The Benefit/Risk Profile of AOP2014 in Low-risk Patients With PV

NCT03003325 | Completed Phase 2 DMC

• 1 other identifier: Low-PV
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 23

Brief Summary

The Low-PV study is a multicenter, phase II, randomized trial aimed to assess whether the addition of Pegylated Proline-interferon-alpha-2b to the best therapeutic current strategy available based on phlebotomies and low dose acetylsalicylic acid (ASA) could improve the efficacy of treatment of patients with PV at low risk of thrombosis (younger than 60 years and without prior vascular events), in term of control of recommended level of hematocrit \< 45%, over a period of 12 months.

Conditions

Polycythemia Vera

Keywords

low risk of thrombosis; Interferon

Outcome Measures

Primary Outcomes (1)

• Number of patients who maintains the median value of HCT< 45%, along 12 months, on number of patients randomized in each arm, per cent

  For each patient the median value of HCT percentage will be calculated from all measurements detected and reported every month (from baseline to 12-month visit or study end). A patient will be defined as responder (achieving PEp) when he maintains the median value of HCT \< 45%, after undergoing treatments according to this protocol, for up 12 months. A patient will be defined as non-responder (not achieving PEp) when 1. Does not maintain the median value of HCT \< 45%, after undergoing treatments according to this protocol, for up 12 months, or 2. Is in need of any additional chemotherapeutic and/or cytoreductive treatment aimed to manage disease due to disease progression.

  12 months

Secondary Outcomes (7)

• Median number of phlebotomies performed

  12 months, 24 months

• Number of patients achieving hematological response (as defined below in 'Description') on number of patients randomized in each arm, per cent,

  12 months, 24 months

• Proportion (rate per cent) of patients with not palpable spleen

  12 months, 24 months

• Janus kinase-2 allele burden reduction or complete molecular remission

  12 months, 24 months

• Bone marrow histological remission

  24 months

Other Outcomes (1)

• Quality of Life (QoL)

  12 months, 24 months

Study Arms (2)

Phlebotomies + ASA

ACTIVE COMPARATOR

Conventional treatment based on phlebotomies and low dose (100 mg) of acetylsalicylic acid (ASA)

Procedure: Phlebotomies; Drug: ASA

Phlebotomies + ASA + AOP2014

EXPERIMENTAL

Conventional treatment based on phlebotomies, low dose (100 mg) of acetylsalicylic acid (ASA) plus the addition of 100 µg of Pegylated Proline-Interferon alpha-2b (AOP2014) once every 14 days (subcutaneously).

Drug: AOP2014; Procedure: Phlebotomies; Drug: ASA

Interventions

AOP2014 DRUG

AOP2014 will be supplied to the patients as pre-filled auto-injection pens, containing 250 µg of active drug (0.5 ml solution for injection). One pen may be used twice within a time period of 4 weeks. Hence investigators will provide one prefilled pen at every monthly visit. AOP2014 will be self-injected subcutaneously by patients once every 14 days at the single doses of 100 µg (0.2 ml).

Also known as: Pegylated-Proline-Interferon α-2b, P1101

Phlebotomies + ASA + AOP2014

Phlebotomies PROCEDURE

According to current common clinical practice the regimen must be selected accordingly to maintain the recommended level of HCT\< 45%. Once normalization of the hematocrit has been achieved, blood counts at regular intervals (every 4 weeks) will establish the frequency of future phlebotomies. Sufficient blood should be removed to maintain the hematocrit below 45%.

Also known as: blood removing

Phlebotomies + ASA; Phlebotomies + ASA + AOP2014

ASA DRUG

100 mg/daily of ASA is recommended (when there are not contraindications) according with current guidelines for this risk class of patients

Also known as: Acetylsalicylic Acid

Phlebotomies + ASA; Phlebotomies + ASA + AOP2014

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-60 years
• Diagnosis of Polycythemia Vera according to World Health Organization 2016 criteria
• Diagnosis of Polycythemia Vera including a recent bone marrow (BM) biopsy (performed within 3 years prior randomization in the study) and never treated with cytoreductive drugs
• HCT\<45%
• Ability and willingness to comply with all study requirements
• Signed written informed consent.

You may not qualify if:

• Any previous well documented cardiovascular PV-related events (see Appendix 1 for description)
• Previous cytoreductive drugs
• Known hypersensitivity or contraindications to the Investigational Medicinal Product (Pegylated Proline-Interferon alpha-2b) including:
• 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; patients tested positively with Thyroglobulin antibody and / or TPOAb at screening; documented autoimmune disease at screening or in the medical history; history or presence of depression requiring treatment with antidepressant; any risk of suicide at screening or previous suicide attempts;
• Previous exposure to a non-pegylated or pegylated interferon α
• Clinically relevant pulmonary infiltrates, pneumonia, and pneumonitis
• Systemic infections, e.g. hepatitis B, hepatitis C, or HIV at screening
• Significant liver (AST or alanine aminotransferase \> 2.5 times ULN) or renal disease (creatinine \> 2 mg/ml)
• Presence of any life-threatening condition or of any disease (e.g. cancer) that is likely to significantly shorten life expectancy
• History of active substance or alcohol abuse within the last year
• Any condition that in the opinion of the investigator would jeopardize the evaluation of efficacy or safety or be associated with poor adherence to the protocol
• Pregnant or lactating women and women\*/men of childbearing potential who are not using or are not willing to use any effective means of contraception (i.e. sexual abstinence, hormonal contraceptive, intra-uterine device, barrier method such as diaphragms or condoms, surgical methods).
• Pregnancy test will be performed in order to ascertain negativity of human chorionic gonadotropin (β-hCG) test and confirm that childbearing women are not pregnant.

Sponsors & Collaborators

• FROM- Fondazione per la Ricerca Ospedale di Bergamo- ETS: lead
• AOP Orphan Pharmaceuticals AG: collaborator

Study Sites (23)

U.O. Ematologia, Ospedale Casa Sollievo della Sofferenza Istituto di Ricovero e Cura a Carattere Scientifico

San Giovanni Rotondo, (FG) Puglia, 71013, Italy

Location

U.O. Ematologia con Trapianto, Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari

Bari, Apulia, 70120, Italy

Location

Azienda Ospedaliera Universitaria Federico II di Napoli

Napoli, Campania, 80131, Italy

Location

Divisione Ematologia Policlinico S. Orsola - Malpighi

Bologna, Emilia-Romagna, 40138, Italy

Location

Clinica Ematologica, Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia"

Udine, Friuli Venezia Giulia, 33100, Italy

Location

UCSC Ematologia, Fondazione Policlinico Universitario "Agostino Gemelli"Università Cattolica del Sacro Cuore

Rome, Lazio, 00168, Italy

Location

UOC Ematologia, ASST Papa Giovanni XXIII

Bergamo, Lombardy, 24127, Italy

Location

Divisione Oncoematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Lombardy, 20122, Italy

Location

Divisione Ematologia ASST, Grande Ospedale Metropolitano Niguarda

Milan, Lombardy, 20162, Italy

Location

Divisione Ematologia, ASST di MONZA - Ospedale San Gerardo di Monza

Monza, Lombardy, 20900, Italy

Location

Divisione Ematologia, Fondazione IRCCS Policlinico San Matteo

Pavia, Lombardy, 27100, Italy

Location

U.O. Ematologia, Ospedale di Circolo e Fondazione Macchi Varese

Varese, Lombardy, 21100, Italy

Location

S.C. Ematologia Azienda Ospedaliera S. Croce e Carle Cuneo

Cuneo, Piedmont, 12100, Italy

Location

SCDU Ematologia, A.O.U. Maggiore della Carità

Novara, Piedmont, 28100, Italy

Location

S.C. Ematologia, AOU- Presidio Ospedaliero Molinette

Turin, Piedmont, 10126, Italy

Location

Unità Operativa Complessa di Emostasi Azienda Ospedaliero-Universitario "Policlinico Vittorio-Emanuele - Presidio Ospedaliero Ferrarotto

Catania, Sicily, 95124, Italy

Location

UOC Ematologia, Azienda Ospedaliera Universitaria Policlinico "G. Martino"

Messina, Sicily, 98100, Italy

Location

Divisione Ematologia Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone" Palermo

Palermo, Sicily, 90127, Italy

Location

SOD Ematologia AUOC Azienda Ospedaliero-Universitaria "Careggi"

Florence, Tuscany, 50134, Italy

Location

Clinica Medica I Azienda Ospedaliera di Padova

Padua, Veneto, 35128, Italy

Location

Divisione Ematologia, Ospedale Borgo Roma

Verona, Veneto, 37134, Italy

Location

Divisione Ematologia, Ospedale San Bortolo

Vicenza, Veneto, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

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MeSH Terms

Conditions

Polycythemia Vera

Interventions

Blood Specimen Collection; Aspirin

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)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Tiziano Barbui, Professor

  Fondazione per la Ricerca Ospedale Maggiore di Bergamo (FROM)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2016
• First Posted: December 28, 2016
• Study Start: February 2, 2017
• Primary Completion: March 31, 2022
• Study Completion: March 31, 2023
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (23)