Clinical Trial: 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 Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: 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 I

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

Detailed Summary:
Sponsor: Incyte Corporation

Current Primary Outcome: The Percentage of Subjects Achieving a Primary Response at Week 32 [ Time Frame: 32 Weeks ]

Original Primary Outcome: Proportion of subjects achieving a response at Week 32. 'Response' is defined as having achieved both: (1) the absence of protocol-defined phlebotomy eligibility and (2) a ≥ 35% reduction from baseline in spleen volume as determined by imaging [ Time Frame: 32 weeks ]

Current Secondary Outcome:

• The Percentage of Subjects Achieving a Durable Primary Response at Week 48 [ Time Frame: 48 Weeks ]
  Durable Primary Response was defined as any subject who achieved the primary outcome measure and who maintained their response up to 48 weeks after randomization.
• The Percentage of Subjects Achieving Complete Hematological Remission at Week 32 [ Time Frame: 32 Weeks ]
  Complete Hematological Remission at Week 32 was defined as any subject 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.
• The Percentage of Subjects Who Achieved a Durable Complete Hematological Remission at Week 48 [ Time Frame: 48 Weeks ]
  Durable Complete Hematological Remission was defined as any subject who achieved Complete Hematological Remission at Week 32 and maintained their response up to 48 weeks after randomization.
• The Percentage of Subjects Who Achieved a Durable Hematocrit Control at Week 48 [ Time Frame: 48 Weeks ]
  Durable Hematocrit Control was defined as any subject who achieved phlebotomy eligibility independence from Week 8 to Week 32 and maintained hematocrit control up to 48 weeks after randomization.
• The Percentage of Subjects Who Achieved Durable Spleen Volume Reduction at Week 48 [ Time Frame: 48 Weeks ]
  Durable Spleen Volume Reduction was defined as a subject who achieved at least 35% reduction from baseline in spleen volume at Week 32 and maintained that response 48 weeks after randomization.
• Estimated Duration of the Primary Response [ Time Frame: Through study completion, analysis was conducted when all patients had completed the Week 80 visit or discontinued the study ]

  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.

• The Percentage of Subjects Who Achieved Overall Clinicohematologic Response at Week 32 [ Time Frame: 32 Weeks ]
  Overall Clinicohematologic Response is defined as any subject 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.
• The Percentage of Subjects Achieving a Durable Complete or Partial Clinicohematologic Response at Week 48 [ Time Frame: 48 Weeks ]
  Durable Complete or Partial Clinicohematologic Response was defined as any subject 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.
• Estimated Duration of the Complete Hematological Remission [ Time Frame: Through study completion, analysis was conducted when all patients had completed the Week 80 visit or discontinued the study ]

  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.

Original Secondary Outcome:

• Proportion of subjects achieving complete hematologic remission at Week 32. [ Time Frame: 32 weeks ]
• Proportion of all randomized subjects who both achieve the Week 32 primary response endpoint and maintain response for ≥ 48 weeks from the time that response was initially documented. [ Time Frame: At least 80 weeks ]

Dates:
Date Received: November 17, 2010
Date Started: October 2010
Date Completion: December 2018
Last Updated: September 21, 2016
Last Verified: September 2016