AOP2014 vs. BAT in Patients With Polycythemia Vera Who Previously Participated in the PROUD-PV Study.
- Conditions
- Polycythemia Vera
- Interventions
- Drug: Best available therapy (BAT)Drug: Pegylated-Proline-interferon alpha-2b
- Registration Number
- NCT02218047
- Lead Sponsor
- AOP Orphan Pharmaceuticals AG
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 170
-
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).
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Best available therapy (BAT) 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 Pegylated-Proline-interferon alpha-2b Pegylated-Proline-interferon alpha-2b AOP2014 for those patients who had been on AOP2014 in the PROUD-PV study
- Primary Outcome Measures
Name Time Method Disease response at quarterly assessment visits 3 years 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
Name Time Method
Trial Locations
- Locations (47)
University Hospital with Outpatient Clinic F.D. Roosevelt
🇸🇰Banska Bystrica, Slovakia
Nicolaus Copernicus Municipal Specialist Hospital
🇵🇱Torun, Poland
Bucharest University Emergency Hospital
🇷🇴Bucharest, Romania
Elisabethinen Hospital Linz
🇦🇹Linz, Austria
University Hospital Innsbruck
🇦🇹Innsbruck, Austria
Specialized Hospital for Active Treatment of Hematological Diseases
🇧🇬Sofia, Bulgaria
LKH Graz
🇦🇹Graz, Austria
Hanusch Hospital
🇦🇹Vienna, Austria
Medical University Vienna
🇦🇹Vienna, Austria
Hospital Wels-Grieskirchen
🇦🇹Wels, Austria
University Hospital in Cracow
🇵🇱Krakow, Poland
Fryderyk Chopin Provincial Specialized Hospital
🇵🇱Rzeszow, Poland
University Hospital Carl Gustav Carus, Medical Clinic and Polyclinic I
🇩🇪Dresden, Germany
University of Szeged, Albert Szent-Gyorgyi Clinical Center, Koranyi fasor 6
🇭🇺Szeged, Hungary
Independent Public Teaching Hospital No.1 in Lublin
🇵🇱Lublin, Poland
University of Debrecen
🇭🇺Debrecen, Hungary
Kaposi Mor County Teaching Hospital
🇭🇺Kaposvar, Hungary
St Istvan and St Laszlo Hospital of Budapest
🇭🇺Budapest, Hungary
University Hospital Brno
🇨🇿Brno, Czechia
Bekes County Pandy Kalman Hospital, 1st Department of Medicine, Hematology
🇭🇺Gyula, Hungary
Samara Kalinin Regional Clinical Hospital
🇷🇺Samara, Russian Federation
Komi Republican Oncology Center
🇷🇺Syktyvkar, Russian Federation
Emergency Clinical County Hospital Brasov
🇷🇴Brasov, Romania
Tula Regional Clinical Hospital
🇷🇺Tula, Russian Federation
Yaroslavl Regional Clinical Hospital
🇷🇺Yaroslavl, Russian Federation
University Hospital Hradec Kralove
🇨🇿Hradec Kralove, Czechia
University Hospital Kralovske Vinohrady
🇨🇿Prague, Czechia
Aachen University Hospital, Medical Clinic IV
🇩🇪Aachen, Germany
Institute of Hematology and Transfusion Medicine
🇵🇱Warsaw, Poland
Coltea Clinical Hospital
🇷🇴Bucharest, Romania
Baranov Republican Hospital
🇷🇺Petrozavodsk, Russian Federation
Saint Cyril and Metod University Hospital Bratislava
🇸🇰Bratislava, Slovakia
Institute of Blood Pathology and Transfusion Medicine
🇺🇦Lviv, Ukraine
Hospital del Mar
🇪🇸Barcelona, Spain
O.F. Herbachevskyi Regional Clinical Hospital
🇺🇦Zhytomyr, Ukraine
Salzburg Regional Hospital
🇦🇹Salzburg, Austria
Multiprofile Hospital for Active Treatment "Sveta Marina", Varna
🇧🇬Varna, Bulgaria
University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv
🇧🇬Plovdiv, Bulgaria
Multiprofile Hospital for Active Treatment - Hristo Botev, Vratsa, First Department of Internal Medicine
🇧🇬Vratsa, Bulgaria
Institute Paoli-Calmettes
🇫🇷Marseille, France
University Hospital Motol
🇨🇿Prague, Czechia
Hospital Saint-Louis
🇫🇷Paris, France
Clinical Research Center CIC
🇫🇷Poitiers, France
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
University Hospital Bonn, Center for Internal Medicine, Medical Clinic and Outpatient Clinic III
🇩🇪Bonn, Germany