Clinical trial NCT02523638: Study to Assess the Self-administration of AOP2014 Using a Pen, Developed for the Treatment of Polycythemia Vera Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Polycythemia Vera
Keywords: Pegylated-Proline-interferon alpha-2b (AOP2014)
Polycythemia Vera
PEN-PV
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 (Co-Sponsor for USA)
First posted: 2015-08-14
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: To evaluate ease of self-administration of AOP2014
timeFrame: 3 months
Secondary outcomes:
measure: Adverse Event
timeFrame: 3 month
measure: number of phlebotomies
timeFrame: 3 months
measure: Disease response
timeFrame: 3 months
measure: Disease response
timeFrame: 3 months
measure: Disease response
timeFrame: 3 months
measure: blood parameters
timeFrame: 3 months
measure: blood parameters
timeFrame: 3 months
measure: blood parameters
timeFrame: 3 months
measure: spleen size
timeFrame: 3 months
measure: disease related symptoms
timeFrame: 3 months
measure: protocol-specific adverse events of special interest
timeFrame: 3 months
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: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Hematological Diseases
city: Vratsa
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Hristo Botev, Vratsa, First Department of Internal Medicine
city: Brno
country: Czech Republic
facility: University Hospital Brno
city: Hradec Kralove
country: Czech Republic
facility: University Hospital Hradec Kralove
city: Prague
country: Czech Republic
facility: Institute of Hematology and Blood Transfusion
city: Prague
country: Czech Republic
facility: University Hospital Kralovske Vinohrady
city: Prague
country: Czech Republic
facility: University Hospital Motol
city: Marseilles
country: France
facility: Institute Paoli-Calmettes
city: Paris
country: France
facility: Hospital Saint-Louis
city: Poitiers
country: France
facility: Clinical Research Center CIC
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: Katowice
country: Poland
facility: Andrzej Mielecki Independent Public Clinical Hospital of Medical University of Silesia in Katowice
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: 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: 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: