E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
subjects with either polycythemia vera (PV) or essential thrombocythemia (ET) |
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E.1.1.1 | Medical condition in easily understood language |
Blood disorder that means the body produces too many mature blood cells too quickly |
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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 | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036057 |
E.1.2 | Term | Polycythaemia vera |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10015493 |
E.1.2 | Term | Essential thrombocythaemia |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to determine the efficacy of MMB in subjects with PV or ET |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to determine the safety of MMB in subjects with PV or ET |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 years old
2.Diagnosis of either PV or ET as defined by the 2008 WHO Diagnostic Criteria
3.Requires treatment for PV or ET, in the opinion of the study investigator
4.Intolerant of, resistant to, or refuses current or available treatment for PV or ET
5.Direct bilirubin ≤ 2.0 x upper limit of normal (ULN)
6.AST (SGOT) and ALT (SGPT) ≤ 3X ULN
7.Calculated creatinine clearance (CrCl) of ≥ 45 mL/min
8.Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
9.Life expectancy > 24 weeks
10.Negative serum pregnancy test for female subjects (unless surgically sterile or greater than two years postmenopausal)
11.Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
12.Females who are nursing must agree to discontinue nursing before the first dose of IP
13.Able to comprehend and willing to sign informed consent form (ICF)
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E.4 | Principal exclusion criteria |
1.Prior splenectomy
2.Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection (subjects receiving outpatient antibacterial and/or antiviral treatments for infection that is under control or as infection prophylaxis may be included in the study), active or chronic bleeding event within 4 weeks prior to first dose of IP, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements as judged by treating physician
3.History of a concurrent or second malignancy except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to randomization, adequately treated Stage 1 or 2 cancer currently in complete remission (CR), or any other cancer that has been in CR for ≥ 5 years.
4.Major surgery within 28 days of first dose of IP
5.Known positive status for human immunodeficiency virus (HIV)
6.Chronic active or acute viral hepatitis A, B, or C infection (testing required for hepatitis B and C), or hepatitis B or C carrier
7.Myeloproliferative neoplasm-directed therapy, other than aspirin, hydroxyurea, anagrelide, and/or phlebotomy, within 21 days prior to the first dose of IP
8.Anagrelide within 7 days prior to the first dose of IP
9.Unresolved non-hematologic toxicities from prior therapies that are > CTCAE Grade 1
10.Presence of peripheral neuropathy ≥ Grade 2
11.Incomplete recovery from any surgery performed within 4 weeks prior to the first dose of IP
12.Unwilling or unable to take oral medication
13.Prior use of a JAK1 or JAK2 inhibitor
14.Use of strong CYP3A4 inducers within 1 week prior to the first dose of IP
15.Known hypersensitivity to the study investigational medicinal products, the metabolites, or formulation excipients
16. QTc interval > 450msec, unless attributed to bundle branch block |
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E.5 End points |
E.5.1 | Primary end point(s) |
the primary endpoint is defined by the ORR.
In the PV Cohort, the ORR is defined as the proportion of subjects with hematocrit < 45% in the absence of phlebotomy, WBC < 10 x 10^9/L, platelet count ≤ 400 x 10^9/L and resolution of palpable splenomegaly. All these criteria have to last at least 4 weeks.
In the ET Cohort, the ORR is defined as the proportion of subjects with Platelet count ≤ 400 x 10^9/L, WBC < 10 x 10^9/L and resolution of palpable splenomegaly. All these criteria have to last at least 4 weeks.
In order to be counted as a responder for PV and ET, a subject must meet all of the above criteria at some point during the treatment period. However, 4 criteria for PV or the 3 criteria for ET do not have to be met for the same 4 weeks. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Monitoring will be conducted intensively for the first 24 weeks (biweekly the first 8 weeks, and after every 4 weeks through week 24 / Early
Study Drug Discontinuation) of the study. |
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E.5.2 | Secondary end point(s) |
1. Confirmed ORR – defined as the proportion of subjects who meet all the criteria listed for the primary endpoints of PV or ET, sustained for at least 12 weeks. The 4 criteria for PV or the 3 criteria for ET do not have to be met for the same 12 weeks.
2. Proportion of subjects with hematocrit < 45% in the absence of phlebotomy that lasts at least 4 weeks
3. Proportion of subjects with WBC < 10 x 10^9/L that lasts at least 4 weeks
4. Proportion of subjects with platelet count ≤ 400 x 10^9/L that lasts at least 4 weeks
5. Proportion of subjects with resolution of palpable splenomegaly that lasts at least 4 weeks
6. Proportion of subjects with ≥ 10 point decrease in modified MPNSAF TSS compared to baseline that lasts at least 12 weeks |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Monitoring will be conducted intensively for the first 24 weeks (biweekly the first 8 weeks, and after every 4 weeks through week 24 / Early
Study Drug Discontinuation) of the study. |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
2 strengths of Momelotinib are compared. |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 |
Australia |
Canada |
France |
Germany |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |