Paroxysmal nocturnal haemoglobinuria (PNH) MedDRA version: 20.0 Level: PT Classification code 10034042 Term: Paroxysmal nocturnal haemoglobinuria System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Sponsors
Akari Therapeutics Plc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with a diagnosis of PNH confirmed by flow cytometry who, in the opinion of the Investigator, would benefit from treatment with a complement C5 inhibitor 2. Aged 18 and above. No upper age limit 3. Males and females of childbearing potential must agree to use an adequate method of contraception. Females will have a negative pregnancy test before entry to the study 4. Body weight =50kg 5. The patient has given voluntary written informed consent 6. Willing to receive immunisation against Neisseria meningitidis and antibiotic prophylaxis in accordance with the local practice of the PI at the trial site. Antibiotic prophylaxis must continue until at least 14 days after the end of complement inhibition by Coversin. 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 9 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 1. Prior use of eculizumab (Soliris®) within 3 months of entry is prohibited 2. Any other drug acting directly on the complement system is prohibited 3. Chemotherapeutic agents within 3 months of enrolment in the study is prohibited 4. Tizanidine, if using ciprofloxacin prophylaxis is prohibited 5.Known sensitivity to the excipients of meningococcal vaccines, ciprofloxacin or any other antibiotic being administered for purposes of meningitis prophylaxis 6. Participation in other clinical trials within 4 weeks of signing the consent form 7. Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom) 8. History of active systemic autoimmune diseases other than the target condition. Dermatologic diseases such as psoriasis will not be a reason for exclusion unless there are associated systemic symptoms such as arthritis 9. Any systemic disorder that could interfere with the evaluation of the study treatment (e.g. severe renal or hepatic disease that in the opinion of the Investigator would affect the outcome of the study or interfere with interpretation of results) 10. Failure to satisfy the investigator of fitness to participate for any other reason or any condition that, in the opinion of the Investigator, could increase the subject's risk by participating in the study or confound the outcome of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objectives of the study are: • To assess the safety and tolerability of Coversin for all patients for the duration of the study. • To assess efficacy of the dosage regimen to reduce haemolysis and control the signs and symptoms thereof, in PNH subjects as manifested by: i. Serum lactic dehydrogenase (LDH) change from baseline (day 1) to day 28 ii. Haemoglobin (Hb) at day 28 and day 90, absolute and change from baseline iii. Number of blood transfusions iv. Quality of Life - EORTC QLQ-C30 at day 1 (baseline), 7, 14, 21, 29, 60 and 90 days v. Quality of Life – EQ-5D-5L at baseline day 1 (baseline) up to day 60 and then at day 90. • To determine whether self-injection by subjects with PNH is well-accepted and the home care nursing supervision period sufficient using a (non validated) questionnaire at day 29 and day 90. ;Secondary Objective: Not applicable; Primary end point(s): Primary Efficacy Endpoint: Reduction in serum LDH to less than or equal to 1.8 times the upper limit of normal (ULN) for the Investigator's reference laboratory or 500 I U/L whichever is the lower from Day 1 (pre-dose) to Day 28 ;Timepoint(s) of evaluation of this end point: Reduction in serum LDH measured on Days 1 (baseline) to Day 28. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints: • Reduction of LDH to Day 28 of 50% or less of the mean of all pre-dose measurements taken within 14 days of commencing Coversin treatment. If only one result is available during that period it should be used. • Reduction in CH50 from Day 1 pre-dose to Days 7, 14, 21, 28, 60 and 90 • Reduction in serum LDH to less than or equal to 1.8 times the upper limit of normal (ULN) for the Investigator’s reference laboratory or 500 I U/L whichever is the lower at Day 60 and at Day 90 • Increase in Hb Day 1 – Day 90 • Change in EORTC QLQ C30 score from Day 1 (baseline) to days 7, 14, 21, 29, 60 and 90 • Change in EQ-5D-5L from baseline Day 1 (baseline) to Day 60 and then at Day 90. Safety Endpoints: •Frequency, type and relationship of AEs and SAEs to treatment. •Out of range laboratory parameters (haematology and chemistry). •Vital signs (blood pressure, body temperature and pulse). •ECG abnormalities pre dose – Day 90 (A resting pre-dose ECG taken within 7 days of first dose will be compared with ECGs taken 1- 6 hours post-dose and at 90 days of treatment with Coversin) •Change in weight or percentage body fat will be noted pre-dose and at Day 90. •Injection site reaction and lymph node inspection. •Anti-coversin antibody production. ; Timepoint(s) of evaluation of this end point: LDH measured from Day 1 (baseline) to Day 28. Reduction in CH50 -Day 1, 7, 14, 21, 28, 60, 90. HB-measured from Day 1 to Day 90. EORTC QLQ C30 measured from Day 1 (baseline) to Days 7, 14, 21, 29, 60 and 90. EQ-5D-5L measured from Day 1 (baseline) to Day 60 and then at Day 90. AEs, SAEs | — |
Countries
United Kingdom
Contacts
Public ContactMedical Director
Akari Therapeutics Plc
Outcome results
None listed