treating paroxysmal nocturnal haemoglobinuria patients with rva576

Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)

Summary: rva576 for patients with paroxysmal nocturnal hemoglobinuria (pnh).

rva576, a small protein complement c5 inhibitor which prevents the cleavage of c5 by c5 convertase into c5a and c5b, will be used in an open label, non-comparative clinical trial in patients with pnh. patients will be treated with rva576 by daily subcutaneous injection in order to determine the safety and efficacy of the drug in these circumstances. if satisfactory control of the pnh is achieved, and at the discretion of the principal investigator (pi), patients will have the option of remaining on rva576 and being entered into the long term follow-up study.

Eligibility criteria:
inclusion criteria: 1. willing to give informed consent to treatment with rva576 2. diagnosed with paroxysmal nocturnal haemoglobinuria (pnh) 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 7. transfusion dependent 8. ldh ≥1.5 x the uln 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. 13. patients who are taking systemic corticosteroids should be on a stable dose for at least 4 weeks. 14. patients on anticoagulant therapy should be well-controlled prior to entry. 15. patients taking iron and/or folic acid supplements should be on a stable dose for at least 4 weeks 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 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. chemotherapy within 3 months of screening visit 6. history of recurrent bacterial infections or suspicion of active bacterial infections requiring antibiotic therapy 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. 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 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. 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