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
- Conditions
- Polycythemia VeraMedDRA version: 17.1Level: LLTClassification code 10036061Term: Polycythemia veraSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2012-005259-18-BE
- Lead Sponsor
- AOP Orphan Pharmaceuticals AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 256
1.18 years or older
2. Diagnosis of Polycythemia Vera according to the WHO 2008 criteria (Barbui et al, 2011 - Appendix 1) 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 frequent need of phlebotomy (more than one phlebotomy within last three months prior entering the study, while each of these phlebotomies was performed to reduce Hct level from >45%, or if one phlebotomy was not able to reduce Hct level to <45% for the next three months following phlebotomy)
- progressive splenomegaly (de novo appearance of a palpable spleen, or appearance of the symptoms, related to the enlarged spleen, e.g. pain, early satiety etc., with confirmed size increase)
- platelet counts greater than 1000 x10^9/L (for two measurements within one week)
- leukocytosis (WBC>10 x10^9/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, see section 3.1.1)
- total HU treatment duration shorter than three years
- no documented resistance or intolerance as defined by modified Barosi et al, 2009 criteria(Appendix 2)
5. Hospital Anxiety and Depression Scale (HADS) score 0-7 on both subscales
6. Patients with 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 56
1. Any systematic cytoreduction for PV in the medical history prior study entry with 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 manifestations, 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) and/or splenectomy in the medical history
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 contraception. Note: 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 and / or TPOAb at screening
18. History of major organ transplantation
19. History of uncontrolled severe seizure disorder
20. Leukocytopenia (leukocytes below the lower limit of normal) at the time of screening
21. Thrombocytopenia (platelets below the lower limit of normal) 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
With regard to acetylsalicylic acid, the following contraindications are known for low dose acetylsalicylic acid: active peptic ulceration or history of peptic ulceration, hemophilia, hypersensitivity to acetylsalicylic acid or any other NSAIDs, including those in whom attacks of asthma, angioedema, urticaria, rhinitis have been precipitated by acetylsalicylic acid or any other NSAID, hypersensitivity to any of the other constituents. If any of the contraindications are observed, the patient may still participate in the study without being administered acetylsalicylic acid.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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:<br>- Disease response rate at 12 months defined as hematocrit <45% without phlebotomy (at least 3 months since last phlebotomy), platelets <400 x 10^9/L, leukocytes <10 x 10^9/L (all three lab parameters measured by blinded central lab), and normal spleen size (by imaging, central, blinded assessment)<br>;Timepoint(s) of evaluation of this end point: Month 12
- Secondary Outcome Measures
Name Time Method