E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Myelofibrosis or Secondary Myelofibrosis |
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E.1.1.1 | Medical condition in easily understood language |
Primary Myelofibrosis or Secondary Myelofibrosis |
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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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Part 1: To evaluate the safety and tolerability of itacitinib IR and select the RP2D for Part 2 of the study. Part 2: To evaluate the efficacy of itacitinib IR at the RP2D with respect to spleen volume reduction at Week 24. |
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E.2.2 | Secondary objectives of the trial |
Part 2: - To evaluate the safety and tolerability of itacitinib IR at the RP2D. - To evaluate the efficacy of itacitinib IR at the RP2D with respect to MF symptom improvement at Week 24, in those patients with a baseline TSS ≥ 10. - To evaluate the efficacy of itacitinib IR with respect to improvement of quality of life. - To evaluate the efficacy of itacitinib IR at the RP2D with respect to PGIC. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Aged 18 years or older at the time of signing the informed consent 2. Diagnosis of primary MF meeting the 2016 WHO criteria for overt PMF or secondary MF (PPV-MF or PET-MF) meeting the 2008 IWG-MRT criteria. 3. At least Intermediate 1 risk MF according to the DIPSS. 4. Prior treatment with ruxolitinib and/or fedratinib monotherapy: a. Previously treated with ruxolitinib and/or fedratinib monotherapy for PMF or secondary MF for not more than 6 months if treatment was discontinued due to recurrent Grade 4 thrombocytopenia; ≥ Grade 3 anemia, hemorrhage, or hematoma; or allergy/other intolerance to ruxolitinib or fedratinib OR b. Currently receiving ruxolitinib or fedratinib monotherapy for PMF or secondary MF: − For at least 3 months with initial response but regrowth of spleen on imaging or by palpation compared with baseline; OR − For at least 28 days if treatment is complicated by recurrent Grade 4 thrombocytopenia; ≥ Grade 3 anemia, hemorrhage, or hematoma; or allergy/other intolerance to ruxolitinib or fedratinib. 5. Splenomegaly defined as palpable spleen at least 5 cm below the left costal margin or volume ≥ 450 cm3 on imaging assessed during screening. 6. Allogeneic stem cell transplant not planned. 7. Platelet ≥ 50 × 109/L at screening. 8. Ability to comprehend and willingness to sign a written ICF for the study. 9. Willingness to avoid pregnancy or fathering children |
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E.4 | Principal exclusion criteria |
1. Prior treatment with a JAK inhibitor other than ruxolitinib or fedratinib 2. Record of ≥ 10% myeloid blasts in the peripheral blood (on peripheral blood smear) or bone marrow prior to or at the time of screening 3. For participants on ruxolitinib or fedratinib, unable to be tapered from that treatment over the course of 14 days without corticosteroids, hydroxyurea, or other agents 4. Treatment with ruxolitinib, fedratinib or other MF-directed therapy (approved or investigational) within 2 weeks of Day 1 5. Prior splenectomy or splenic irradiation within 6 months before receiving the first dose of itacitinib 6. Unable or unwilling to undergo serial MRI or CT scans for spleen volume measurement 7. Unable or unwilling to complete MFSAF v4.0 diary on a daily basis during the study 8. ECOG performance status ≥ 3 9. Life expectancy less than 24 weeks 10. Not willing to receive RBC or platelet transfusions 11. Participants with laboratory values at screening defined in Table 11 of protocol 12. Significant concurrent, uncontrolled medical condition, including but not limited to the following: Gastrointestinal, Cardiovascular 13. History or presence of an abnormal ECG that, in the investigator’s opinion, is clinically meaningful according to the guidance provided in Section 8.3.4 of the protocol. 14. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment. 15. Hepatitis: Evidence of HBV or HCV infection or risk of reactivation. 16. Known HIV infection. 17. Current use of prohibited medication as described in Section 6.6.9 of protocol. 18. Inability or unlikeliness of the participant to comply with the dose schedule and study evaluations, in the opinion of the investigator. 19. Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy. 20. Women who are pregnant or breastfeeding. 21. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of itacitinib IR and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data. 22. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including: inability to self-administer itacitinib IR; difficulty attending required study visits; a comorbid condition that poses a significant risk to the participant or may interfere with interpretation of study data. 23. The following participants are excluded in France: vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection or who are unable to express their consent per article L.1121-8 of the French Public Health Code. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part 1: Safety and tolerability through assessments of frequency and severity of AEs; changes in clinical safety assessments; changes in clinical laboratory parameters. Part 2: SRR at Week 24, where SRR is defined as the proportion of participants who have a reduction in spleen volume (by imaging) of at least 35% when compared with baseline
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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) |
Safety and tolerability through assessments of frequency and severity of AEs; changes in clinical safety assessments; changes in clinical laboratory parameters. TSS response rate at Week 24, where TSS response is defined as the proportion of participants who achieve at least 50% reduction in TSS over the 28 days immediately before the end of Week 24 compared with the 7 days immediately before initiation of itacitinib IR (baseline). The mean change (from Day 1 vs Week 12 and Week 24) in the 5 multi-item functional scale scores and the multi-item global health status scale score (EORTC QLQ-C30). |
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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 | 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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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.8.3 |
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 | 34 |
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 |
United States |
Austria |
Belgium |
France |
Germany |
Italy |
Poland |
Spain |
United Kingdom |
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E.8.7 | Trial 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
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |