Clinical trial NCT02218047: AOP2014 vs. BAT in Patients With Polycythemia Vera Who Previously Participated in the PROUD-PV Study.
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
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: AOP Orphan Pharmaceuticals AG
Sponsor class: INDUSTRY
Collaborators: name: PharmaEssentia Corporation (for the U.S.)
First posted: 2014-08-15
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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).

Primary outcomes:
measure: Disease response at quarterly assessment visits
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Graz
country: Austria
facility: LKH Graz
city: Innsbruck
country: Austria
facility: University Hospital Innsbruck
city: Linz
country: Austria
facility: Elisabethinen Hospital Linz
city: Salzburg
country: Austria
facility: Salzburg Regional Hospital
city: Vienna
country: Austria
facility: Hanusch Hospital
city: Vienna
country: Austria
facility: Medical University Vienna
city: Wels
country: Austria
facility: Hospital Wels-Grieskirchen
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Hematological Diseases
city: Varna
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "Sveta Marina", Varna
city: Vratsa
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Hristo Botev, Vratsa, First Department of Internal Medicine
city: Brno
country: Czechia
facility: University Hospital Brno
city: Hradec Kralove
country: Czechia
facility: University Hospital Hradec Kralove
city: Prague
country: Czechia
facility: University Hospital Kralovske Vinohrady
city: Prague
country: Czechia
facility: University Hospital Motol
city: Marseille
country: France
facility: Institute Paoli-Calmettes
city: Paris
country: France
facility: Hospital Saint-Louis
city: Poitiers
country: France
facility: Clinical Research Center CIC
city: Aachen
country: Germany
facility: Aachen University Hospital, Medical Clinic IV
city: Bonn
country: Germany
facility: University Hospital Bonn, Center for Internal Medicine, Medical Clinic and Outpatient Clinic III
city: Dresden
country: Germany
facility: University Hospital Carl Gustav Carus, Medical Clinic and Polyclinic I
city: Budapest
country: Hungary
facility: St Istvan and St Laszlo Hospital of Budapest
city: Debrecen
country: Hungary
facility: University of Debrecen
city: Gyula
country: Hungary
facility: Bekes County Pandy Kalman Hospital, 1st Department of Medicine, Hematology
city: Kaposvar
country: Hungary
facility: Kaposi Mor County Teaching Hospital
city: Szeged
country: Hungary
facility: University of Szeged, Albert Szent-Gyorgyi Clinical Center, Koranyi fasor 6
city: Krakow
country: Poland
facility: University Hospital in Cracow
city: Lublin
country: Poland
facility: Independent Public Teaching Hospital No.1 in Lublin
city: Rzeszow
country: Poland
facility: Fryderyk Chopin Provincial Specialized Hospital
city: Torun
country: Poland
facility: Nicolaus Copernicus Municipal Specialist Hospital
city: Warsaw
country: Poland
facility: Institute of Hematology and Transfusion Medicine
city: Brasov
country: Romania
facility: Emergency Clinical County Hospital Brasov
city: Bucharest
country: Romania
facility: Bucharest University Emergency Hospital
city: Bucharest
country: Romania
facility: Coltea Clinical Hospital
city: Petrozavodsk
country: Russian Federation
facility: Baranov Republican Hospital
city: Samara
country: Russian Federation
facility: Samara Kalinin Regional Clinical Hospital
city: Syktyvkar
country: Russian Federation
facility: Komi Republican Oncology Center
city: Tula
country: Russian Federation
facility: Tula Regional Clinical Hospital
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl Regional Clinical Hospital
city: Banska Bystrica
country: Slovakia
facility: University Hospital with Outpatient Clinic F.D. Roosevelt
city: Bratislava
country: Slovakia
facility: Saint Cyril and Metod University Hospital Bratislava
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Cherkasy
country: Ukraine
facility: Cherkasy Regional Oncology Center, Regional Treatment and Diagnostics Hematology Center
city: Dnipropetrovsk
country: Ukraine
facility: Dnipropetrovsk City Multispecialty Clinical Hospital #4
city: Kiev
country: Ukraine
facility: National Research Center for Radiation Medicine, Institute of Clinical Radiology
city: Lviv
country: Ukraine
facility: Institute of Blood Pathology and Transfusion Medicine
city: Zhytomyr
country: Ukraine
facility: O.F. Herbachevskyi Regional Clinical Hospital
Study officials:
affiliation: Med Uni Wien
name: Heinz Gisslinger, MD
role: PRINCIPAL_INVESTIGATOR
References: