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Polycythemia VeraPhase 3NCT01243944

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)

A Phase 3 study testing ruxolitinib tablets and Best Available Therapy (BAT) in people with Polycythemia Vera, run by Incyte Corporation at 102 sites in 18 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Polycythemia Vera
What is being tested?
ruxolitinib tablets and Best Available Therapy (BAT)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
222 participants
Where
102 sitesin 18 countries
Study dates
27 Oct 2010to 9 Feb 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

102 sites in 18 countries.

102 sites in 18 countries

United States28 sites

  • Study site

    Baltimore, Maryland

  • Study site

    Birmingham, Alabama

  • Study site

    Boise, Idaho

  • Study site

    Boynton Beach, Florida

  • Study site

    Bridgeport, Connecticut

  • Study site

    Charleston, South Carolina

  • Study site

    Chicago, Illinois

  • Study site

    Columbia, Maryland

  • Study site

    Fort Myers, Florida

  • Study site

    Greenville, South Carolina

  • Study site

    Houston, Texas

  • Study site

    Jacksonville, Florida

  • Study site

    Jefferson City, Missouri

  • Study site

    Lafayette, Louisiana

  • Study site

    Morristown, New Jersey

  • Study site

    Nashville, Tennessee

  • Study site

    New Haven, Connecticut

  • Study site

    Omaha, Nebraska

  • Study site

    Pomona, California

  • Study site

    Sacramento, California

  • Study site

    San Diego, California

  • Study site

    Scarborough, Maine

  • Study site

    Scottsdale, Arizona

  • Study site

    Seattle, Washington

  • Study site

    Somerville, New Jersey

  • Study site

    Southfield, Michigan

  • Study site

    St Louis, Missouri

  • Study site

    Winter Park, Florida

Other trials in United States

Italy12 sites

  • Study site

    Bari

  • Study site

    Bergamo

  • Study site

    Bologna

  • Study site

    Florence

  • Study site

    Milan

  • Study site

    Naples

  • Study site

    Orbassano

  • Study site

    Pavia

  • Study site

    Reggio Calabria

  • Study site

    Roma

  • Study site

    Varese

  • Study site

    Vicenza

Other trials in Italy

Germany11 sites

  • Study site

    Aachen

  • Study site

    Berlin

  • Study site

    Bonn

  • Study site

    Freiburg im Breisgau

  • Study site

    Hamburg

  • Study site

    Jena

  • Study site

    Magdeburg

  • Study site

    Mannheim

  • Study site

    Minden

  • Study site

    München

  • Study site

    Ulm

Other trials in Germany

Spain9 sites

  • Study site

    A Coruña

  • Study site

    Barcelona

  • Study site

    Las Palmas de Gran Canaria

  • Study site

    Madrid

  • Study site

    Majadahonda

  • Study site

    Málaga

  • Study site

    Pamplona

  • Study site

    Salamanca

  • Study site

    Valencia

Other trials in Spain

France7 sites

  • Study site

    Avignon

  • Study site

    Bayonne

  • Study site

    Brest

  • Study site

    Lille

  • Study site

    Nantes

  • Study site

    Paris

  • Study site

    Vandœuvre-lès-Nancy

Other trials in France

Japan6 sites

  • Study site

    Chiba

  • Study site

    Chuo-city Yamanashi

  • Study site

    Maebashi

  • Study site

    Nagoya-city Aichi

  • Study site

    Osaka

  • Study site

    Tokyo

Other trials in Japan

Belgium4 sites

  • Study site

    Antwerp

  • Study site

    Bruges

  • Study site

    Brussels

  • Study site

    Leuven

Other trials in Belgium

Hungary4 sites

  • Study site

    Budapest

  • Study site

    Kecskemét

  • Study site

    Szeged

  • Study site

    Szombathely

Other trials in Hungary

Australia3 sites

  • Study site

    Brisbane

  • Study site

    Parkville

  • Study site

    Tweed Heads

Other trials in Australia

Canada3 sites

  • Study site

    Hamilton

  • Study site

    Montreal

  • Study site

    Toronto

Other trials in Canada

Turkey (Türkiye)3 sites

  • Study site

    Ankara

  • Study site

    Istanbul

  • Study site

    Izmir

Other trials in Turkey (Türkiye)

United Kingdom3 sites

  • Study site

    Bournemouth

  • Study site

    Cardiff

  • Study site

    London

Other trials in United Kingdom

China2 sites

  • Study site

    Beijing

  • Study site

    Hangzhou

Other trials in China

Netherlands2 sites

  • Study site

    Enschede

  • Study site

    Rotterdam

Other trials in Netherlands

Russia2 sites

  • Study site

    Moscow

  • Study site

    Saint Petersburg

Other trials in Russia

Argentina1 site

  • Study site

    Buenos Aires

Other trials in Argentina

South Korea1 site

  • Study site

    Seoul

Other trials in South Korea

Thailand1 site

  • Study site

    Bangkok

Other trials in Thailand

About this study

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 (The RESPONSE Trial)

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).

Being tested
ruxolitinib tablets, Best Available Therapy (BAT)
Keywords
INCB018424
Medical subject headings
Polycythemia Vera

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ruxolitinib tabletsDrug

    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 (BAT)Other

    Also called BAT could include:, Hydroxyurea, IFN/PEG-IFN, Pipobroman

    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.

Study groups in NCT01243944
Study groupRoleWhat they receive
ruxolitinib tabletsExperimentalStarting 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
Receives: Drug: ruxolitinib tablets
Best Available TherapyOtherBest 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.
Receives: Other: Best Available Therapy (BAT)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: 32 Weeks

Secondary outcomes (12)

  1. 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.

    Measured: 48 Weeks

  2. 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.

    Measured: 32 Weeks

  3. 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.

    Measured: 48 Weeks

  4. 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.

    Measured: 48 Weeks

  5. 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.

    Measured: 48 Weeks

  6. 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.

    Measured: Through study completion, analysis was conducted when all participants had completed the Week 80 visit or discontinued the study

  7. 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.

    Measured: 32 Weeks

  8. 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.

    Measured: 48 Weeks

  9. 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.

    Measured: Through study completion, analysis was conducted when all participants had completed the Week 80 visit or discontinued the study

  10. 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.

    Measured: 256 Weeks

  11. 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.

    Measured: 256 Weeks

  12. 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.

    Measured: 256 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Nov 2010 (estimated)
  2. Study start27 Oct 2010
  3. Primary completion15 Jan 2014
  4. Study completion9 Feb 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
222 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01243944
Sponsor's protocol ID
CINC424B2301
Status last verified
Feb 2019
First submitted
17 Nov 2010
Last updated
6 Mar 2019
Expanded access
Available

Publications

  • Harrison CN, Kiladjian JJ, Hamer-Maansson JE, Naim A, Palandri F, Passamonti F. Ruxolitinib treatment in patients with polycythemia vera reduces JAK2 variant allele frequency and improves symptom burden and hematocrit control. Ther Adv Hematol. 2026 Mar 24;17:20406207261425083. doi: 10.1177/20406207261425083. eCollection 2026.

    PubMed 41890273

  • Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. doi: 10.1016/S2352-3026(19)30207-8. Epub 2020 Jan 23.

    PubMed 31982039

  • Kiladjian JJ, Guglielmelli P, Griesshammer M, Saydam G, Masszi T, Durrant S, Passamonti F, Jones M, Zhen H, Li J, Gadbaw B, Perez Ronco J, Khan M, Verstovsek S. Efficacy and safety of ruxolitinib after and versus interferon use in the RESPONSE studies. Ann Hematol. 2018 Apr;97(4):617-627. doi: 10.1007/s00277-017-3225-1. Epub 2018 Feb 2.

    PubMed 29396713

  • Verstovsek S, Harrison CN, Kiladjian JJ, Miller C, Naim AB, Paranagama DC, Habr D, Vannucchi AM. Markers of iron deficiency in patients with polycythemia vera receiving ruxolitinib or best available therapy. Leuk Res. 2017 May;56:52-59. doi: 10.1016/j.leukres.2017.01.032. Epub 2017 Jan 31.

    PubMed 28193568

  • Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. doi: 10.3324/haematol.2016.143644. Epub 2016 Apr 21.

    PubMed 27102499

  • 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.

    PubMed 25629741

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ruxolitinib tablets and Best Available Therapy (BAT) in people with Polycythemia Vera, run by Incyte Corporation at 102 sites in 18 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 102 sites in United States, Italy, Germany, Spain, France and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Percentage of Participants Achieving a Primary Response at Week 32 (time frame: 32 Weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01243944, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2019.

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