis virus are permitted to enter the study), of any type or known acute or chronic liver disease including cirrhosis - Prior history of hematopoietic stem cell transplant |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Percentage of participants who Achieve Greater than or equal to 35 percent (%) Reduction in Spleen Volume at Week 24 (Spleen response rate is defined as the percentage of participants who achieve >= 35% reduction in spleen volume at Week 24 from baseline as measured by imaging scans.)
- Percentage of participants who Achieve Greater than or equal to 50 percent (%) Reduction in Total Symptom Score at Week 24 (Symptom response rate is defined as the percentage of participants who achieve >= 50% reduction in TSS at Week 24 from baseline as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) version 2.0 diary.) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Complete remission (CR) or partial remission (PR) per modified 2013 IWG-MRT criteria - Clinical improvement (CI) per modified 2013 IWG-MRT criteria - Number of Participants with Responses per 2013 IWG-MRT (Spleen response, symptoms response, and anemia response per modified 2013 IWG-MRT will be assessed.) - Duration of Treatment Response and Remission (Duration of spleen response, duration of symptoms response, duration of CR or PR, duration of CI, and duration of anemia response will be reported.) - Overall Survival (Overall survival is defined as the time from randomization to date of death from any cause.) - European Organization for Research and treatment of Cancer (EORTC) QLQ-C30 Score - EuroQol-EQ-5D (EQ-5D-5L) Health Questionnaire Score - Brief Pain Inventory- Short Form (BPI) Score - Patient’s Global Impression of Change (PGIC) - Number of Participants with Adverse Events (AEs) - Maximum Plasma Concentration (Cmax) of Imetelstat (The Cmax is the maximum observed plasma concentration.) - Time to Reach Maximum Concentration (tmax) of Imetelstat (The tmax is time to reach the maximum observed plasma concentration.) - Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC [0-24h]) of Imetelstat (AUC 0-24h is area under the plasma concentration-time curve from time 0 to 24 hours postdose.) - Elimination Half-Life (t [1/2] Lambda) of Imetelstat (Elimination half-life (t [1/2] Lambda) is associated with the terminal slope (lambda [z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z).) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity Biomarker Patient Reported Outcome |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 48 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
France |
Germany |
Israel |
Italy |
Korea, Republic of |
Spain |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial 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
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The end of the main study is defined as 18 months after the last subject is enrolled or when the sponsor terminates the study, whichever comes first. The Extension Phase will end approximately 2 year after the clinical cutoff for the final analysis of the main study, or when the sponsor terminates the study, whichever occurs first. The full study will end at that time. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 9 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 9 |