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

NCT ID: NCT02218047

Last Updated: 2021-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2021-04-29

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.

Conditions

Polycythemia Vera

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Best available therapy (BAT)

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

Group Type: ACTIVE_COMPARATOR

Best available therapy (BAT)

Intervention Type: DRUG

Best available therapy as selected by the investigator

Pegylated-Proline-interferon alpha-2b

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

Group Type: EXPERIMENTAL

Pegylated-Proline-interferon alpha-2b

Intervention Type: DRUG

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.

Interventions

Pegylated-Proline-interferon alpha-2b

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

Best available therapy (BAT)

Best available therapy as selected by the investigator

Intervention Type: DRUG

Other Intervention Names

AOP2014; best available therapy

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PharmaEssentia Corporation (for the U.S.)

UNKNOWN

Sponsor Role: collaborator

AOP Orphan Pharmaceuticals AG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Heinz Gisslinger, MD

Role: PRINCIPAL_INVESTIGATOR

Med Uni Wien

Locations

LKH Graz

Graz, , Austria

University Hospital Innsbruck

Innsbruck, , Austria

Elisabethinen Hospital Linz

Linz, , Austria

Salzburg Regional Hospital

Salzburg, , Austria

Hanusch Hospital

Vienna, , Austria

Medical University Vienna

Vienna, , Austria

Hospital Wels-Grieskirchen

Wels, , Austria

University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv

Plovdiv, , Bulgaria

Specialized Hospital for Active Treatment of Hematological Diseases

Sofia, , Bulgaria

Multiprofile Hospital for Active Treatment "Sveta Marina", Varna

Varna, , Bulgaria

Multiprofile Hospital for Active Treatment - Hristo Botev, Vratsa, First Department of Internal Medicine

Vratsa, , Bulgaria

University Hospital Brno

Brno, , Czechia

University Hospital Hradec Kralove

Hradec Králové, , Czechia

University Hospital Kralovske Vinohrady

Prague, , Czechia

University Hospital Motol

Prague, , Czechia

Institute Paoli-Calmettes

Marseille, , France

Hospital Saint-Louis

Paris, , France

Clinical Research Center CIC

Poitiers, , France

Aachen University Hospital, Medical Clinic IV

Aachen, , Germany

University Hospital Bonn, Center for Internal Medicine, Medical Clinic and Outpatient Clinic III

Bonn, , Germany

University Hospital Carl Gustav Carus, Medical Clinic and Polyclinic I

Dresden, , Germany

St Istvan and St Laszlo Hospital of Budapest

Budapest, , Hungary

University of Debrecen

Debrecen, , Hungary

Bekes County Pandy Kalman Hospital, 1st Department of Medicine, Hematology

Gyula, , Hungary

Kaposi Mor County Teaching Hospital

Kaposvár, , Hungary

University of Szeged, Albert Szent-Gyorgyi Clinical Center, Koranyi fasor 6

Szeged, , Hungary

University Hospital in Cracow

Krakow, , Poland

Independent Public Teaching Hospital No.1 in Lublin

Lublin, , Poland

Fryderyk Chopin Provincial Specialized Hospital

Rzeszów, , Poland

Nicolaus Copernicus Municipal Specialist Hospital

Torun, , Poland

Institute of Hematology and Transfusion Medicine

Warsaw, , Poland

Emergency Clinical County Hospital Brasov

Brasov, , Romania

Bucharest University Emergency Hospital

Bucharest, , Romania

Coltea Clinical Hospital

Bucharest, , Romania

Baranov Republican Hospital

Petrozavodsk, , Russia

Samara Kalinin Regional Clinical Hospital

Samara, , Russia

Komi Republican Oncology Center

Syktyvkar, , Russia

Tula Regional Clinical Hospital

Tula, , Russia

Yaroslavl Regional Clinical Hospital

Yaroslavl, , Russia

University Hospital with Outpatient Clinic F.D. Roosevelt

Banská Bystrica, , Slovakia

Saint Cyril and Metod University Hospital Bratislava

Bratislava, , Slovakia

Hospital del Mar

Barcelona, , Spain

Cherkasy Regional Oncology Center, Regional Treatment and Diagnostics Hematology Center

Cherkasy, , Ukraine

Dnipropetrovsk City Multispecialty Clinical Hospital #4

Dnipropetrovsk, , Ukraine

National Research Center for Radiation Medicine, Institute of Clinical Radiology

Kiev, , Ukraine

Institute of Blood Pathology and Transfusion Medicine

Lviv, , Ukraine

O.F. Herbachevskyi Regional Clinical Hospital

Zhytomyr, , Ukraine

Countries

Austria; Bulgaria; Czechia; France; Germany; Hungary; Poland; Romania; Russia; Slovakia; Spain; Ukraine

Other Identifiers

2014-001357-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CONTINUATION-PV

Identifier Type: -

Identifier Source: org_study_id