Primary Myelofibrosis (grade MF-0 and MF-1) according to the WHO criteria MedDRA version: 17.0 Level: LLT Classification code 10053134 Term: Osteomyelofibrosis 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 Pr
Sponsors
Medizinische Universtät Wien, Universitätsklinik für Innere Medizin I
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent obtained prior to any study specific screening activities and able to comply with this protocol. 2. Patients age =18 years 3. Confirmed diagnosis of primary myelofibrosis (grade MF-0 and MF-1) according to the WHO criteria (2008). Including either newly diagnosed Interferon naive patients or patients pre-treated with Pegasys® or PegIntron®, who had stable disease for the previous 3 months. 4. If female of childbearing potential – have a negative urine pregnancy test result within 7 days prior to the scheduled first application of investigational product and agree to employ adequate birth control measures for the duration of the study. 5. Eastern Cooperative Oncology Group performance status = 2. 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 1. Diagnosis of any other myeloproliferative disorder 2. Any clinically significant illness or surgery within 4 weeks prior to dosing 3. Systemic infections, e.g. hepatitis B, hepatitis C, or HIV at screening 4. Uncontrolled hypertension (systolic > 150 mmHg and diastolic > 100 mmHg, or clinically significant (i.e. active) cardiovascular disease: CVA/stroke (= 3 months prior to enrolment), myocardial infarction (= 3 months prior to enrolment), significant coronary artery stenosis, unstable angina, New York Heart Association (NYHA) Class 2 or greater Congestive heart failure, or serious cardiac arrhythmia requiring medication. 5. History of malignant disease, including solid tumours (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) and haematological malignancies within the last 3 years 6. History of severe allergic (like anaphylaxis) or hypersensitivity reactions (like angioedema), any known or suspected intolerance to the investigational product 7. Use of any investigational drug or participation in any investigational drug study within the last 4 weeks 8. Clinically significant history or known presence of psychiatric disorders, including but not limited to depression, anxiety and sleep disorders 9. HADS score equal to or above 11 on either or both of the subscales (Appendix 3) 10. Any risk of suicide at screening or previous suicide attempts 11. Organ transplant, past or planned 12. Inadequate liver function defined by serum (total) bilirubin > 2,5 x ULN and/or AST and ALT > 2,5 x ULN 13. Clinically significant ECG findings 14. History of renal disease requiring haemodialysis or seizure disorder requiring anticonvulsant therapy 15. Pregnant or lactating females (pregnancy test in fertile women to be assessed within 7 days prior to study treatment start) 16. Acute or chronic infections or autoimmune diseases (collagen diseases, polyarthritis, immune thrombocythemia, thyroiditis, psoriasis, lupus nephritis or any other autoimmune disorder) 17. Advanced primary Myelofibrosis (> Grade 2) 18. Clinically relevant pulmonary infiltrates, pneumonia, and pneumonitis at screening 19. Any significant morbidity or abnormality which may interfere with the study participation 20. History of active substance or alcohol abuse within the last year 21. Evidence of severe retinopathy (e.g. cytomegalovirus retinitis, macular degeneration) or clinically relevant ophthalmological disorder (due to diabetes mellitus or hypertension) 22. Thyroid dysfunction not adequately controlled 23. Patients tested positively with TgAb and / or TPOAb at screening 24. History of uncontrolled severe seizure disorder 25. Leukocytopenia at the time of screening 26. Thrombocytopenia at the time of screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To evaluate quality of life, frequency of disease related events, confirmatory surrogate response parameter, safety observations and dose response correlations. ; Main Objective: To evaluate the efficacy of novel Pegylated-Pro Interferon a-2b formulation in terms of response rate in both, Interferon naive and pretreated patients with early primary myelofibrosis (MF-0 to MF-1). The favourable pharmacokinetic profile of AOP2014 suggests possible dose reduction and/or treatment interval prolongation options, which, at preserved efficacy, may improve the tolerability of IFN a treatment. ; Primary end point(s): • Haematological response rate according to IWG-MRT criteria1 (platelets =100 x 109/l and < UNL (upper normal limit) neutrophils =1 x 109/l and < UNL, < 2% immature myeloid cells • LDH serum level = 300 IU/L (all lab parameters measured by blinded central lab) • Spleen size vs. baseline (preferably volumetric measurement by Sono or MRI) ;Timepoint(s) of evaluation of this end point: after 6 months of the treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: after 6 months of the treatment; Secondary end point(s): • Quality of life Assessment through EORTC QLQ-C30 and MPN-SAF TSS questionnaires • Number of Disease related signs and symptoms within vs 6 month pre-treatment period • Maintenance or improvement of Molecular Response analysed in peripheral blood granulocytes. CR: Eradication of pre-existing abnormality. PR: =50% decrease in allele burden (partial response applies only to patients with at least 20% mutant allele burden et baseline) • Bone marrow histology if routinely available • Monitoring of Surrogate Response Parameters such as inflammation parameters • Maintenance of prognosis evolution assessed according to DIPSS | — |
Countries
Austria
Contacts
Public ContactMedical Information
AOP ORPHAN PHARMACEUTICALS AG
Outcome results
None listed