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) - Full Text View

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:

Genetics Home Reference related topics: polycythemia vera

Drug Information available for: Hydroxyurea

Genetic and Rare Diseases Information Center resources: Chronic Myeloproliferative Disorders Polycythemia Vera

U.S. FDA Resources

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:

Related Info This link exits the ClinicalTrials.gov site

No publications provided by Incyte Corporation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. doi: 10.1056/NEJMoa1409002.


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 Bone Marrow Diseases Hematologic Diseases Myeloproliferative Disorders Hydroxyurea Antineoplastic Agents	Antisickling Agents Enzyme Inhibitors Hematologic Agents Molecular Mechanisms of Pharmacological Action Nucleic Acid Synthesis Inhibitors Pharmacologic Actions Therapeutic Uses

ClinicalTrials.gov processed this record on February 25, 2015

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))