E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diagnosis for Polycythemia Vera as per the WHO or PVSG. |
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E.1.1.1 | Medical condition in easily understood language |
Disease of the bone marrow stem cell coming along with a significant increase in red blood cells. Additionally the amount of platelets and white blood cells may also be increased.
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036061 |
E.1.2 | Term | Polycythemia vera |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Investigation of maximum tolerated dose |
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E.2.2 | Secondary objectives of the trial |
•Safety/Tolerability •Efficacy |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 PV according to either the WHO criteria 2008 or the PSVG criteria plus JAK-2 positivity. 4. Eastern Cooperative Oncology Group performance status ≤ 2 5. 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. |
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E.4 | Principal 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. Previous treatment with Interferon for PV 6. Concurrent treatment with other cytoreductive agents other than Hydroxyurea and investigational agents of any type 7. History of malignant disease, including solid tumours and haematological 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 8. History of severe allergic (like anaphylaxis) or hypersensitivity reactions (like angioedema), any known or suspected intolerance to the investigational product. 9. Use of any investigational drug or participation in an investigational drug study within the last 4 weeks 10. Clinically significant history or known presence of psychiatric disorders, including but not limited to depression, anxiety and sleep disorders 11. Organ transplant, past or planned 12. Inadequate liver function: Serum (total) bilirubin > 2,5 x ULN, 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 to be assessed within 7 days prior to study treatment start) 16. Acute or chronic infections or autoimmune diseases (collagen diseases, polyarthritis, immune thrombocythemia, psoriasis, lupus etc, thyroiditis.)
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E.5 End points |
E.5.1 | Primary end point(s) |
Identification of the maximum tolerated dose (MTD) of the investigational medicinal product. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Determination of safety and tolerability of P1101 in patients with polycythaemia vera. An exploratory analysis of efficacy and biomarker modulation will be also performed. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout the whole study.
Efficacy: The first time after 12 weeks and then every 10 weeks thereafter.
Biomarker: Every 2 weeks until MTD, then 5 times every 2 weeks followed by an optional intensive biomarker blood sampling schedule (6 times in the course of 2 weeks). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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1 year for every patient. Thereafter the patients will be treated with the study medication as long as they will derive a clinical benefit from the treatment with acceptable tolerability. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 17 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |