Pegylated Interferon Alpha-2b Versus Hydroxyurea in Polycythemia Vera

NCT01949805 | Completed Phase 3 DMC

• 2 other identifiers: PROUD-PV2012-005259-18
• Study Type: interventional
• Target: 257
• Locations: 14 countries
• Sites: 58

Brief Summary

Phase III study to compare the efficacy and safety of the novel monopegylated interferon alpha 2b AOP2014 versus Hydroxyurea (the current licensed therapy for this disease). One year treatment of patients with polycythemia vera. Objective is to demonstrate non-inferiority of AOP2014 vs. HU in terms of disease response rate in both HU naïve and currently treated patients, diagnosed with Polycythemia Vera. Response is measured as normalisation of key lab parameters as well as normalized spleen size.

Conditions

Polycythemia Vera

Outcome Measures

Primary Outcomes (1)

• Disease response rate

  Disease response rate is defined as hematocrit \<45% without phlebotomy (at least 3 months since last phlebotomy), platelets \<400 G/L, leukocytes \<10 G/L , and normal spleen size

  Month 12

Secondary Outcomes (10)

• Disease response

  at month 3, 6 and 9

• JAK2 allelic burden changes

  at month 6 and 12

• time to response

  from inclusion until first response confirmation

• duration of response

  during the 12 months of study duration

• number of phlebotomies

  from inclusion until month 12

Study Arms (2)

Hydroxyurea

ACTIVE COMPARATOR

Hydroxyurea capsules (500 mg each). Daily intake of doses from 500 mg Q2D to 3000 mg QD

Drug: Hydroxyurea

Peg-P-IFN-alpha-2b (AOP2014)

EXPERIMENTAL

Peg-P-IFN-alpha-2b at 50mcg to max 500 mcg, given every other week as one subcutanous injection

Drug: Peg-P-IFN-alpha-2b (AOP2014)

Interventions

Peg-P-IFN-alpha-2b (AOP2014) DRUG

Pegylated interferon alpha 2b given Q2W as SC injection

Also known as: AOP2014, P1101

Peg-P-IFN-alpha-2b (AOP2014)

Hydroxyurea DRUG

Hydroyurea capsules taken daily po

Also known as: HU, Hydroxycarbamide, brand name Litalir (or other)

Hydroxyurea

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• Diagnosis of Polycythemia Vera according to the WHO 2008 criteria (Barbui et al, 2011) with the mandatory presence of JAK2V617F mutation as the major disease criterion.
• For previously cytoreduction untreated patients - documented need of cytoreductive treatment
• \- leukocytosis (WBC\>10G/L for two measurements within one week)
• For patients currently treated or pre-treated with HU, all of the following criteria:
• being non responders (as defined by the response criteria for primary endpoint)
• total HU treatment duration shorter than three years
• no documented resistance or intolerance as defined by modified Barosi et al, 2009 criteria
• Hospital Anxiety and Depression Scale (HADS) score 0-7 on both subscales
• Patients with HADS score of 8-10 inclusive on either or both of the subscales may be eligible following psychiatric assessment that excludes clinical significance of the observed symptoms in the context of potential treatment with an interferon alpha
• Signed written informed consent

You may not qualify if:

• Any contraindication to any of the IMPs (pegylated interferon or hydroxyurea) or their excipients
• Any systemic exposure to a non-pegylated or pegylated interferon alpha
• Documented autoimmune disease at screening or in the medical history
• Clinically relevant pulmonary infiltrates, pneumonia, and pneumonitis at screening
• Systemic infections, e.g. hepatitis B, hepatitis C, or HIV at screening
• Known PV-related thromboembolic complications in the abdominal area (e.g. portal vein thrombosis, Budd-chiari syndrome) and/or splenectomy in the medical history
• Any investigational drug less than 6 weeks prior to the first dose of study drug or not recovered from effects of prior administration of any investigational agent
• History or presence of depression requiring treatment with antidepressant
• HADS score equal to or above 11 on either or both of the subscales
• Any risk of suicide at screening or previous suicide attempts
• Any significant morbidity or abnormality which may interfere with the study participation
• Pregnancy and breast-feeding females of reproductive potential and males not using effective means of contraception
• History of active substance or alcohol abuse within the last year
• Evidence of severe retinopathy (e.g. cytomegalovirus retinitis, macular degeneration) or clinically relevant ophthalmological disorder (due to diabetes mellitus or hypertension)
• Thyroid dysfunction not adequately controlled

Sponsors & Collaborators

• AOP Orphan Pharmaceuticals AG: lead
• PharmaEssentia (Co-Sponsor for USA): collaborator

Study Sites (58)

LKH Graz

Graz, Austria

Location

University Hospital Innsbruck

Innsbruck, Austria

Location

Elisabethinen Hospital Linz

Linz, Austria

Location

Salzburg Regional Hospital

Salzburg, Austria

Location

Hanusch Hospital

Vienna, Austria

Location

Medical University Vienna

Vienna, Austria

Location

Hospital Wels-Grieskirchen

Wels, Austria

Location

Centre du Cancer et D'hematologie

Brussels, Belgium

Location

UZA, Antwerp University Hospital

Edegem, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

Haematolgy, University of Liège

Liège, Belgium

Location

University Multiprofile Hospital for Active Treatment "Sveti Georgi"

Plovdiv, Bulgaria

Location

Specialized Hospital for Active Treatment of Hematological Diseases

Sofia, Bulgaria

Location

Multiprofile Hospital for Active Treatment "Sveta Marina"

Varna, Bulgaria

Location

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

Vratsa, Bulgaria

Location

University Hospital Brno

Brno, Czechia

Location

University Hospital Hradec Kralove

Hradec Králové, Czechia

Location

Institute of Hematology and Blood Transfusion

Prague, Czechia

Location

University Hospital Kralovske Vinohrady

Prague, Czechia

Location

University Hospital Motol

Prague, Czechia

Location

Institute Paoli-Calmettes

Marseille, France

Location

Hospital Saint-Louis

Paris, France

Location

Clinical Research Center CIC

Poitiers, France

Location

Aachen University Hospital, Medical Clinic IV

Aachen, Germany

Location

University Hospital Bonn, Center for Internal Medicine, Medical Clinic and Outpatient Clinic III

Bonn, Germany

Location

University Hospital Carl Gustav Carus, Medical Clinic and Polyclinic I

Dresden, Germany

Location

St Istvan and St Laszlo Hospital of Budapest

Budapest, Hungary

Location

University of Debrecen

Debrecen, Hungary

Location

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

Gyula, Hungary

Location

Kaposi Mor County Teaching Hospital

Kaposvár, Hungary

Location

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

Szeged, Hungary

Location

Careggi University Hospital

Florence, Italy

Location

Foundation IRCCS Policlinico San Matteo

Pavia, Italy

Location

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

Katowice, Poland

Location

University Hospital in Cracow

Krakow, Poland

Location

Independent Public Teaching Hospital No.1 in Lublin

Lublin, Poland

Location

Fryderyk Chopin Provincial Specialized Hospital

Rzeszów, Poland

Location

Nicolaus Copernicus Municipal Specialist Hospital

Torun, Poland

Location

Institute of Hematology and Transfusion Medicine

Warsaw, Poland

Location

Emergency Clinical County Hospital Brasov

Brasov, Romania

Location

Bucharest University Emergency Hospital

Bucharest, Romania

Location

Coltea Clinical Hospital

Bucharest, Romania

Location

"Prof. Dr. Ion Chiricuta" Institute of Oncology

Cluj-Napoca, Romania

Location

Baranov Republican Hospital

Petrozavodsk, Russia

Location

First Pavlov State Medical University of St. Petersburg

Saint Petersburg, Russia

Location

Samara Kalinin Regional Clinical Hospital

Samara, Russia

Location

Komi Republican Oncology Center

Syktyvkar, Russia

Location

Tula Regional Clinical Hospital

Tula, Russia

Location

Yaroslavl Regional Clinical Hospital

Yaroslavl, Russia

Location

University Hospital with Outpatient Clinic F.D. Roosevelt

Banská Bystrica, Slovakia

Location

Saint Cyril and Metod University Hospital Bratislava

Bratislava, Slovakia

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Cherkasy Regional Oncology Center, Regional Treatment and Diagnostics Hematology Center

Cherkasy, Ukraine

Location

Dnipropetrovsk City Multispecialty Clinical Hospital #4

Dnipropetrovsk, Ukraine

Location

National Research Center for Radiation Medicine, Institute of Clinical Radiology

Kiev, Ukraine

Location

Institute of Blood Pathology and Transfusion Medicine

Lviv, Ukraine

Location

O.F. Herbachevskyi Regional Clinical Hospital

Zhytomyr, Ukraine

Location

Related Publications (1)

• Verger E, Soret-Dulphy J, Maslah N, Roy L, Rey J, Ghrieb Z, Kralovics R, Gisslinger H, Grohmann-Izay B, Klade C, Chomienne C, Giraudier S, Cassinat B, Kiladjian JJ. Ropeginterferon alpha-2b targets JAK2V617F-positive polycythemia vera cells in vitro and in vivo. Blood Cancer J. 2018 Oct 4;8(10):94. doi: 10.1038/s41408-018-0133-0.

  PMID: 30287855 DERIVED

MeSH Terms

Conditions

Polycythemia Vera

Interventions

peginterferon alfa-2b; Hydroxyurea

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Study Officials

• Heinz Gisslinger, MD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2013
• First Posted: September 25, 2013
• Study Start: September 1, 2013
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: November 28, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (5); RU (6); SL (2); ES (2); PL (6); HU (5); IT (2); RO (4); DE (3); BU (4); UA (5); FR (3); BE (4); AU (7)