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To Evaluate Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib (LIMBER-304)

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ClinicalTrials.gov Identifier: NCT04551053
Recruitment Status : Recruiting
First Posted : September 16, 2020
Last Update Posted : August 4, 2021
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Tracking Information
First Submitted Date  ICMJE September 11, 2020
First Posted Date  ICMJE September 16, 2020
Last Update Posted Date August 4, 2021
Actual Study Start Date  ICMJE May 26, 2021
Estimated Primary Completion Date November 28, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 11, 2020)
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2020)
  • 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.
  • Change in TSS [ Time Frame: Baseline to Week 24 ]
    Change in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.
  • 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.
  • Overall Survival (OS) [ Time Frame: Up to approximately 36 months ]
    OS is defined as randomization date to death due to any cause
  • 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.
  • Time of onset of targeted reduction in spleen volume [ Time Frame: Baseline to Week 108 ]
    Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).
  • Duration of maintenance of targeted reduction in spleen volume [ Time Frame: Baseline to Week 108 ]
    Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE To Evaluate Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib (LIMBER-304)
Official Title  ICMJE A Randomized, Double-Blind, Placebo-Controlled Study of the PI3Kδ Inhibitor Parsaclisib Plus Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib
Brief Summary The purpose of the study is to compare the efficacy and safety of parsaclisib when combined with ruxolitinb versus placebo combined with ruxolitinib in participants with myelofibrosis who have suboptimal response while receiving ruxolitinib monotherapy.
Detailed Description

Prospective participants must be on stable doses of ruxolitinib ranging from 5 mg BID to 25 mg BID and will have been on that dose for at least the last 8 weeks prior to Day 1. At least 3 months duration of prior ruxolitinib is required. Participants must meet Protocol-defined criteria for suboptimal response to ruxolitinib monotherapy. 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 a participant has completed the week 24 assessments, the participant's treatment assignment will then be unblinded and if found to be placebo, the participant will have the opportunity to crossover to begin receiving parsaclisib, together with continued ruxolitinib, as long as hematology parameters are adequate.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
Triple blind
Primary Purpose: Treatment
Condition  ICMJE
  • Myelofibrosis
  • Primary Myelofibrosis
  • Post Essential Thrombocythemia Myelofibrosis
  • Post Polycythemia Vera Myelofibrosis
Intervention  ICMJE
  • Drug: parsaclisib
    parsaclisib will be administered QD orally
    Other Name: INCB050465
  • Drug: ruxolitinib
    ruxolitinib will be administered BID orally
    Other Names:
    • Jakafi
    • Jakavi
  • Drug: placebo
    placebo will be administered QD orally
Study Arms  ICMJE
  • Experimental: Group A : ruxolitinib +parsaclisib
    Participants will receive parsaclisib starting from Day 1 for the duration of study, while continuing to receive the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1.
    Interventions:
    • Drug: parsaclisib
    • Drug: ruxolitinib
  • Placebo Comparator: Group B : ruxolitinib + placebo
    Participants will receive placebo starting from Day 1 for the duration of study, while continuing to receive the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1.
    Interventions:
    • Drug: ruxolitinib
    • Drug: placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 11, 2020)
212
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date November 28, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of PMF, PPV-MF, or PET-MF.
  • DIPSS risk category of intermediate-1, intermediate-2, or high.
  • Treated with ruxolitinib for ≥ 3 months with a stable dose for at least the last 8 weeks prior to Day 1
  • 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 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 used for MF (eg, danazol, hydroxyurea) with the exception of ruxolitinib, within 3 months of starting study drug, and/or lack of recovery from all toxicities from previous therapy (except ruxolitinib) to Grade 1 or better.
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE Austria,   Belgium,   China,   Finland,   France,   Germany,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Norway,   Poland,   Romania,   Russian Federation,   Spain,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries Denmark
 
Administrative Information
NCT Number  ICMJE NCT04551053
Other Study ID Numbers  ICMJE INCB 50465-304/LIMBER-304
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: 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
Responsible Party Incyte Corporation
Study Sponsor  ICMJE Incyte Corporation
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Albert Assad, M.D. Incyte Corporation
PRS Account Incyte Corporation
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP