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THIS INFORMATION IS FOR NON-US HEALTHCARE PROVIDERS ONLY

The PROUD-PV Study

Ropeginterferon α-2b (AOP2014) versus Hydroxyurea in Polycythemia Vera

The PROUD-PV study is a phase III study to compare the efficacy and safety of the novel Ropeginterferon α-2b (AOP2014) versus Hydroxyurea (the current licensed therapy for this disease) in both HU naive and currently treated patients, diagnosed 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.

Study Outline

 

*) non-inferiority: Hematologic Response
**) benefit: durable Hematologic Response, PFS, PV symptom relief

 

Outcome Measures / Endpoints

Primary Outcome Measures / Primary Endpoints

  • Disease response rate* at 12 months 
    * 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

Secondary Outcome Measures / Secondary Endpoints

  • Disease response rate at 3, 6 and 9 months
  • JAK2 allelic burden changes
  • Time to response
  • Duration of response
  • Number of phlebotomies
  • Blood parameters
  • Spleen size
  • Disease related symptoms
  • Adverse events
  • Protocol-specific adverse events of special interest

Eligibility Criteria

Inclusion Criteria

  • 18 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

Exclusion Criteria

  • Any systematic cytoreduction for PV prior study entry with exception of HU for shorter than 3 years (see respective inclusion criterion)
  • 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
  • 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
  • Patients tested positively with TgAb and / or TPOAb at screening
  • History of major organ transplantation
  • History of uncontrolled severe seizure disorder
  • Leukocytopenia at the time of screening
  • Thrombocytopenia at the time of screening
  • History of malignant disease, including solid tumours and hematological malignancies (except basal cell and squamous cell carcinomas of the skin and carcinoma in situ of the cervix that have been completely excised and are considered cured) within the last 3 years

Contacts

Find more information about the PROUD-PV study on clinicaltrials.gov …