Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Tablets Versus Best Available Care: (The RESPONSE Trial)

Study Overview
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Brief Summary
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This pivotal phase III trial (CINC424B2301) is designed to compare the efficacy and safety of ruxolitinib (INC424) to Best Available Therapy (BAT) in participants with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea (HU).

Official Title
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Randomized, Open Label, Multicenter Phase III Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 Tablets Versus Best Available Care (The RESPONSE Trial)

Conditions
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Polycythemia Vera

Intervention / Treatment
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* Drug: ruxolitinib tablets
* Other: Best Available Therapy (BAT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants diagnosed with PV for at least 24 weeks prior to screening according to the 2008 World Health Organization criteria Participants resistant to or intolerant of hydroxyurea Participants with a phlebotomy requirement Participants with splenomegaly (palpable or non-palpable) and a spleen volume, as measured by MRI (or CT in applicable participants ), of greater than or equal to 450 cubic centimeters Participants with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 Exclusion Criteria: Women who are pregnant or nursing Participants with inadequate liver or renal function Participants with significant bacterial, fungal, parasitic, or viral infection requiring treatment Participants with an active malignancy within the past 5 years, excluding specific skin cancers Participants with known active hepatitis or HIV positivity Participants who have previously received treatment with a JAK inhibitor Participants being treated with any investigational agent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ruxolitinib tablets<br>Starting dose of 10 mg BID with individualized dose titration ranging from 5 mg once a day (QD) to 25 mg BID based on safety and efficacy | Drug: ruxolitinib tablets<br>* Starting dose of 10 mg BID with individualized dose titration ranging from 5 mg QD to 25 mg BID based on safety and efficacy<br>|
| Other: Best Available Therapy<br>Best Available Therapy (BAT) will be selected by the Investigator for each participant. BAT may not include experimental agents (i.e. those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements. | Other: Best Available Therapy (BAT)<br>* Best Available Therapy (BAT) will be selected by the Investigator for each participant. BAT may not include experimental agents (i.e. those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements.<br>* Other names: Observation only;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants Achieving a Primary Response at Week 32 | Primary response was defined as having achieved hematocrit control (the absence of phlebotomy eligibility beginning at the Week 8 visit and continuing through Week 32) and Spleen Volume Reduction (a greater than or equal to 35% reduction from baseline in spleen volume at Week 32). | 32 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants Achieving a Durable Primary Response at Week 48 | Durable Primary Response was defined as any participant who achieved the primary outcome measure and who maintained their response up to 48 weeks after randomization. | 48 Weeks | 
| The Percentage of Participants Achieving Complete Hematological Remission at Week 32 | Complete Hematological Remission at Week 32 was defined as any participant who achieved hematocrit control with a platelet count less than or equal to 400 X 10^9/L and a white blood cell count less than or equal to 10 X 10^9/L. | 32 Weeks | 
| The Percentage of Participants Who Achieved a Durable Complete Hematological Remission at Week 48 | Durable Complete Hematological Remission was defined as any participant who achieved Complete Hematological Remission at Week 32 and maintained their response up to 48 weeks after randomization. | 48 Weeks | 
| The Percentage of Participants Who Achieved a Durable Hematocrit Control at Week 48 | Durable Hematocrit Control was defined as any participant who achieved phlebotomy eligibility independence from Week 8 to Week 32 and maintained hematocrit control up to 48 weeks after randomization. | 48 Weeks | 
| The Percentage of Participants Who Achieved Durable Spleen Volume Reduction at Week 48 | Durable Spleen Volume Reduction was defined as a participant who achieved at least 35% reduction from baseline in spleen volume at Week 32 and maintained that response 48 weeks after randomization. | 48 Weeks | 
| Estimated Duration of the Primary Response | Duration of the primary response is defined as the time from the first occurrence when both components of the primary endpoint are met until the date of the first documented disease progression (end of response). Kaplan-Meier estimates are provided for duration of primary response. | Through study completion, analysis was conducted when all participants had completed the Week 80 visit or discontinued the study | 
| The Percentage of Participants Who Achieved Overall Clinicohematologic Response at Week 32 | Overall Clinicohematologic Response is defined as any participant who achieved a complete or partial clinicohematologic response per the European LeukemiaNet modified criteria for response in polycythemia vera (PV). A Complete Response (CR) is defined as: hematocrit control, spleen volume reduction at least 35% from baseline, platelet count less than or equal to 400 x 10(9)/L, and white blood cell count less than or equal to 10 x 10(9)/L. A Partial Response (PR) is defined as hematocrit control or response in all 3 of the other criteria. | 32 Weeks | 
| The Percentage of Participants Achieving a Durable Complete or Partial Clinicohematologic Response at Week 48 | Durable Complete or Partial Clinicohematologic Response was defined as any participant who achieved complete or partial clinicohematologic response per the European LeukemiaNet modified criteria for response in polycythemia vera at Week 32 and maintained that response 48 weeks after randomization. | 48 Weeks | 
| Estimated Duration of the Complete Hematological Remission | Duration of the complete hematological remission is defined as the time from the first occurrence of complete hematological remission until the date of the first documented progression (end of response). Kaplan-Meier estimates are provided for duration of complete hematological remission. | Through study completion, analysis was conducted when all participants had completed the Week 80 visit or discontinued the study | 
| Duration of the Absence of Phlebotomy Eligibility | Duration of the absence of phlebotomy eligibility is defined as the time from the first occurrence of absence of phlebotomy eligibility until the date of the first documented progression. | 256 Weeks | 
| Duration of Reduction in Spleen Volume | Duration of spleen volume reduction is defined as the time from the first occurrence of a >=35% reduction from baseline in spleen volume until the date of the first documented progression. | 256 Weeks | 
| Duration of The Overall Clinicohematologic Response | Duration of the overall clinicohematologic response was defined as the time from the first occurrence of complete response (CR) or partial response (PR) until the date of the first documented disease progression. | 256 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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INCB018424