An Open Label Study of Itacitinib Administered Orally in Patients With Myelofibrosis

Study Overview
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Brief Summary
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This is a study of itacitinib (INCB039110) in patients with myelofibrosis. This study will evaluate safety and efficacy parameters of itacitinib (INCB039110).

Official Title
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An Open-Label, Multiple Simon 2-Stage Study of Itacitinib Administered Orally to Subjects With Primary Myelofibrosis (PMF), Post Polycythemia Vera Myelofibrosis (PPV-MF) or Post Essential Thrombocythemia Myelofibrosis (PET-MF)

Conditions
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MPN (Myeloproliferative Neoplasms)

Intervention / Treatment
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* Drug: itacitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be diagnosed with PMF, PPV-MF or PET-MF as confirmed by bone marrow biopsy. Must score at least 1 point on the Dynamic International Prognostic Scoring System (DIPSS) for prognostic risk factors and have peripheral blast count <10% at both Screening and Baseline hematology assessments. Subjects must discontinue all drugs used to treat underlying MF disease no later than Day -14. Subjects must have hemoglobin value >/= 8.0g/dL and be willing to receive blood transfusions, have a platelet count >/=50x10^9/L and absolute neutrophil count (ANC) >/= 1x10^9/L. Subjects must have palpable spleen or history of splenectomy Active symptoms at the screening visit Exclusion Criteria: Women who are pregnant or breastfeeding, and men and women who cannot comply with requirements to avoid fathering a child or becoming pregnant, respectively. Subjects with impaired liver function, end stage renal disease on dialysis or clinically significant concurrent infections requiring therapy. Subjects with unstable cardiac function or invasive malignancies over the previous 2 years except treated basal or squamous carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix and completely resected papillary thyroid and follicular thyroid cancers.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: itacitinib 100 mg<br>itacitinib 100 mg twice a day | Drug: itacitinib<br> <br> * Other names: INCB039110;|
| Experimental: itacitinib 200 mg<br>itacitinib 200 mg twice a day | Drug: itacitinib<br> <br> * Other names: INCB039110;|
| Experimental: itacitinib 300 mg<br>itacitinib 300 mg once a day | Drug: itacitinib<br> <br> * Other names: INCB039110;|
| Experimental: itacitinib 400 mg<br>itacitinib 400 mg once a day | Drug: itacitinib<br> <br> * Other names: INCB039110;|
| Experimental: itacitinib 600 mg<br>itacitinib 600 mg once a day | Drug: itacitinib<br> <br> * Other names: INCB039110;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with >/= 50% reduction in total symptom score in each dose group, as measured by the modified The Myelofibrosis Symptom Assessment Form (MFSAF) v3.0 diary |  | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with >/= 35% reduction in spleen volume, and mean percent change in spleen volume |  | Baseline, Week 12 and Week 24 | 
| Proportion of transfusion dependent subjects who exhibit changes in transfusion frequency over any 12 week period on study and proportion of transfusion independent subjects who exhibit changes in hemoglobin level |  | Baseline to Week 12; Week 13 to Week 24 through the end of study or study termination visit. | 
| Safety and tolerability of itacitinib as measured by adverse events. |  | Every 4-6 weeks through the end of study or early termination visit (approximately 33 weeks exclusive of the extension phase). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary Myelofibrosis, PMF, Post Polycythemia Vera Fibrosis, PPV-MF, Post Essential Thrombocythemia Myelofibrosis, PET-MF