Paroxysmal Nocturnal Haemoglobinuria (PNH) MedDRA version: 21.1 Level: PT Classification code 10034042 Term: Paroxysmal nocturnal haemoglobinuria System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Code: rVA576
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: NA
Current Sponsor code: rVA576
Concentration unit: mg milligram(s)
Concentration type: equal
Concentra
Sponsors
Akari Therapeutics Plc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing to give informed consent to treatment with rVA576 2. Diagnosed with paroxysmal nocturnal haemoglobinuria (PNH) confirmed by flow cytometry 3. Have not received any complement inhibitor within the 4 months prior to screening 4. = 18 years of age at the time of screening 5. Weight =50kg 6. Complete transfusion medical history for 12 months prior to entering the observation period and definitely prior to receiving the qualifying transfusion must be available to the patient's investigator and be verifiable by the Sponsor or its representative. 7. Transfusion dependent and has received at least 4 episodes of transfusion of whole blood or PRBC during the 12 months prior to entering the observation period (Part 1), with a minimum of 4 units in total, and a minimum of 1unit at each transfusion episode. 8. LDH =1.5 x the ULN per the local lab. 9. Willing to receive appropriate prophylaxis against Neisseria meningitidis infection by both immunisation and continuous or intermittent antibiotics. 10. Willing to avoid prohibited medications such as other complement inhibitors and chemotherapeutic agents 11. Patients must agree to avoid pregnancy and fathering children from the time of signing the Informed Consent Form until 90 days after the last dose of rVA576. Permitted contraceptive methods that are =99% effective in preventing pregnancy should be communicated to trial patients and their understanding confirmed. Two approved methods of highly effective contraception must be used by the patient and their partner. 12. Patients who are on erythropoietin and/or immunosuppressant treatment should be on stable doses for at least 6 months prior to entering the observation period (Part 1). The dose of these drugs should not be changed during Part 1 or 2. 13. Patients who are taking systemic corticosteroids should be on a stable dose for at least 4 weeks prior entering the observation period (Part 1). If corticosteroids, either topical or systemic, are being taken for reasons unconnected with the target condition (e.g. for allergic rhino-conjunctivitis) they may be adjusted as clinically appropriate but otherwise should remain at constant dosage. 14. Patients on anticoagulant therapy should be well-controlled prior to entry into the observation period (Part 1) and control should be maintained as long as anticoagulation is considered to be an appropriate therapy. A change of up to 20% to a previously stable anticoagulant therapy is permitted 15. Patients taking iron and/or folic acid supplements should be on a stable dose for at least 4 weeks prior to entering the observation period (Part 1). The dose of iron and/or folic acid supplements should not be adjusted during the trial. PART 2 Inclusion Criteria 1. Complete transfusion medical history for 12 months prior to receiving qualifying transfusion must be available to the patient's investigator and be verifiable by the Sponsor or its representative. 2. A qualifying transfusion is mandatory during Part 1 with Hb=70g/L (7g/dL) with or without symptoms or >70g/L (7g/dL) to =90g/L (9g/dL) with symptoms. 3. The qualifying transfusion during the observation period (Part 1) requiring a minimum of 1 unit of PRBC. The quantity of PRBC to be transfused will be according to the algorithm in the protocol. 4. Patient must be within 15g/L (1.5g/dL) of the mean haemoglobin from the previous 12 months 5. Will have a minimum of 1 sign or 1 symptom of PNH from the following list: fra
Exclusion criteria
Exclusion criteria: 1. Patients whose mean haemoglobin level over the previous 12 months prior to screening was greater than 105 g/L (10.5g/dL). 2. Severe bone marrow failure as manifested by (a) a peripheral blood reticulocyte count 1.5 x ULN and AST/ALT >2.5 x ULN) unless, in the opinion of the investigator, the risks of delaying therapy outweigh the risks of treatment in the presence of impaired hepatic function. 12. Patients with a glomerular filtration rate (GFR) of <30mL/min/1.73m2 unless, in the opinion of the investigator, the risks of delaying therapy outweigh the risks of treatment in the presence of impaired renal function. 13. Participation in other clinical trials within 4 weeks of signing the consent form. 14. 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 psoriatic arthritis. 15. Any other systemic disorders that could interfere with the evaluation of the study treatment. 16. Failure to comply with protocol requirements 17. Known Hepatitis B or Hepatitis C, as per medical history. PART 2 Exclusion Criteria 1. Presence or suspicion of active bacterial infection requiring antibiotic therapy in the opinion of the Investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the efficacy of rVA576 plus SoC compared to SoC in patients with uncontrolled haemolysis due to paroxysmal nocturnal haemoglobinuria (PNH).;Secondary Objective: To assess the safety and tolerability of rVA576 in treatment of patients with PNH.;Primary end point(s): The primary endpoint is haemoglobin stabilisation rate defined as haemoglobin greater than the set point for each patient defined during the pre-study randomisation period, and the avoidance of PRBC transfusions during the treatment period. ;Timepoint(s) of evaluation of this end point: The primary endpoint will be assessed at the end of Part 2. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Number of units of PRBC transfused from baseline Day 1 (start of Part 2) to Day 180 •Percentage of patients who achieve transfusion avoidance from baseline Day 1(start of Part 2) to Day 180 •Change in QoL score using FACIT-F from baseline Day 1 (start of Part 2) to Day 180 •AUC [LDH] from baseline Day 1 (start of Part 2) to Day 180 •CH50 levels from baseline Day 1 (start of Part 2) to Day 180 ;Timepoint(s) of evaluation of this end point: Day 180 | — |
Countries
Ecuador, Kazakhstan, Lithuania, Peru, Romania, Sri Lanka, Turkey
Contacts
Public ContactWynne Weston-Davies
Akari Therapeutics Plc.
Outcome results
None listed