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) ((RESPONSE))

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT01243944
First received: November 17, 2010
Last updated: March 12, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
Polycythemia Vera
Drug: INC424 tablets
Other: Best Available Therapy (BAT)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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 INC424 Tablets Versus Best Available Care

Resource links provided by NLM:


Further study details as provided by Incyte Corporation:

Primary Outcome Measures:
  • To compare the efficacy of INC424 to Best Available Therapy as assessed by both the absence of phlebotomy eligibility and reduction in spleen volume. [ Time Frame: 32 Weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To compare the proportion of subjects randomized to INC424 vs. Best Available Therapy achieving both durable absence of phlebotomy eligibility and durable spleen volume reduction. [ Time Frame: 48 Weeks. ] [ Designated as safety issue: No ]
  • To compare the proportion of subjects randomized to INC424 vs. Best Available Therapy achieving complete hematological remission. [ Time Frame: 32 Weeks ] [ Designated as safety issue: No ]
  • To determine the proportion of subjects achieving a durable spleen volume reduction [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • To estimate the proportion of subjects achieving a durable complete hematological remission [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • To estimate the proportion of subjects achieving a durable phlebotomy independence [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • To estimate the duration of both the absence of phlebotomy eligibility and reduction in spleen volume [ Time Frame: Through study completion ] [ Designated as safety issue: No ]
  • To determine the overall clinicohematologic response rate [ Time Frame: 32 Weeks ] [ Designated as safety issue: No ]
  • To estimate the proportion of subjects achieving a durable complete or partial clinicohematologic response [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • To estimate the duration of the overall clinicohematologic response [ Time Frame: Through study completion ] [ Designated as safety issue: No ]
  • To estimate the proportion of subjects achieving both durable absence of phlebotomy eligibility and durable spleen volume reduction 48 weeks after the response was initially documented [ Time Frame: Through study completion. ] [ Designated as safety issue: No ]
  • Safety and tolerability of INC424 as measured by adverse events, laboratory assessments, physical examination, vital signs, and ECG measurements. [ Time Frame: Through study completion ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: October 2010
Estimated Study Completion Date: September 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: INC424 tablets
Starting dose of 10 mg BID with individualized dose titration ranging from 5 mg QD to 25 mg BID based on safety and efficacy
Drug: INC424 tablets
Starting dose of 10 mg BID with individualized dose titration ranging from 5 mg QD to 25 mg BID based on safety and efficacy
Best Available Therapy
Best Available Therapy (BAT) will be selected by the Investigator for each subject. 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.
Other: Best Available Therapy (BAT)
Best Available Therapy (BAT) will be selected by the investigator for each subject. 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.
Other Names:
  • BAT:
  • 1. Hydroxyurea
  • 2. IFN/PEG-IFN
  • 3. Pipobroman
  • 4. Anagrelide
  • 5. IMIDs
  • 6. Observation only

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects diagnosed with PV for at least 24 weeks prior to screening according to the 2008 World Health Organization criteria
  • Subjects resistant to or intolerant of hydroxyurea
  • Subjects with a phlebotomy requirement
  • Subjects with a palpable splenomegaly and a spleen volume of greater than or equal to 450 cubic centimeters
  • Subjects with an ECOG performance status of 0, 1 or 2

Exclusion Criteria:

  • Women who are pregnant or nursing
  • Subjects with inadequate liver or renal function
  • Subjects with significant bacterial, fungal, parasitic, or viral infection requiring treatment
  • Subjects with an active malignancy within the past 5 years, excluding specific skin cancers
  • Subjects with known active hepatitis or HIV positivity
  • Subjects who have previously received treatment with a JAK inhibitor
  • Subjects being treated with any investigational agent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01243944

  Show 160 Study Locations
Sponsors and Collaborators
Incyte Corporation
Novartis Pharmaceuticals
Investigators
Study Director: Srdan Verstovsek, MD,PhD M.D. Anderson Cancer Center
Study Director: Mark Jones, MD Incyte Corporation
  More Information

Additional Information:
No publications provided

Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT01243944     History of Changes
Other Study ID Numbers: CINC424B2301
Study First Received: November 17, 2010
Last Updated: March 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Incyte Corporation:
INCB018424

Additional relevant MeSH terms:
Polycythemia
Polycythemia Vera
Hematologic Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hydroxyurea
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antisickling Agents
Hematologic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014