This is a Phase 3, randomized, double-blind study of the combination of the PI3Kδ inhibitor
parsaclisib or matching placebo and the JAK1/2 inhibitor ruxolitinib in participants with PMF
or secondary MF (PPV-MF or PET-MF) with DIPSS risk category of intermediate or high.
Prospective participants must have not received prior MF therapy with a JAK inhibitor or a
PI3K inhibitor. After participants have been determined to be eligible for the study and
completed the baseline symptom diary assessment for 7 days, they will be randomized to 1 of 2
treatment groups, with stratification for platelet count (≥ 100 × 10^9/L vs 50 to < 100 ×
10^9/L inclusive) and DIPSS risk category (high vs intermediate-2 vs intermediate-1).
Once all enrolled participants completed the week 24 assessments the study will be unblinded
and and participants randomized to placebo will have the opportunity to cross over to begin
receiving parsaclisib, together with continued ruxolitinib, as long as hematology parameters
- 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
- 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.
- 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
- Inadequate recovery from toxicity and/or complications from a major surgery before
- 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