Study to Assess the Self-administration of AOP2014 Using a Pen, Developed for the Treatment of Polycythemia Vera Patients

An Open-label, Single Arm, Phase III Study to Assess the Self-administration of AOP2014 Using a Pre-filled Pen, Developed for the Treatment of Polycythemia Vera Patients

Polycythemia Vera (PV) is a disease of bone marrow stem cells that manifests in a drastic increase of red blood cells and frequently also of white blood cells. The "thickening" of the blood in relation with a modified function of the cells has several consequences like increased blood pressure, pruritus of the skin, fatigue, disturbed blood circulation in the brain as well as fingers and toes and an increased risk of arterial and venous thrombosis (thrombosis is the formation of a blood clot in a vessel); like stroke, cardiac infarction, deep vein thrombosis in the legs. In case of a strong increase of platelets there is an additional risk of bleedings. As the disease progresses the size of spleen and liver increased in most cases and the bone marrow shows signs of fibrosis. In some cases of PV a progression at a later time point to a leukemia (increased formation of white blood cells) can occur.

The aim of this study is to assess the ease of AOP2014 self-administration using dedicated questionnaires.

• To assess safety and tolerability: adverse events (AEs), laboratory parameters, electrocardiogram (ECG) throughout study.
• To assess maintenance of the blood efficacy parameters Hct (Hematocrit), WBC (white blood cells) and PLTs (platelets) and spleen size (comparing values at Visit P7 vs. values at Visit P1).
• To assess the feasibility of AOP2014 self-administration: defined as the ability of the patients to use the pen as a self-administration tool (ease of handling, safety, tolerability and efficacy).

This is a Phase III, single-arm study performed in patients who completed the AOP2014 arm of the PROUD-PV study or are currently participating in the CONTINUATION-PV study. After signing the informed consent form (ICF), approximately 30 patients will be enrolled consecutively into the study at participating sites according to the inclusion and exclusion criteria.

Inclusion Criteria:

1. Patients who either completed the 12 months AOP2014 treatment arm of the PROUD-PV study, or are currently participating in the CONTINUATION-PV, and at the "EoT visit" (End of treatment visit) of the PROUD-PV study or two weeks after the last assessment visit of the CONTINUATION-PV study, fulfill at least one of the following criteria:

   • Normalization of at least two out of three main blood parameters (Hct (Hematocrit), PLTs (Platelets) and WBCs (white blood cells) if these parameters were moderately increased (Hct<50%, WBCs<20 x 109/L, PLTs<600 x 109/L) at baseline visit of the PROUD-PV study, OR
   • >35% decrease of at least two out of three main blood parameters (Hct, PLTs and WBCs) if these parameters were massively increased (Hct>50%, WBCs>20 x 109/L, PLTs >600 x 109/L), at baseline visit of the PROUD-PV study, OR
   • Normalization of spleen size, if spleen was enlarged at baseline visit of the PROUD-PV study, OR
   • Otherwise a clear, medically verified benefit from treatment with AOP2014 (e.g. normalization of disease-related micro-vasculatory symptoms, substantial decrease of JAK2 (Januskinase 2) allelic burden).

2. Signed written ICF.

Exclusion Criteria:

Withdrawal criteria, as specified in the PROUD-PV and CONTINUATION-PV studies, which mandate treatment discontinuation.

1. Non-recovery from the AOP2014 related toxicities to the grade (usually, Grade I) which allows continuation of the treatment.
2. HADS (Hospital Anxiety and Depression Scale) score of 11 or higher on either or both of the subscales, and /or development or worsening of clinically significant depression or suicidal thoughts.
3. Progressive and clinically significant increase of liver enzyme levels despite dose reduction, or if such increase is accompanied by increased bilirubin level, any signs or symptoms of a clinically significant autoimmune disease.
4. Clinically significant development of a new ophthalmologic disorder, or worsening of a pre-existing one, during the study.
5. Loss of efficacy of AOP2014 or any comparable situation where no further benefits of treatment continuation are expected by the investigator.