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

An Open-label, Single Arm, Phase III Study to Assess the Self-administration of AOP2014 Using a Pre-filled Pen, Developed for the Treatment of Polycythemia Vera Patients

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).

Study Overview

• Status: Completed
• Conditions: Polycythemia Vera
• Intervention / Treatment: Drug: Pegylated-Proline-Interferon alpha-2b in a Pre-filled Pen

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
    • LKH Graz
  • Innsbruck, Austria
    • University Hospital Innsbruck
  • Linz, Austria
    • Elisabethinen Hospital Linz
  • Salzburg, Austria
    • Salzburg Regional Hospital
  • Vienna, Austria
    • Medical University Vienna
  • Vienna, Austria
    • Hanusch Hospital
  • Wels, Austria
    • Hospital Wels-Grieskirchen
• Bulgaria
  • Sofia, Bulgaria
    • Specialized Hospital for Active Treatment of Hematological Diseases
  • Vratsa, Bulgaria
    • Multiprofile Hospital for Active Treatment - Hristo Botev, Vratsa, First Department of Internal Medicine
• Czech Republic
  • Brno, Czech Republic
    • University Hospital Brno
  • Hradec Kralove, Czech Republic
    • University Hospital Hradec Kralove
  • Prague, Czech Republic
    • Institute of Hematology and Blood Transfusion
  • Prague, Czech Republic
    • University Hospital Kralovske Vinohrady
  • Prague, Czech Republic
    • University Hospital Motol
• France
  • Marseilles, France
    • Institute Paoli-Calmettes
  • Paris, France
    • Hospital Saint-Louis
  • Poitiers, France
    • Clinical Research Center CIC
• Hungary
  • Budapest, Hungary
    • St Istvan and St Laszlo Hospital of Budapest
  • Debrecen, Hungary
    • University of Debrecen
  • Gyula, Hungary
    • Bekes County Pandy Kalman Hospital, 1st Department of Medicine, Hematology
  • Kaposvar, Hungary
    • Kaposi Mór County Teaching Hospital
  • Szeged, Hungary
    • University of Szeged, Albert Szent-Gyorgyi Clinical Center, Koranyi fasor 6
• Poland
  • Katowice, Poland
    • Andrzej Mielecki Independent Public Clinical Hospital of Medical University of Silesia in Katowice
  • Krakow, Poland
    • University Hospital in Cracow
  • Lublin, Poland
    • Independent Public Teaching Hospital No.1 in Lublin
  • Rzeszow, Poland
    • Fryderyk Chopin Provincial Specialized Hospital
  • Torun, Poland
    • Nicolaus Copernicus Municipal Specialist Hospital
  • Warsaw, Poland
    • Institute of Hematology and Transfusion Medicine
• Slovakia
  • Banska Bystrica, Slovakia
    • University Hospital with Outpatient Clinic F.D. Roosevelt
  • Bratislava, Slovakia
    • Saint Cyril and Metod University Hospital Bratislava
• Ukraine
  • Cherkasy, Ukraine
    • Cherkasy Regional Oncology Center, Regional Treatment and Diagnostics Hematology Center
  • Dnipropetrovsk, Ukraine
    • Dnipropetrovsk City Multispecialty Clinical Hospital #4
  • Kiev, Ukraine
    • National Research Center for Radiation Medicine, Institute of Clinical Radiology
  • Lviv, Ukraine
    • Institute of blood pathology and transfusion medicine
  • Zhytomyr, Ukraine
    • O.F. Herbachevskyi Regional Clinical Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Pegylated- Proline-Interferon alpha-2b; Pegylated-Proline-Interferon alpha-2b in a Pre-filled Pen single arm	Drug: Pegylated-Proline-Interferon alpha-2b in a Pre-filled Pen; 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.; Other Names: AOP2014

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate ease of self-administration of AOP2014	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).	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event	biweekly, using dedicated questionnaires	3 month
number of phlebotomies	biweekly	3 months
Disease response	The main efficacy evaluation criterion will be disease response defined as: • Hct (Hematocrit)< 45% without phlebotomy (at least 3 months since the last phlebotomy). The hematological parameters will be measured by the local laboratories at clinical sites.	3 months
Disease response	The main efficacy evaluation criterion will be disease response defined as: • PLTs (Platelets)< 400 x 109/L. The hematological parameters will be measured by the local laboratories at clinical sites.	3 months
Disease response	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.	3 months
blood parameters	first biweekly than monthly The main efficacy evaluation criterion will be disease response defined as: • Hct< 45% without phlebotomy (at least 3 months since the last phlebotomy). The hematological parameters will be measured by the local laboratories at clinical sites.	3 months
blood parameters	first biweekly than monthly The main efficacy evaluation criterion will be disease response defined as: • WBCs< 10 x 109/L. The hematological parameters will be measured by the local laboratories at clinical sites.	3 months
blood parameters	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.	3 months
spleen size	locally, Sonography will be used for measuring the spleen size (length). at Visit 1 and at the End of the study (week 12)	3 months
disease related symptoms	biweekly, using dedicated questionnaires	3 months
protocol-specific adverse events of special interest	biweekly, using dedicated questionnaires	3 months

Collaborators and Investigators

• Sponsor: AOP Orphan Pharmaceuticals AG
• Collaborators: PharmaEssentia Corporation (Co-Sponsor for USA)
• Investigators: Principal Investigator: Heinz Gisslinger, MD, Med Uni Wien

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: June 12, 2015
• First Submitted That Met QC Criteria: August 12, 2015
• First Posted (Estimate): August 14, 2015

Study Record Updates

• Last Update Posted (Estimate): February 17, 2016
• Last Update Submitted That Met QC Criteria: February 16, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Hematologic Diseases; Polycythemia; Bone Marrow Diseases; Interferon-alpha; Myeloproliferative Disorders; Polycythemia Vera; Peginterferon alfa-2b; Pegylated-Proline-interferon alpha-2b (AOP2014); PROUD-PV; CONTINUATION-PV; AOP Orphan; PEN-PV
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Polycythemia Vera; Polycythemia; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Interferon alpha-2
• Other Study ID Numbers: PEN-PV; 2014-001356-31 (EudraCT Number)