Polycythemia Vera MedDRA version: 17.0 Level: LLT Classification code 10036061 Term: Polycythemia vera System Organ Class: 100000004864
Conditions
Interventions
Product Name: Pegylated proline-interferon alpha-2b
Product Code: AOP2014
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PEGylated Proline-interferone alpha-2b recombinant
CAS Number
P1101
Other descriptive name: PEGINTERFERON ALFA-2B
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.5-
Trade Name: Hydrea
Pharmaceutical Form: Caps
Sponsors
AOP Orphan Pharmaceuticals AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 18 years or older 2. Diagnosis of Polycythemia Vera according to the WHO 2008 criteria with the mandatory presence of JAK2V617F mutation as the major disease criterion. 3. For previously cytoreduction untreated patients – documented need of cytoreductive treatment (any of the following criteria): -age >60 years at the planned day of the first drug administration -at least one previous well documented major cardiovascular PV-related event (see appendix 6 for definitions), except bleeding and PV-related thromboembolic complications in the abdominal area, see excl. criterion 7) in the medical history -poor tolerance (defined as a phlebotomy/ procedure-related adverse event causing significant adverse impact on the patient and limiting ability to apply phlebotomy with the intention to keep Hct 45%, or if one phlebotomy was not able to reduce Hct level to 10 x 109/L for two measurements within one week) 4. 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 in this protocol) -total HU treatment duration shorter than three years -no documented resistance or intolerance as defined by modified Barosi et al, 2009 criteria 5. Hospital Anxiety and Depression Scale (HADS) score 0-7 on both subscales 6. Patients with a HADS score of 8-10 inclusive on either or both of the subscales may be eligible following psychiatric assessment 7. Signed written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1.Any systemic cytoreduction for PVin the medical history prior to study entry with the exception of HU for shorter than 3 years (see respective inclusion criterion) 2.Any contraindication to any of the IMPs (pegylated interferon or hydroxyurea) or their excipients 3.Any systemic exposure to a non-pegylated or pegylated interferon alpha in the medical history 4.Documented autoimmune disease at screening or in the medical history 5.Clinically relevant pulmonary infiltrates, pneumonia, and pneumonitis at screening 6. Infections with systemic manifistation, e.g. hepatitis B, hepatitis C, or HIV at screening 7.Known, PV-related thromboembolic complications in the abdominal area (e.g. portal vein thrombosis, Budd-chiari syndrome) 8.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 9.History or presence of depression requiring treatment with antidepressant 10.HADS score equal to or above 11 on either or both of the subscales 11.Any risk of suicide at screening or previous suicide attempts 12.Any significant morbidity or abnormality which may interfere with the study participation 13.Pregnancy and breast-feeding females of reproductive potential and males not using effective means of contraceptionNote: women of childbearing potential not using effective contraceptive methods are not eligible for the study. A woman of childbearing potential is defined as any female who has experienced menarche and who is not postmenopausal or permanently sterilized (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy) (according to MHRA guidance, see references). 14.History of active substance or alcohol abuse within the last year 15.Evidence of severe retinopathy (e.g. cytomegalovirus retinitis, macular degeneration) or clinically relevant ophthalmological disorder (due to diabetes mellitus or hypertension) 16.Thyroid dysfunction(clinical symptoms of thyroid hyper- or hypofunction) not adequately controlled 17.Patients tested positively with TgAb (autoantibodies to thyroglobulin) and / or TPOAb (autoantibodies to thyroid peroxidase) at screening 18.History of major organ transplantation 19.History of uncontrolled severe seizure disorder 20.Leukocytopenia at the time of screening 21.Thrombocytopenia at the time of screening 22.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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of AOP2014 vs. HU in terms of disease response rate in both HU naïve and currently treated patients, diagnosed with Polycythemia Vera. ;Secondary Objective: Efficacy in the two treatment arms, safety, QoL and change of JAK-2 allelic burden will be analyzed, using the secondary endpoints outlined, to provide a more comprehensive picture on AOP2014 compared to HU in patients with PV.;Primary end point(s): • Primary efficacy endpoint: - Disease response rate at 12 months defined as hematocrit <45% without phlebotomy (at least 3 months since last phlebotomy), platelets 400 x109/l , leukocytes 10x 109 /L (all three lab parameters measured by blinded central lab), and normal spleen size (by imaging, central, blinded assessment) ;Timepoint(s) of evaluation of this end point: Month 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Secondary efficacy endpoints - Disease response rate at 6 months, based on hematological parameters only, defined as hematocrit <45% without phlebotomy (at least 3 months since last phlebotomy), platelets <400 x109/L, leukocytes <10 x109/L (all three lab parameters measured by blinded central lab) for the formal interim analysis, - Disease response rate at 6 months, defined as hematocrit <45% without phlebotomy (at least 3 months since last phlebotomy), platelets <400 x109/L, leukocytes <10 x 109/L (all three lab parameters measured by blinded central lab), and normal spleen size (by imaging, local ultrasonography measurement). - Disease response rates at months 3 and 9 months (spleen size measurements and hematological parameters coming from local measurements) - Time to first disease response - Disease response duration - Number of phlebotomies performed (per protocol, a phlebotomy has to be performed any time the patient’s hematocrit is higher than 45%) - Hematocrit change from baseline to last patient visit - Leukocytes change from baseline to last patient visit - Platelets change from baseline to last patient visit - Erythrocytes change from baseline to last patient visit - Spleen size from baseline to last patient visit - Disease-related symptoms (microvascular disturbances, pruritus, headache) - • Safety evaluation - Incidence, causality and intensity of adverse events according to common terminology criteria for adverse events (CTCAE 4.0) - Events leading to dose reduction or permanent treatment discontinuation. Adverse events of special interest (see section 7.3.9) • Quality of Life (EQ-5D) • Change of JAK-2 allelic burden over time;Timepoint(s) of evaluation of this end point: Months 3,6,9 and change over time as well as time to response | — |
Countries
Austria, Belgium, Bulgaria, Czech Republic, France, Germany, Hungary, Italy, Poland, Romania, Russian Federation, Slovakia, Spain, Ukraine
Contacts
Public Contactmichael.zoerer@aoporphan.com
AOP Orphan Pharmaceuticals AG
Outcome results
None listed