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

Polycythemia Vera Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02218047
• Other study ID #: CONTINUATION-PV
• Secondary ID: 2014-001357-17
• Status: Completed
• Phase: Phase 3
• Start date: November 2014
• Est. completion date: April 29, 2021

Study information

• Verified date: May 2021
• Source: AOP Orphan Pharmaceuticals AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 170
• Est. completion date: April 29, 2021
• Est. primary completion date: April 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Polycythemia
• Polycythemia Vera

Intervention

Drug:
• 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.
• Best available therapy (BAT)
Best available therapy as selected by the investigator

Locations

Country	Name	City	State
Austria	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
Bulgaria	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
Czechia	University Hospital Brno	Brno
Czechia	University Hospital Hradec Kralove	Hradec Kralove
Czechia	University Hospital Kralovske Vinohrady	Prague
Czechia	University Hospital Motol	Prague
France	Institute Paoli-Calmettes	Marseille
France	Hospital Saint-Louis	Paris
France	Clinical Research Center CIC	Poitiers
Germany	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
Hungary	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	Kaposvar
Hungary	University of Szeged, Albert Szent-Gyorgyi Clinical Center, Koranyi fasor 6	Szeged
Poland	University Hospital in Cracow	Krakow
Poland	Independent Public Teaching Hospital No.1 in Lublin	Lublin
Poland	Fryderyk Chopin Provincial Specialized Hospital	Rzeszow
Poland	Nicolaus Copernicus Municipal Specialist Hospital	Torun
Poland	Institute of Hematology and Transfusion Medicine	Warsaw
Romania	Emergency Clinical County Hospital Brasov	Brasov
Romania	Bucharest University Emergency Hospital	Bucharest
Romania	Coltea Clinical Hospital	Bucharest
Russian Federation	Baranov Republican Hospital	Petrozavodsk
Russian Federation	Samara Kalinin Regional Clinical Hospital	Samara
Russian Federation	Komi Republican Oncology Center	Syktyvkar
Russian Federation	Tula Regional Clinical Hospital	Tula
Russian Federation	Yaroslavl Regional Clinical Hospital	Yaroslavl
Slovakia	University Hospital with Outpatient Clinic F.D. Roosevelt	Banska Bystrica
Slovakia	Saint Cyril and Metod University Hospital Bratislava	Bratislava
Spain	Hospital del Mar	Barcelona
Ukraine	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

Sponsors (2)

Lead Sponsor	Collaborator
AOP Orphan Pharmaceuticals AG	PharmaEssentia Corporation (for the U.S.)

Countries where clinical trial is conducted

Austria,  Bulgaria,  Czechia,  France,  Germany,  Hungary,  Poland,  Romania,  Russian Federation,  Slovakia,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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