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To Evaluate the Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis (LIMBER-313)

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ClinicalTrials.gov Identifier: NCT04551066
Recruitment Status : Recruiting
First Posted : September 16, 2020
Last Update Posted : September 17, 2021
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Brief Summary:
The purpose of the study is to compare the efficacy of parsaclisib when combined with ruxolitinb versus placebo combined with ruxolitinib in participants with myelofibrosis.

Condition or disease Intervention/treatment Phase
Myelofibrosis Primary Myelofibrosis Post Essential Thrombocythemia Myelofibrosis Post Polycythemia Vera Myelofibrosis Drug: parsaclisib Drug: ruxolitinib Drug: placebo Phase 3

Detailed Description:

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 are adequate.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 440 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: Triple blind
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Combination of PI3Kδ Inhibitor Parsaclisib and Ruxolitinib in Participants With Myelofibrosis
Actual Study Start Date : May 24, 2021
Estimated Primary Completion Date : November 22, 2023
Estimated Study Completion Date : May 23, 2026


Arm Intervention/treatment
Experimental: Group A : parsaclisib + ruxolitinib
Participants will receive parsaclisib and ruxolitinib starting from Day 1 for the duration of study, ruxolitinib dose will be determined by baseline platelet count.
Drug: parsaclisib
parsaclisib will be administered QD orally
Other Name: INCB050465

Drug: ruxolitinib
ruxolitinib will be administered BID orally
Other Names:
  • Jakafi
  • Jakavi

Placebo Comparator: Group B : placebo + ruxolitinib
Participants will receive placebo and ruxolitinib starting from Day 1 for the duration of study, ruxolitinib dose will be determined by baseline platelet count.
Drug: ruxolitinib
ruxolitinib will be administered BID orally
Other Names:
  • Jakafi
  • Jakavi

Drug: placebo
placebo will be administered QD orally




Primary Outcome Measures :
  1. Proportion of participants achieving targeted reduction in spleen volume [ Time Frame: Baseline to Week 24 ]
    Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).


Secondary Outcome Measures :
  1. Proportion of participants who have a targeted reduction in Total Symptom Score (TSS) [ Time Frame: Baseline to Week 24 ]
    Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.

  2. Change in TSS [ Time Frame: Baseline to Week 24 ]
    Change in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.

  3. Time to the first ≥ 50% reduction in TSS [ Time Frame: Baseline to Week 24 ]
    Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.

  4. Overall Survival (OS) [ Time Frame: Up to approximately 36 months ]
    OS is defined as randomization date to death due to any cause.

  5. Number of Treatment Emergent Adverse Events (TEAE) [ Time Frame: Up to approximately 36 months ]
    Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug up to 35 days after last dose of study drug.

  6. Time of onset of targeted reduction in spleen volume [ Time Frame: Baseline to Week 144 ]
    Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).

  7. Duration of maintenance of targeted reduction in spleen volume [ Time Frame: Baseline to Week 144 ]
    Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion 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.

Exclusion 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04551066


Contacts
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Contact: Incyte Corporation Call Center (US) 1.855.463.3463 medinfo@incyte.com
Contact: Incyte Corporation Call Center (ex-US) +800 00027423 eumedinfo@incyte.com

Locations
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Sponsors and Collaborators
Incyte Corporation
Investigators
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Study Director: Albert Assad, M.D Incyte Corporation
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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT04551066    
Obsolete Identifiers: NCT04816578
Other Study ID Numbers: INCB 50465-313/LIMBER-313
First Posted: September 16, 2020    Key Record Dates
Last Update Posted: September 17, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
URL: https://www.incyte.com/our-company/compliance-and-transparency

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Incyte Corporation:
INCB050465
ruxolitinib
parsaclisib
LIMBER
MF
Myelofibrosis
Myeloproliferative Neoplasms
Myoproliferative Neoplasms
Additional relevant MeSH terms:
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Polycythemia Vera
Primary Myelofibrosis
Polycythemia
Thrombocytosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders