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

NCT02218047 | Completed Phase 3

• 2 other identifiers: CONTINUATION-PV2014-001357-17
• Study Type: interventional
• Target: 170
• Locations: 12 countries
• Sites: 47

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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).

  3 years

Study Arms (2)

Best available therapy (BAT)

ACTIVE COMPARATOR

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

Drug: Best available therapy (BAT)

Pegylated-Proline-interferon alpha-2b

EXPERIMENTAL

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

Drug: Pegylated-Proline-interferon alpha-2b

Interventions

Pegylated-Proline-interferon alpha-2b 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.

Also known as: AOP2014

Pegylated-Proline-interferon alpha-2b

Best available therapy (BAT) DRUG

Best available therapy as selected by the investigator

Also known as: best available therapy

Best available therapy (BAT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• AOP Orphan Pharmaceuticals AG: lead
• PharmaEssentia Corporation (for the U.S.): collaborator

Study Sites (47)

LKH Graz

Graz, Austria

Location

University Hospital Innsbruck

Innsbruck, Austria

Location

Elisabethinen Hospital Linz

Linz, Austria

Location

Salzburg Regional Hospital

Salzburg, Austria

Location

Hanusch Hospital

Vienna, Austria

Location

Medical University Vienna

Vienna, Austria

Location

Hospital Wels-Grieskirchen

Wels, Austria

Location

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

Plovdiv, Bulgaria

Location

Specialized Hospital for Active Treatment of Hematological Diseases

Sofia, Bulgaria

Location

Multiprofile Hospital for Active Treatment "Sveta Marina", Varna

Varna, Bulgaria

Location

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

Vratsa, Bulgaria

Location

University Hospital Brno

Brno, Czechia

Location

University Hospital Hradec Kralove

Hradec Králové, Czechia

Location

University Hospital Kralovske Vinohrady

Prague, Czechia

Location

University Hospital Motol

Prague, Czechia

Location

Institute Paoli-Calmettes

Marseille, France

Location

Hospital Saint-Louis

Paris, France

Location

Clinical Research Center CIC

Poitiers, France

Location

Aachen University Hospital, Medical Clinic IV

Aachen, Germany

Location

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

Bonn, Germany

Location

University Hospital Carl Gustav Carus, Medical Clinic and Polyclinic I

Dresden, Germany

Location

St Istvan and St Laszlo Hospital of Budapest

Budapest, Hungary

Location

University of Debrecen

Debrecen, Hungary

Location

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

Gyula, Hungary

Location

Kaposi Mor County Teaching Hospital

Kaposvár, Hungary

Location

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

Szeged, Hungary

Location

University Hospital in Cracow

Krakow, Poland

Location

Independent Public Teaching Hospital No.1 in Lublin

Lublin, Poland

Location

Fryderyk Chopin Provincial Specialized Hospital

Rzeszów, Poland

Location

Nicolaus Copernicus Municipal Specialist Hospital

Torun, Poland

Location

Institute of Hematology and Transfusion Medicine

Warsaw, Poland

Location

Emergency Clinical County Hospital Brasov

Brasov, Romania

Location

Bucharest University Emergency Hospital

Bucharest, Romania

Location

Coltea Clinical Hospital

Bucharest, Romania

Location

Baranov Republican Hospital

Petrozavodsk, Russia

Location

Samara Kalinin Regional Clinical Hospital

Samara, Russia

Location

Komi Republican Oncology Center

Syktyvkar, Russia

Location

Tula Regional Clinical Hospital

Tula, Russia

Location

Yaroslavl Regional Clinical Hospital

Yaroslavl, Russia

Location

University Hospital with Outpatient Clinic F.D. Roosevelt

Banská Bystrica, Slovakia

Location

Saint Cyril and Metod University Hospital Bratislava

Bratislava, Slovakia

Location

Hospital del Mar

Barcelona, Spain

Location

Cherkasy Regional Oncology Center, Regional Treatment and Diagnostics Hematology Center

Cherkasy, Ukraine

Location

Dnipropetrovsk City Multispecialty Clinical Hospital #4

Dnipropetrovsk, Ukraine

Location

National Research Center for Radiation Medicine, Institute of Clinical Radiology

Kiev, Ukraine

Location

Institute of Blood Pathology and Transfusion Medicine

Lviv, Ukraine

Location

O.F. Herbachevskyi Regional Clinical Hospital

Zhytomyr, Ukraine

Location

MeSH Terms

Conditions

Polycythemia Vera; Polycythemia; Hematologic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Hemic and Lymphatic Diseases

Study Officials

• Heinz Gisslinger, MD

  Med Uni Wien

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2014
• First Posted: August 15, 2014
• Study Start: November 1, 2014
• Primary Completion: April 29, 2021
• Study Completion: April 29, 2021
• Last Updated: June 1, 2021

Record last verified: 2021-05

Locations

SL (2); HU (5); ES (1); UA (5); PL (5); CZ (4); DE (3); AU (7); FR (3); RO (3); RU (5); BU (4)