Clinical Trial: Pegylated Interferon Alpha-2b Versus Hydroxyurea in Polycythemia Vera

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized, Open-label, Multicenter, Controlled, Parallel Arm, Phase III Study Assessing the Efficacy and Safety of AOP2014 vs. Hydroxyurea in Patients With Polycythemia Vera

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.

Detailed Summary:

Hydroxyurea is an established first-line treatment option currently approved in several European countries for Polycythemia Vera (PV) patients requiring a cytoreductive therapy (Barbui et al, 2011). Clinical trials have shown that HU is an effective drug for preventing thrombosis in PV compared to phlebotomy (Michiels et al, 1999).

The main concern of a long term treatment with HU is its potential leukaemogenicity: based on the mechanism of action, HU can potentially accelerate the accumulation of mutations in DNA and increase the risk of leukaemic transformation (Dingli et Tefferi, 2006). However, there is currently no clear clinical data to confirm leukaemogenicity of HU in patients with PV (Tefferi, 2012).

Even though IFN-alpha has shown its activity in PV in the 1980s, it is still considered as an experimental treatment in Europe due to pending approval in this indication (Barbui et al, 2011). It induces major or complete molecular remissions in patients with PV accompanied by a reduction in the risk of thrombosis and bleeding - the major determinants of morbidity in this indication (Hasselbalch, 2011). However, only low doses are tolerated and significant adverse effects from long-term use may limit its usefulness.

Pegylated interferons are better tolerated and are the preferred options of treatment in PV patients (Kiladjian et al, 2008) despite the lack of evidences based on well-designed randomized controlled clinical studies.

AOP2014 is a next generation pegylated interferon (Peg-P-IFN-alpha-2b), with the addition of proline in the N-terminal end.

AOP2014 like all interferon suppresses the malignant clone causing PV and subsequently is expected to possibly defer the o
Sponsor: AOP Orphan Pharmaceuticals AG

Current Primary Outcome: Disease response rate [ Time Frame: Month 12 ]

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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Disease response [ Time Frame: at month 3, 6 and 9 ]
  • JAK2 allelic burden changes [ Time Frame: at month 6 and 12 ]
  • time to response [ Time Frame: from inclusion until first response confirmation ]
    will be measured during the study period of 12 months
  • duration of response [ Time Frame: during the 12 months of study duration ]
    from the first documented response on study
  • number of phlebotomies [ Time Frame: from inclusion until month 12 ]
  • blood parameters [ Time Frame: from inclusion until month 12 ]
    biweekly
  • spleen size [ Time Frame: at month 3, 6, 9 and 12 ]
    both centrally (blinded assessment) and locally
  • disease related symptoms [ Time Frame: from inclusion until month 12 ]
    biweekly
  • adverse events [ Time Frame: from inclusion until month 12 ]
    biweekly
  • protocol-specific adverse events of special interest [ Time Frame: from inclusion until month 12 ]
    biweekly


Original Secondary Outcome:

  • Disaese response [ Time Frame: at month 3, 6 and 9 ]
  • JAK2 allelic burden changes [ Time Frame: at month 6 and 12 ]
  • time to response [ Time Frame: from inclusion until first response confirmation ]
    will be measured during the study period of 12 months
  • duration of response [ Time Frame: during the 12 months of study duration ]
    from the first documented response on study
  • number of phlebotomies [ Time Frame: from inclusion until month 12 ]
  • blood parameters [ Time Frame: from inclusion until month 12 ]
    biweekly
  • spleen size [ Time Frame: at month 3, 6, 9 and 12 ]
    both centrally (blinded assessment) and locally
  • disease related symptoms [ Time Frame: from inclusion until month 12 ]
    biweekly
  • adverse events [ Time Frame: from inclusion until month 12 ]
    biweekly
  • protocol-specific adverse events of special interest [ Time Frame: from inclusion until month 12 ]
    biweekly


Information By: AOP Orphan Pharmaceuticals AG

Dates:
Date Received: September 6, 2013
Date Started: September 2013
Date Completion:
Last Updated: November 24, 2016
Last Verified: November 2016