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Study to Assess the Self-administration of AOP2014 Using a Pen, Developed for the Treatment of Polycythemia Vera Patients

Phase 3
Completed
Conditions
Polycythemia Vera
Interventions
Drug: Pegylated-Proline-Interferon alpha-2b in a Pre-filled Pen
Registration Number
NCT02523638
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 assess the ease of AOP2014 self-administration using dedicated questionnaires.

* To assess safety and tolerability: adverse events (AEs), laboratory parameters, electrocardiogram (ECG) throughout study.

* To assess maintenance of the blood efficacy parameters Hct (Hematocrit), WBC (white blood cells) and PLTs (platelets) and spleen size (comparing values at Visit P7 vs. values at Visit P1).

* To assess the feasibility of AOP2014 self-administration: defined as the ability of the patients to use the pen as a self-administration tool (ease of handling, safety, tolerability and efficacy).

Detailed Description

This is a Phase III, single-arm study performed in patients who completed the AOP2014 arm of the PROUD-PV study or are currently participating in the CONTINUATION-PV study. After signing the informed consent form (ICF), approximately 30 patients will be enrolled consecutively into the study at participating sites according to the inclusion and exclusion criteria.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
Inclusion Criteria
  1. Patients who either completed the 12 months AOP2014 treatment arm of the PROUD-PV study, or are currently participating in the CONTINUATION-PV, and at the "EoT visit" (End of treatment visit) of the PROUD-PV study or two weeks after the last assessment visit of the CONTINUATION-PV study, fulfill at least one of the following criteria:

    • Normalization of at least two out of three main blood parameters (Hct (Hematocrit), PLTs (Platelets) and WBCs (white blood cells) if these parameters were moderately increased (Hct<50%, WBCs<20 x 109/L, PLTs<600 x 109/L) at baseline visit 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 visit of the PROUD-PV study, OR
    • Normalization of spleen size, if spleen was enlarged at baseline visit 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 (Januskinase 2) allelic burden).
  2. Signed written ICF.

Exclusion Criteria

Withdrawal criteria, as specified in the PROUD-PV and CONTINUATION-PV studies, 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 (Hospital Anxiety and Depression Scale) score of 11 or higher on either or both of the subscales, and /or development or worsening of 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Pegylated- Proline-Interferon alpha-2bPegylated-Proline-Interferon alpha-2b in a Pre-filled PenPegylated-Proline-Interferon alpha-2b in a Pre-filled Pen single arm
Primary Outcome Measures
NameTimeMethod
To evaluate ease of self-administration of AOP20143 months

To evaluate ease of self-administration of AOP2014 as assessed by staff and patients using dedicated questionnaires, using rates of full success and failure rates (defined in the statistics section of the synopsis).

Secondary Outcome Measures
NameTimeMethod
number of phlebotomies3 months

biweekly

spleen size3 months

locally, Sonography will be used for measuring the spleen size (length). at Visit 1 and at the End of the study (week 12)

disease related symptoms3 months

biweekly, using dedicated questionnaires

protocol-specific adverse events of special interest3 months

biweekly, using dedicated questionnaires

Adverse Event3 month

biweekly, using dedicated questionnaires

Disease response3 months

The main efficacy evaluation criterion will be disease response defined as:

• WBCs (White blood cells)\< 10 x 109/L. The hematological parameters will be measured by the local laboratories at clinical sites.

blood parameters3 months

first biweekly than monthly

The main efficacy evaluation criterion will be disease response defined as:

• PLTs\< 400 x 109/L. The hematological parameters will be measured by the local laboratories at clinical sites.

Trial Locations

Locations (35)

Dnipropetrovsk City Multispecialty Clinical Hospital #4

🇺🇦

Dnipropetrovsk, Ukraine

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

🇭🇺

Szeged, Hungary

O.F. Herbachevskyi Regional Clinical Hospital

🇺🇦

Zhytomyr, Ukraine

University Hospital Innsbruck

🇦🇹

Innsbruck, Austria

Medical University Vienna

🇦🇹

Vienna, Austria

Institute of Hematology and Transfusion Medicine

🇵🇱

Warsaw, Poland

Saint Cyril and Metod University Hospital Bratislava

🇸🇰

Bratislava, Slovakia

Cherkasy Regional Oncology Center, Regional Treatment and Diagnostics Hematology Center

🇺🇦

Cherkasy, Ukraine

Institute of Blood Pathology and Transfusion Medicine

🇺🇦

Lviv, Ukraine

Nicolaus Copernicus Municipal Specialist Hospital

🇵🇱

Torun, Poland

Elisabethinen Hospital Linz

🇦🇹

Linz, Austria

Salzburg Regional Hospital

🇦🇹

Salzburg, Austria

Independent Public Teaching Hospital No.1 in Lublin

🇵🇱

Lublin, Poland

University Hospital with Outpatient Clinic F.D. Roosevelt

🇸🇰

Banska Bystrica, Slovakia

Kaposi Mor County Teaching Hospital

🇭🇺

Kaposvar, Hungary

Institute of Hematology and Blood Transfusion

🇨🇿

Prague, Czech Republic

Andrzej Mielecki Independent Public Clinical Hospital of Medical University of Silesia in Katowice

🇵🇱

Katowice, Poland

University of Debrecen

🇭🇺

Debrecen, Hungary

Hanusch Hospital

🇦🇹

Vienna, Austria

LKH Graz

🇦🇹

Graz, Austria

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

🇧🇬

Vratsa, Bulgaria

Specialized Hospital for Active Treatment of Hematological Diseases

🇧🇬

Sofia, Bulgaria

Hospital Wels-Grieskirchen

🇦🇹

Wels, Austria

University Hospital Hradec Kralove

🇨🇿

Hradec Kralove, Czech Republic

University Hospital Kralovske Vinohrady

🇨🇿

Prague, Czech Republic

University Hospital Motol

🇨🇿

Prague, Czech Republic

Institute Paoli-Calmettes

🇫🇷

Marseilles, France

Hospital Saint-Louis

🇫🇷

Paris, France

St Istvan and St Laszlo Hospital of Budapest

🇭🇺

Budapest, Hungary

Clinical Research Center CIC

🇫🇷

Poitiers, France

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

🇭🇺

Gyula, Hungary

University Hospital Brno

🇨🇿

Brno, Czech Republic

University Hospital in Cracow

🇵🇱

Krakow, Poland

Fryderyk Chopin Provincial Specialized Hospital

🇵🇱

Rzeszow, Poland

National Research Center for Radiation Medicine, Institute of Clinical Radiology

🇺🇦

Kiev, Ukraine

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