E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH) in patients with resistance to Eculizumab due to complement C5 polymorphisms. |
Coversin bij Paroxysmale Nachtelijke Hemoglobinurie (PNH) bij patienten die resistent zijn voor Eculizumab als gevolg van een C5 polymorfisme. |
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E.1.1.1 | Medical condition in easily understood language |
Paroxysmal Nocturnal Haemoglobinuria (PNH) |
Paroxysmale Nachtelijke Hemoglobinurie (PNH) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055629 |
E.1.2 | Term | Paroxysmal nocturnal hemoglobinuria |
E.1.2 | System Organ Class | 100000004857 |
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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 |
Primary Objective: Safety and tolerability of Coversin (rVA576)
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E.2.2 | Secondary objectives of the trial |
Efficacy of Coversin in the treatment of patients with PNH resistant to Eculizumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with known paroxysmal nocturnal haemoglobinuria (PNH) LDH >= 1.5 ULN Resistance to eculizumab proven by both a recognised C5 polymorphism on genetic screening and complement inhibition on CH50 ELISA of < 100 % at concentrations of eculizumab in excess of 50 ug/ml Willing to self-inject Coversin daily of to receive daily subcutaneous injections by a home nurse or in a doctor's office or hospital clinic. Willing to receive appropriate prophylaxes against neisseria infection by either or both immunisation or continuous or intermittent antibiotics. Males or females taking adequate contraceptives precautions if of childbearing potential, 18 - 80 years of age Body weight >=50kg and <=100kg The patient has provided written informed consent Willing to avoid prohibited medications for duration of study Must be counselled regarding the possible reproductive risks of using Coversin and be advised to use an adequate method of contraception pending further data on reproductive toxicology |
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E.4 | Principal exclusion criteria |
Body weight <50kg or >100kg Pregnancy (females) Use of tizanidine (if on ciprofloxacin) Use of eculizumab should be discontinued before coversin therapy is commenced. Ideally this should be 2 of more weeks before. Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom) Failure to satisfy the PI off fitness to participate for any other reason. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Reduction in serum LDH (AUC) from Day 0 to Day 28 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Measurement of change in LDH (AUC) from Day 0 (pre-dose) to Day 28 (AUC) compared with 28 days pre-treatment |
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E.5.2 | Secondary end point(s) |
Measurement of Haemoglobin (Hb), haptoglobin (Hp), Change in LDH, Fatigue level using FACIT instrument, Quality of Life (EORTC QL-C30), PNH RBC clone size, Transfusion requirement, Adverse Events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Measurement of Haemoglobin (Hb) at Day 28 & Day 180 Measurement Haptoglobin (Hp) Day 28 & Day 180 Measurement of Change in LDH from Day 0 (pre-dose) and at monthly intervals up to 1 year (Day 0 (pre-dose), 24 hrs (pre-dose), 48 hrs (pre-dose), Day 2, Day 5, Day 7, 14 and 21, Day 28, 35, 42, 49, Day 60 (weeks 8, 10 and 12), Day 90 (weeks 14, 16, 18, 20 and month 5), Day 180 (months 6, 7, 8, 9, 10 and 11), 1 year (month 12, and every 3 months), End of Study Measurement of Change in proportion of PNH from Day 0 - Day 90 Change in Functional Assessment of Chronic Illness Therapy (FACIT) Score from Day 0 - Day 180 Change in Quality of Life Questionnaire (EORTC QL-C30) Score from Day 0 to Day 180 Number and types of adverse events (AE's) |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | No |
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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |