A STUDY TO ASSESS THE SAFETY AND EFFICACY OF RVA576 IN PATIENTS WITH PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA (PNH)
- Conditions
- -D595 Paroxysmal nocturnal haemoglobinuria [Marchiafava-Micheli]Paroxysmal nocturnal haemoglobinuria [Marchiafava-Micheli]D595
- Registration Number
- PER-039-18
- Lead Sponsor
- Akari Therapeutics Plc,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 0
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 four episodes of transfusion of whole blood or PRBC during the 12 months prior to entering the observation period (Part 1), with a minimum of four units in total, and a minimum of one unit 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.
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.
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 <20 x 109/L OR (b) neutrophils < 0.5 x 109/L
3. Patients with a platelet count of ≤ 70 x 109/L
4. Patients with known or suspected acquired somatic mutations affecting the bone marrow (e.g. acute myeloid leukaemia) which may be associated with PNH
5. History of recurrent bacterial infections or suspicion of active bacterial infections requiring antibiotic therapy
6. Chemotherapy within 3 months of screening visit
7. Planned or actual pregnancy or breast feeding (females)
8. Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom)
9. Unresolved N. meningitidis infection. Patients who have positive nasal or throat swabs must be excluded until eradication of the organism by antibiotic treatment has been confirmed by repeat swabbing and growth testing
10. Patients who are not willing to receive adequate immunisation against N. meningitidis unless, in the opinion of the investigator, the risks of delaying therapy outweigh the risks of developing a meningococcal infection
11. Impaired hepatic function (bilirubin > 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 .
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:The primary endpoint will be assessed at the end of Part 2<br>Measure:Haemoglobin stabilisation rate<br>Haemoglobin greater than the set point for each patient defined during the pre-study randomization period, and the avoidance of PRBC transfusions during the treatment period.<br><br>Timepoints:180 Dias<br>
- Secondary Outcome Measures
Name Time Method <br>Outcome name:Safety, known and potential risks for patients.<br>Measure:Number of units of PRBC transfused from baseline Day 1 (start of Part 2) to Day 180<br>• Percentage of patients who achieve transfusion avoidance from baseline Day 1(start of Part 2) to Day 180<br>• Change in QoL score using FACIT-F from baseline Day 1 (start of Part 2) to Day 180<br>• AUC [LDH] from baseline Day 1 (start of Part 2) to Day 180<br>• CH50 levels from baseline Day 1 (start of Part 2) to Day 180<br><br>Timepoints:180 dias<br>