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

Polycythemia Vera Clinical Trial

— PEN-PV  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02523638
• Other study ID #: PEN-PV
• Secondary ID: 2014-001356-31
• Status: Completed
• Phase: Phase 3
• First received: June 12, 2015
• Last updated: February 16, 2016
• Start date: July 2015
• Est. completion date: December 2015

Study information

• Verified date: February 2016
• Source: AOP Orphan Pharmaceuticals AG
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Austrian Medicines and Medical Devices AgencyBulgaria: Ministry of HealthCzech Republic: State Institute for Drug ControlFrance: Agence Nationale de Sécurité du Médicament et des produits de santéHungary: National Institute of PharmacyPoland: Ministry of HealthRussia: Ministry of Health of the Russian FederationSlovakia: State Institute for Drug ControlUkraine: Ministry of Health
• 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 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).

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 information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 99 Years

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Polycythemia
• Polycythemia Vera

Intervention

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.

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	Specialized Hospital for Active Treatment of Hematological Diseases	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment - Hristo Botev, Vratsa, First Department of Internal Medicine	Vratsa
Czech Republic	University Hospital Brno	Brno
Czech Republic	University Hospital Hradec Kralove	Hradec Kralove
Czech Republic	Institute of Hematology and Blood Transfusion	Prague
Czech Republic	University Hospital Kralovske Vinohrady	Prague
Czech Republic	University Hospital Motol	Prague
France	Institute Paoli-Calmettes	Marseilles
France	Hospital Saint-Louis	Paris
France	Clinical Research Center CIC	Poitiers
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	Andrzej Mielecki Independent Public Clinical Hospital of Medical University of Silesia in Katowice	Katowice
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
Slovakia	University Hospital with Outpatient Clinic F.D. Roosevelt	Banska Bystrica
Slovakia	Saint Cyril and Metod University Hospital Bratislava	Bratislava
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 (Co-Sponsor for USA)

Countries where clinical trial is conducted

Austria,  Bulgaria,  Czech Republic,  France,  Hungary,  Poland,  Slovakia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Adverse Event	biweekly, using dedicated questionnaires	3 month	Yes
Secondary	number of phlebotomies	biweekly	3 months	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	disease related symptoms	biweekly, using dedicated questionnaires	3 months	No
Secondary	protocol-specific adverse events of special interest	biweekly, using dedicated questionnaires	3 months	Yes