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AOP2014 vs. BAT in Patients With Polycythemia Vera Who Previously Participated in the PROUD-PV Study. (CONTI-PV)

Primary Purpose

Polycythemia Vera

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Pegylated-Proline-interferon alpha-2b
Best available therapy (BAT)
Sponsored by
AOP Orphan Pharmaceuticals AG
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Polycythemia Vera focused on measuring Pegylated-Proline-interferon alpha-2b (AOP2014), Polycythemia Vera, PROUD-PV, CONTINUATION-PV, AOP Orphan, Polycythemia, Hematologic Diseases, Myeloproliferative Disorders, Bone Marrow Diseases, Interferon-alpha, Peginterferon alfa-2b

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients who completed the 12 months AOP2014 treatment arm of the PROUD-PV study and at the "end-of-treatment visit" (EoT) of the PROUD-PV study who fulfill at least one of the following criteria:

    • normalization of at least two out of three main blood parameters (Hct, PLTs and WBCs) if these parameters were moderately increased (Hct<50%, WBC<20 x 109/L, PLTs<600 x 109/L) at baseline of the PROUD-PV study, OR
    • >35% decrease of at least two out of three main blood parameters (Hct, PLTs and WBCs) if these parameters were massively increased (Hct>50%, WBCs>20 x 109/L, PLTs>600 x 109/L), at baseline of the PROUD-PV study, OR
    • normalization of spleen size, if spleen was enlarged at baseline of the PROUD-PV study, OR
    • otherwise a clear, medically verified benefit from treatment with AOP2014 (e.g. normalization of disease-related micro-vasculatory symptoms, substantial decrease of JAK2 allelic burden).
  2. Signed written ICF.

Exclusion criteria:

Withdrawal criteria, as specified in the PROUD-PV study, which mandate treatment discontinuation:

  1. Non-recovery from the AOP2014 related toxicities to the grade (usually, Grade I) which allows continuation of the treatment.
  2. HADS score of 11 or higher on either or both of the subscales, and /or development or worsening of the clinically significant depression or suicidal thoughts.
  3. Progressive and clinically significant increase of liver enzyme levels despite dose reduction, or if such increase is accompanied by increased bilirubin level, any signs or symptoms of a clinically significant autoimmune disease.
  4. Clinically significant development of a new ophthalmologic disorder, or worsening of a pre-existing one, during the study.
  5. Loss of efficacy of AOP2014 or any comparable situation where no further benefits of treatment continuation are expected by the investigator.

The main efficacy evaluation criterion will be disease response defined as Hct<45% without phlebotomy (at least 3 months since the last phlebotomy), PLTs<400 x 109/L, WBCs<10 x 109/L, and normal spleen size.

The main efficacy endpoint will be the maintenance rate of disease response at assessment visits (every three months).

Sites / Locations

  • LKH Graz
  • University Hospital Innsbruck
  • Elisabethinen Hospital Linz
  • Salzburg Regional Hospital
  • Hanusch Hospital
  • Medical University Vienna
  • Hospital Wels-Grieskirchen
  • University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv
  • Specialized Hospital for Active Treatment of Hematological Diseases
  • Multiprofile Hospital for Active Treatment "Sveta Marina", Varna
  • Multiprofile Hospital for Active Treatment - Hristo Botev, Vratsa, First Department of Internal Medicine
  • University Hospital Brno
  • University Hospital Hradec Kralove
  • University Hospital Kralovske Vinohrady
  • University Hospital Motol
  • Institute Paoli-Calmettes
  • Hospital Saint-Louis
  • Clinical Research Center CIC
  • Aachen University Hospital, Medical Clinic IV
  • University Hospital Bonn, Center for Internal Medicine, Medical Clinic and Outpatient Clinic III
  • University Hospital Carl Gustav Carus, Medical Clinic and Polyclinic I
  • St Istvan and St Laszlo Hospital of Budapest
  • University of Debrecen
  • Bekes County Pandy Kalman Hospital, 1st Department of Medicine, Hematology
  • Kaposi Mor County Teaching Hospital
  • University of Szeged, Albert Szent-Gyorgyi Clinical Center, Koranyi fasor 6
  • University Hospital in Cracow
  • Independent Public Teaching Hospital No.1 in Lublin
  • Fryderyk Chopin Provincial Specialized Hospital
  • Nicolaus Copernicus Municipal Specialist Hospital
  • Institute of Hematology and Transfusion Medicine
  • Emergency Clinical County Hospital Brasov
  • Bucharest University Emergency Hospital
  • Coltea Clinical Hospital
  • Baranov Republican Hospital
  • Samara Kalinin Regional Clinical Hospital
  • Komi Republican Oncology Center
  • Tula Regional Clinical Hospital
  • Yaroslavl Regional Clinical Hospital
  • University Hospital with Outpatient Clinic F.D. Roosevelt
  • Saint Cyril and Metod University Hospital Bratislava
  • Hospital del Mar
  • Cherkasy Regional Oncology Center, Regional Treatment and Diagnostics Hematology Center
  • Dnipropetrovsk City Multispecialty Clinical Hospital #4
  • National Research Center for Radiation Medicine, Institute of Clinical Radiology
  • Institute of Blood Pathology and Transfusion Medicine
  • O.F. Herbachevskyi Regional Clinical Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Best available therapy (BAT)

Pegylated-Proline-interferon alpha-2b

Arm Description

Best available therapy, as chosen by the investigator for patients who had been on HU in the 1 Year PROUD-PV study

AOP2014 for those patients who had been on AOP2014 in the PROUD-PV study

Outcomes

Primary Outcome Measures

Disease response at quarterly assessment visits
The primary efficacy endpoint will be the rate of disease response at assessment visits (every 3 months). The co-primary efficacy evaluation criterion will be (1) disease response defined as hematologic response: Hct<45% without phlebotomy (at least 3 months since the last phlebotomy), PLTs<400 x 109/L, WBCs<10 x 109/L, and normal spleen size, and (2) disease response defined as hematologic response (Hct<45% without phlebotomy (at least 3 months since the last phlebotomy), PLTs<400 x 109/L, WBCs<10 x 109/L), resolution and/or clinically improvement of disease-related signs (clinical significant splenomegaly) and disease-related symptoms (microvascular disturbances, pruritus, headache).

Secondary Outcome Measures

Full Information

First Posted
August 14, 2014
Last Updated
May 27, 2021
Sponsor
AOP Orphan Pharmaceuticals AG
Collaborators
PharmaEssentia Corporation (for the U.S.)
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1. Study Identification

Unique Protocol Identification Number
NCT02218047
Brief Title
AOP2014 vs. BAT in Patients With Polycythemia Vera Who Previously Participated in the PROUD-PV Study.
Acronym
CONTI-PV
Official Title
An Open-label, Multicenter, Phase IIIb Study Assessing the Long-term Efficacy and Safety of AOP2014 and Standard First Line Treatment (BAT) in Patients With Polycythemia Vera Who Previously Participated in the PROUD-PV Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
November 2014 (Actual)
Primary Completion Date
April 29, 2021 (Actual)
Study Completion Date
April 29, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AOP Orphan Pharmaceuticals AG
Collaborators
PharmaEssentia Corporation (for the U.S.)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Polycythemia Vera (PV) is a disease of bone marrow stem cells that manifests in a drastic increase of red blood cells and frequently also of white blood cells. The "thickening" of the blood in relation with a modified function of the cells has several consequences like increased blood pressure, pruritus of the skin, fatigue, disturbed blood circulation in the brain as well as fingers and toes and an increased risk of arterial and venous thrombosis (thrombosis is the formation of a blood clot in a vessel); like stroke, cardiac infarction, deep vein thrombosis in the legs. In case of a strong increase of platelets there is an additional risk of bleedings. As the disease progresses the size of spleen and liver increased in most cases and the bone marrow shows signs of fibrosis. In some cases of PV a progression at a later time point to a leukemia (increased formation of white blood cells) can occur. The aim of this study is to show that the study drug AOP2014 (pegylated proline interferon alpha-2b) has the long term efficacy and safety in controlling the disease. A comparison arm is receiving best available therapy as selected by the investigator. Response to the treatment is measured by several blood parameters as well as size of the spleen. Interferon-alpha has been shown to be effective in controlling the blood parameters by immunologically influencing the blood building cells. This can lead to a suppression of the disease-causing stem cells and help healthy stem cells to proliferate. Through this mechanism it is possible that Interferon-alpha can avoid long-term damaging effects of the disease.
Detailed Description
This is a Phase III, parallel-arm, open-label continuation of the PROUD-PV study performed in adults diagnosed with Polycythemia Vera (PV). Patients who received AOP2014 in the primary study, PROUD-PV will continue on AOP2014, patients who received HU in the PROUD-PV study will receive best available therapy as selected by the investigator. Only patients who completed PROUD-PV including the end of study visit will be enrolled into this continuation study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycythemia Vera
Keywords
Pegylated-Proline-interferon alpha-2b (AOP2014), Polycythemia Vera, PROUD-PV, CONTINUATION-PV, AOP Orphan, Polycythemia, Hematologic Diseases, Myeloproliferative Disorders, Bone Marrow Diseases, Interferon-alpha, Peginterferon alfa-2b

7. Study Design

Primary Purpose
Other
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
170 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Best available therapy (BAT)
Arm Type
Active Comparator
Arm Description
Best available therapy, as chosen by the investigator for patients who had been on HU in the 1 Year PROUD-PV study
Arm Title
Pegylated-Proline-interferon alpha-2b
Arm Type
Experimental
Arm Description
AOP2014 for those patients who had been on AOP2014 in the PROUD-PV study
Intervention Type
Drug
Intervention Name(s)
Pegylated-Proline-interferon alpha-2b
Other Intervention Name(s)
AOP2014
Intervention Description
Subjects will continue to receive the dosage which delivers the optimal disease response (hematocrit [Hct]<45%, platelets [PLTs]<400 x 109/L and leukocytes [WBCs]<10 x 109/L), as determined in the PROUD-PV study, preferably at the level of target blood values.
Intervention Type
Drug
Intervention Name(s)
Best available therapy (BAT)
Other Intervention Name(s)
best available therapy
Intervention Description
Best available therapy as selected by the investigator
Primary Outcome Measure Information:
Title
Disease response at quarterly assessment visits
Description
The primary efficacy endpoint will be the rate of disease response at assessment visits (every 3 months). The co-primary efficacy evaluation criterion will be (1) disease response defined as hematologic response: Hct<45% without phlebotomy (at least 3 months since the last phlebotomy), PLTs<400 x 109/L, WBCs<10 x 109/L, and normal spleen size, and (2) disease response defined as hematologic response (Hct<45% without phlebotomy (at least 3 months since the last phlebotomy), PLTs<400 x 109/L, WBCs<10 x 109/L), resolution and/or clinically improvement of disease-related signs (clinical significant splenomegaly) and disease-related symptoms (microvascular disturbances, pruritus, headache).
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients who completed the 12 months AOP2014 treatment arm of the PROUD-PV study and at the "end-of-treatment visit" (EoT) of the PROUD-PV study who fulfill at least one of the following criteria: normalization of at least two out of three main blood parameters (Hct, PLTs and WBCs) if these parameters were moderately increased (Hct<50%, WBC<20 x 109/L, PLTs<600 x 109/L) at baseline of the PROUD-PV study, OR >35% decrease of at least two out of three main blood parameters (Hct, PLTs and WBCs) if these parameters were massively increased (Hct>50%, WBCs>20 x 109/L, PLTs>600 x 109/L), at baseline of the PROUD-PV study, OR normalization of spleen size, if spleen was enlarged at baseline of the PROUD-PV study, OR otherwise a clear, medically verified benefit from treatment with AOP2014 (e.g. normalization of disease-related micro-vasculatory symptoms, substantial decrease of JAK2 allelic burden). Signed written ICF. Exclusion criteria: Withdrawal criteria, as specified in the PROUD-PV study, which mandate treatment discontinuation: Non-recovery from the AOP2014 related toxicities to the grade (usually, Grade I) which allows continuation of the treatment. HADS score of 11 or higher on either or both of the subscales, and /or development or worsening of the clinically significant depression or suicidal thoughts. Progressive and clinically significant increase of liver enzyme levels despite dose reduction, or if such increase is accompanied by increased bilirubin level, any signs or symptoms of a clinically significant autoimmune disease. Clinically significant development of a new ophthalmologic disorder, or worsening of a pre-existing one, during the study. Loss of efficacy of AOP2014 or any comparable situation where no further benefits of treatment continuation are expected by the investigator. The main efficacy evaluation criterion will be disease response defined as Hct<45% without phlebotomy (at least 3 months since the last phlebotomy), PLTs<400 x 109/L, WBCs<10 x 109/L, and normal spleen size. The main efficacy endpoint will be the maintenance rate of disease response at assessment visits (every three months).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Heinz Gisslinger, MD
Organizational Affiliation
Med Uni Wien
Official's Role
Principal Investigator
Facility Information:
Facility Name
LKH Graz
City
Graz
Country
Austria
Facility Name
University Hospital Innsbruck
City
Innsbruck
Country
Austria
Facility Name
Elisabethinen Hospital Linz
City
Linz
Country
Austria
Facility Name
Salzburg Regional Hospital
City
Salzburg
Country
Austria
Facility Name
Hanusch Hospital
City
Vienna
Country
Austria
Facility Name
Medical University Vienna
City
Vienna
Country
Austria
Facility Name
Hospital Wels-Grieskirchen
City
Wels
Country
Austria
Facility Name
University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv
City
Plovdiv
Country
Bulgaria
Facility Name
Specialized Hospital for Active Treatment of Hematological Diseases
City
Sofia
Country
Bulgaria
Facility Name
Multiprofile Hospital for Active Treatment "Sveta Marina", Varna
City
Varna
Country
Bulgaria
Facility Name
Multiprofile Hospital for Active Treatment - Hristo Botev, Vratsa, First Department of Internal Medicine
City
Vratsa
Country
Bulgaria
Facility Name
University Hospital Brno
City
Brno
Country
Czechia
Facility Name
University Hospital Hradec Kralove
City
Hradec Kralove
Country
Czechia
Facility Name
University Hospital Kralovske Vinohrady
City
Prague
Country
Czechia
Facility Name
University Hospital Motol
City
Prague
Country
Czechia
Facility Name
Institute Paoli-Calmettes
City
Marseille
Country
France
Facility Name
Hospital Saint-Louis
City
Paris
Country
France
Facility Name
Clinical Research Center CIC
City
Poitiers
Country
France
Facility Name
Aachen University Hospital, Medical Clinic IV
City
Aachen
Country
Germany
Facility Name
University Hospital Bonn, Center for Internal Medicine, Medical Clinic and Outpatient Clinic III
City
Bonn
Country
Germany
Facility Name
University Hospital Carl Gustav Carus, Medical Clinic and Polyclinic I
City
Dresden
Country
Germany
Facility Name
St Istvan and St Laszlo Hospital of Budapest
City
Budapest
Country
Hungary
Facility Name
University of Debrecen
City
Debrecen
Country
Hungary
Facility Name
Bekes County Pandy Kalman Hospital, 1st Department of Medicine, Hematology
City
Gyula
Country
Hungary
Facility Name
Kaposi Mor County Teaching Hospital
City
Kaposvar
Country
Hungary
Facility Name
University of Szeged, Albert Szent-Gyorgyi Clinical Center, Koranyi fasor 6
City
Szeged
Country
Hungary
Facility Name
University Hospital in Cracow
City
Krakow
Country
Poland
Facility Name
Independent Public Teaching Hospital No.1 in Lublin
City
Lublin
Country
Poland
Facility Name
Fryderyk Chopin Provincial Specialized Hospital
City
Rzeszow
Country
Poland
Facility Name
Nicolaus Copernicus Municipal Specialist Hospital
City
Torun
Country
Poland
Facility Name
Institute of Hematology and Transfusion Medicine
City
Warsaw
Country
Poland
Facility Name
Emergency Clinical County Hospital Brasov
City
Brasov
Country
Romania
Facility Name
Bucharest University Emergency Hospital
City
Bucharest
Country
Romania
Facility Name
Coltea Clinical Hospital
City
Bucharest
Country
Romania
Facility Name
Baranov Republican Hospital
City
Petrozavodsk
Country
Russian Federation
Facility Name
Samara Kalinin Regional Clinical Hospital
City
Samara
Country
Russian Federation
Facility Name
Komi Republican Oncology Center
City
Syktyvkar
Country
Russian Federation
Facility Name
Tula Regional Clinical Hospital
City
Tula
Country
Russian Federation
Facility Name
Yaroslavl Regional Clinical Hospital
City
Yaroslavl
Country
Russian Federation
Facility Name
University Hospital with Outpatient Clinic F.D. Roosevelt
City
Banska Bystrica
Country
Slovakia
Facility Name
Saint Cyril and Metod University Hospital Bratislava
City
Bratislava
Country
Slovakia
Facility Name
Hospital del Mar
City
Barcelona
Country
Spain
Facility Name
Cherkasy Regional Oncology Center, Regional Treatment and Diagnostics Hematology Center
City
Cherkasy
Country
Ukraine
Facility Name
Dnipropetrovsk City Multispecialty Clinical Hospital #4
City
Dnipropetrovsk
Country
Ukraine
Facility Name
National Research Center for Radiation Medicine, Institute of Clinical Radiology
City
Kiev
Country
Ukraine
Facility Name
Institute of Blood Pathology and Transfusion Medicine
City
Lviv
Country
Ukraine
Facility Name
O.F. Herbachevskyi Regional Clinical Hospital
City
Zhytomyr
Country
Ukraine

12. IPD Sharing Statement

Learn more about this trial

AOP2014 vs. BAT in Patients With Polycythemia Vera Who Previously Participated in the PROUD-PV Study.

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