A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Combination of PI3K delta Inhibitor Parsaclisib and Ruxolitinib in Participants With Myelofibrosis

JRCT ID: jRCT2071200114

Registered date:17/03/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Myelofibrosis, (Primary, Post Essential Thrombocythemia, Post Polycythemia Vera) Myelofibrosis
• Date of first enrollment: 16/07/2021
• Target sample size: 252
• Countries of recruitment: U.S.A,Japan,Austria,Japan,Belgium,Japan,China,Japan,Denmark,Japan,Finland,Japan,France,Japan,Germany,Japan,Israel,Japan,Italy,Japan,Korea,Japan,Norway,Japan,Poland,Japan,Spain,Japan,Turkey,Japan,United Kingdom,Japan
• Study type: Interventional

Intervention(s)

Parallel Assignment
Group A : parsaclisib + ruxolitinib
parsaclisib (INCB050465) will be administered QD orally.
ruxolitinib will be administered BID orally.

Group B : placebo + ruxolitinib
placebo will be administered QD orally.
ruxolitinib will be administered BID orally.

Outcome(s)

• Primary Outcome: Proportion of participants achieving targeted reduction in spleen volume [ Time Frame: Baseline to Week 24 ]

Secondary Outcome

1. Proportion of participants who have a targeted reduction in Total Symptom Score (TSS) [ Time Frame: Baseline to Week 24 ]
2. Change in TSS [ Time Frame: Baseline to Week 24 ]
3. Time to the first >= 50% reduction in TSS [ Time Frame: Baseline to Week 24 ]
4. Overall Survival (OS) [ Time Frame: Up to approximately 36 months ]
5. Number of Treatment Emergent Adverse Events (TEAE) [ Time Frame: Up to approximately 36 months ]
6. Time of onset of targeted reduction in spleen volume [ Time Frame: Baseline to Week 144 ]
7. Duration of maintenance of targeted reduction in spleen volume [ Time Frame: Baseline to Week 144 ]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Diagnosis of PMF, PPV-MF, or PET-MF.
- DIPSS risk category of intermediate-1, intermediate-2, or high.
- Palpable spleen of >= 5 cm below the left costal margin on physical examination at the screening visit.
- Active symptoms of MF at the screening visit, as demonstrated by the presence of a TSS of >= 10 using the Screening Symptom Form.
- Participants with an ECOG performance status score of 0, 1, or 2.
- Screening bone marrow biopsy specimen and pathology report(s) available that was obtained within the prior 2 months or willingness to undergo a bone marrow biopsy at screening/baseline; willingness to undergo bone marrow biopsy at Week 24 and every 24 weeks there after. Screening/baseline biopsy specimen must show diagnosis of MF.
- Life expectancy of at least 24 weeks.
- Willingness to avoid pregnancy or fathering children.

Exclude criteria

- Prior use of any JAK inhibitor.
- Prior therapy with any drug that inhibits PI3K (examples of drugs targeting this pathway include but are not limited to INCB040093, idelalisib, duvelisib, buparlisib, copanlisib, and umbralisib).
- Use of experimental drug therapy for MF or any other standard drug (eg, danazol, hydroxyurea) used for MF within 3 months of starting study drug and/or lack of recovery from all toxicities from previous therapy to <= Grade 1.
- Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
- Recent history of inadequate bone marrow reserve.
- Inadequate liver and renal function at screening.
- Active bacterial, fungal, parasitic, or viral infection that requires therapy.
- Active HBV or HCV infection that requires treatment or at risk for HBV reactivation.
- Known HIV infection.
- Uncontrolled, severe, or unstable cardiac disease that in the investigator's opinion may jeopardize the safety of the participant or compliance with the Protocol.
- Active invasive malignancy over the previous 2 years.
- Splenic irradiation within 6 months before receiving the first dose of study drug.
- Concurrent use of any prohibited medications.
- Active alcohol or drug addiction that would interfere with the ability to comply with the study requirements.
- Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half lives(whichever is longer) before the first dose of study drug or anticipated during the study.
- Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.
- Currently breastfeeding or pregnant.
- Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
- History of Grade 3 or 4 irAEs from prior immunotherapy.
- Receipt of any live vaccine within 30 days of the first dose of study drug

Related Information

• Primary Sponsor: Ueda Eiji
• Secondary ID(s): NCT04551066