Myeloproliferative Neoplasms
Conditions
Keywords
Myeloproliferative Neoplasms, INCB160058, Myelofibrosis
Brief summary
This study is being conducted to assess the Safety, Tolerability, and Pharmacokinetics of INCB160058 in Participants With Myeloproliferative Neoplasms.
Interventions
DRUGINCB160058
Oral; Tablet
A standard disease-directed therapy will be administered according to Prescribing Information/SmPC.
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * MF: * Intermediate-1 or higher risk PMF, post-PV MF, or post-ET MF with evidence of minimum burden of disease based on splenomegaly, and for the monotherapy cohort, participants must have been previously treated with at least 1 JAK inhibitor for ≥ 12 weeks and resistant, refractory, intolerant to, or have lost response to JAK inhibitor treatment. * For the MF SubOpt R cohort: Therapeutic regimen prior to enrollment as defined in the protocol and unlikely to benefit from further monotherapy in the opinion of the investigator. * PV: Confirmed diagnosis of PV and previously treated with at least 1 prior standard cytoreductive therapy and are resistant, refractory, intolerant to, or have lost response to treatment. * ET: Confirmed diagnosis of high-risk ET as defined in the protocol and previously treated with at least 1 prior standard cytoreductive therapy and are resistant, refractory, intolerant to, or have lost response to treatment. * Life expectancy \> 6 months. * Willingness to undergo a pretreatment and regular on-study bone marrow biopsies and aspirations (as appropriate to disease). * Existing documentation of JAK2V617F mutation from a qualified local laboratory.
Exclusion criteria
* Presence of a hematological malignancy requiring treatment, other than PMF, post-PV MF, post-ET MF, PV, or ET. * Prior history of major bleeding or thrombosis within the 3 months prior to study enrollment. * Participants with abnormal hematologic, hepatic, or renal function based on laboratory evaluation. * Has undergone prior allogenic or autologous stem-cell transplantation or allogenic stem-cell transplantation is planned * Active invasive malignancy. * Significant concurrent, uncontrolled medical condition. * Acute or chronic HBV, active HCV or known HIV. * Any prior MPN-directed therapy within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment. * Participants undergoing treatment with G-CSF or GM-CSF, romiplostim, or eltrombopag at any time within 4 weeks before the first dose of study treatment. Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Dose Limiting Toxicities (DLTs) | Up to 28 days | Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol. |
| Number of participants with Treatment-emergent Adverse Events (TEAEs) | Up to 2 years and 30 days | Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug. |
| Number of participants with TEAEs leading to dose modification or discontinuation | Up to 2 years and 30 days | Number of participants with TEAEs leading to dose modification or discontinuation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| INCB160058 and a standard disease-directed therapy pharmacokinetic (PK) in Plasma | Up to Day 57 | INCB160058 and the protocol defined standard disease-directed therapy concentration in plasma. |
| For participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF | Week 12 and 24 and then every 24 weeks up to 2 years | Defined as the percentage of participants with Response using the revised International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) response criteria. |
| For participants with MF: Percentage of participants achieving spleen volume reduction as defined in the protocol | Week 12 and Week 24 | Defined as percentage of participants with a protocol defined Spleen Volume Reduction. |
| For participants with PV: Response using revised IWG-MRT and ELN response criteria for PV | Week 12 and 24 and then every 24 weeks up to 2 years | Defined as the percentage of participants with Response using the revised International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) response criteria. |
| For participants with ET: Response using revised IWG-MRT and ELN response criteria for ET | Week 12 and 24 and then every 24 weeks up to 2 years | Defined as the percentage of participants with Response using the revised International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) response criteria. |
| For all participants: Percentage of participants achieving ≥ 50% reduction from baseline of total symptom score (TSS) | Week 24 | Defined as the percentage of participants achieving ≥ 50% reduction from baseline of TSS. |
| For all participants: Symptom improvement in TSS at Weeks 12 and 24 relative to baseline as measured by the Myeloproliferative Neoplasms Symptom Assessment Form (MPN-SAF) TSS. | Week 12 and Week 24 | Defined as the proportion of participants who achieve a protocol defined reduction in Total Symptomatic Score (TSS) relative to baseline as measured by the MPN-SAF TSS. |
Countries
Canada, France, Germany, Italy, Norway, Switzerland, United Kingdom, United States
Contacts
STUDY_DIRECTORIncyte Medical
Incyte Corporation
Outcome results
None listed