Best available therapy, as chosen by the investigator for patients who had been on HU in the 1 Year PROUD-PV study

AOP2014 for those patients who had been on AOP2014 in the PROUD-PV study

Polycythemia Vera

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.

Pegylated-Proline-interferon alpha-2b

Best available therapy as selected by the investigator

Best available therapy (BAT)

LKH Graz

University Hospital Innsbruck

Elisabethinen Hospital Linz

Salzburg Regional Hospital

Hanusch Hospital

Medical University Vienna

Hospital Wels-Grieskirchen

University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv

Specialized Hospital for Active Treatment of Hematological Diseases

Multiprofile Hospital for Active Treatment "Sveta Marina", Varna

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

University Hospital Brno

University Hospital Hradec Kralove

University Hospital Kralovske Vinohrady

University Hospital Motol

Institute Paoli-Calmettes

Hospital Saint-Louis

Clinical Research Center CIC

Aachen University Hospital, Medical Clinic IV

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

University Hospital Carl Gustav Carus, Medical Clinic and Polyclinic I

St Istvan and St Laszlo Hospital of Budapest

University of Debrecen

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

Kaposi Mor County Teaching Hospital

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

University Hospital in Cracow

Independent Public Teaching Hospital No.1 in Lublin

Fryderyk Chopin Provincial Specialized Hospital

Nicolaus Copernicus Municipal Specialist Hospital

Institute of Hematology and Transfusion Medicine

Emergency Clinical County Hospital Brasov

Bucharest University Emergency Hospital

Coltea Clinical Hospital

Baranov Republican Hospital

Samara Kalinin Regional Clinical Hospital

Komi Republican Oncology Center

Tula Regional Clinical Hospital

Yaroslavl Regional Clinical Hospital

University Hospital with Outpatient Clinic F.D. Roosevelt

Saint Cyril and Metod University Hospital Bratislava

Hospital del Mar

Cherkasy Regional Oncology Center, Regional Treatment and Diagnostics Hematology Center

Dnipropetrovsk City Multispecialty Clinical Hospital #4

National Research Center for Radiation Medicine, Institute of Clinical Radiology

Institute of Blood Pathology and Transfusion Medicine

O.F. Herbachevskyi Regional Clinical Hospital

AOP2014 vs. BAT in Patients With Polycythemia Vera Who Previously Participated in the PROUD-PV Study.

An Open-label, Multicenter, Phase IIIb Study Assessing the Long-term Efficacy and Safety of AOP2014 and Standard First Line Treatment (BAT) in Patients With Polycythemia Vera Who Previously Participated in the PROUD-PV Study

The primary efficacy endpoint will be the rate of disease response at assessment visits (every 3 months).
The co-primary efficacy evaluation criterion will be (1) disease response defined as hematologic response: Hct<45% without phlebotomy (at least 3 months since the last phlebotomy), PLTs<400 x 109/L, WBCs<10 x 109/L, and normal spleen size, and (2) disease response defined as hematologic response (Hct<45% without phlebotomy (at least 3 months since the last phlebotomy), PLTs<400 x 109/L, WBCs<10 x 109/L), resolution and/or clinically improvement of disease-related signs (clinical significant splenomegaly) and disease-related symptoms (microvascular disturbances, pruritus, headache).

AOP Orphan Pharmaceuticals AG

PharmaEssentia (Co-Sponsor for USA)

Participants will be given written educational material to encourage dietary change towards a better quality diet. Educational material will be adapted from resources used in previous dietary intervention studies.

Participants will also be given the educational material, but will be encouraged to make dietary change using individualized recommendations incorporating food markers of specific components of a high quality diet. Food markers of diet quality will be used to develop an algorithm to deliver personalized dietary advice. Based on biomarker data, a system of categorization of biomarker status will be developed, alongside dietary advice related to this biomarker categorization, and decision trees created, as previously described in the Food4Me study, to ensure standardized delivery of advice within this intervention arm.

Cardiovascular Diseases

Personalised dietary advice and educational material

Educational material

The Efficacy of Individualized Dietary Advice in Improving Diet Quality and Cardiovascular Health

Dietary intake will be assessed using an online version of the Prime Diet Quality Score (PDQS). Foods are classified as healthy and unhealthy. Points will be assigned according to the following criteria: 0-1 serving/wk (0 point) compared with 2-3 servings/wk (1 point) compared with ≥4 servings/wk (2 points) for the healthy food groups. Scoring will be reversed and points deducted for the unhealthy food groups. Points for each food group will be then summed to give an overall score. The PDQS has 21 food groups and ranges from 0 to 42 total points.

Questionnaire to assess number of units consumed weekly

Questionnaire to assess usual medication use (drug name, dose and frequency of use)

Physical activity using an accelerometer; data to be used will be total step count

Weight will be measured in kg using calibrated scales.

Waist and hip circumference will be measured in cm according to standardised operating procedures using a tape measure.

Height will be measured in metres using a stadiometer.

Body composition (% body fat) will be measured using bioelectrical impedence (Bodystat 1500).

Blood pressure will be measured twice from the right arm, using an automated Omron sphygmomanometer, with the participant sitting quietly for at least five minutes.

Serum lipids (total cholesterol, HDL-C, and TG) and whole blood HbA1c will be assessed by enzymatic assays (Randox Ltd, Crumlin, NI and Glen Bio, Antrim, NI) on an I-Lab 600 auto-analyzer. LDL-C will be calculated.

The following biomarkers will be used to assess nutritional status response to the dietary intervention: red meat - methylhistidines and carnosine; white meat - TMAO, guanidoacetate, anserine; fruit and vegetables -- proline betaine, isothiocyanates, S-methyl-L-cysteine sulfoxide, and tartaric acid; wholegrains - alkylresorcinols; coffee - phenolic acids, N-methylpyridinium, trigonelline, 2-furoylglycine; SSBs -- formate, citrulline, taurine, and isocitrate) red meat- methylhistidines; oily fish- omega-3 index; fruit and vegetables- total carotenoids and proline betaine; wholegrain- alkylresorcinols.

Sample handling and nucleic acid purifications will be performed following an established protocol. Illumina DNA-seq libraries with fragment length of ~300 bp will be generated as previously described, with Pippen prep size selection. For RNA-seq, 5ug of RNA will be enriched for mRNA and subjected to strand-specific cDNA synthesis using established protocols. Paired-end sequencing (e.g. 150x150 nt) will be performed on the Illumina HiSeq platform.

At early planning stage of study - undecided.

Jayne Woodside, PhD

Professoe

Queen's University, Belfast

University College Dublin

Harvard School of Public Health

Randomised parallel group dietary intervention: two group.

All outcomes will be conducted blind, including the primary outcome (diet quality score), laboratory analysis and cardiometabolic health marker assessment.

white/proline

AOP2014 vs. BAT in Patients With Polycythemia Vera Who Previously Participated in the PROUD-PV Study.

The Efficacy of Individualized Dietary Advice in Improving Diet Quality and Cardiovascular Health

Baza e të dhënave më e plotë e bimëve medicinale e mbështetur nga shkenca