What is the long term safety and efficacy profile of rVA576 (Coversin) in patients requiring long term complement inhibition due to Paroxysmal nocturnal haemoglobinuria (PNH)?

Phase III trial in patients with uncontrolled hemolysis due to PNH in Sri Lanka who have previously taken part in the CAPSTONE trial (Registered with SLCTR under the registration number SLCTR/2018/033). The study will be conducted at the following institutions under respective specialists to determine the safety profile of long-term rVA576 (Coversin) treatment. The country recruitment target would be 5 patients

Institutions: National Hospital of Sri Lanka, Colombo North Teaching Hospital, Jaffna Teaching Hospital.

Patients may be male or non-pregnant females using adequate methods of contraception if of childbearing potential. Patients who wish to remain on rVA576 (Coversin) at the conclusion of the CAPSTONE trial (registered with SLCTR under registration number SLCTR/2018/033) will enter this open-label, non-comparative study on the same dose and dose frequency (45 mg or 22.5mg twice daily depending on previous dose) as they were receiving at the end of the previous trial (CAPSTONE). The patient will continue on the same dose as CAPSTONE, so this could be either 22.5mg twice daily or 45 mg once daily (AK580). If the Investigator considers that a change in dose or dose frequency is necessary, dosing schedule provided in the study protocol AK581 is followed. A change to an increased dose is mandated by an inadequate response to rVA576 (Coversin), but may also occur at the discretion of the Investigator in consultation with the Sponsor. Duration of the trial would be up to 4 years.

1. Patients 18 years and above treated with rVA576 (Coversin) under other Akari clinical trial protocols and wish to remain on rVA576 (Coversin) at the conclusion of that trial.
2. Patients 18 years and above who have clinical benefit from continued treatment with the study drug as deemed by the treating clinician.
3. Evidence of sustained complement inhibition by CH50 assay.
4. Women of childbearing potential (WOCBP) must agree to use effective contraception consistently throughout the study and have a negative pregnancy test at screening and a negative urine pregnancy test per the schedule of visits. Women cannot donate their eggs. Women are considered post-menopausal and not of childbearing potential if they have had 12 months of amenorrhea or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks previously.
5. Males with a childbearing potential partner must agree to use effective contraception consistently OR have had a vasectomy
6. Weight greater than or equal to 50-100 kg
7. Willing to receive appropriate prophylaxis against Neisseria meningitidis infection, by both immunization and continuous or intermittent antibiotics
8. The patient is willing to give voluntary written informed consent
9. The patient is willing in the process of preparation and self-administration of the study drug.

1. Patient who has experienced any safety event in the previous study protocol, which puts the patient at unacceptable risk in the current protocol as judged by the investigator and sponsor.
2. Patient is unwilling to complete the Quality of Life instruments and diary card
3. Active meningococcal infection (section 4.3.1 of study protocol for additional information)
4. Any other reason for which, in the opinion of the Investigator, it would not be in the interests of the patient to remain on rVA576 (Coversin).
5. If female, the subject is pregnant or lactating or intending to become pregnant before, during, or within 90 days after last dose; or intending to donate ova during such time period.
6. If male, the subject intends to donate sperm while on the study this study or for 90 days after last dose.
7. Failure to satisfy the Investigator of fitness to participate for any other reason or any other condition which, in the opinion of the investigator, could increase the subject's risk by participating in the study or confound the outcome of the study.
8. Use of prohibited medication (e.g. Eculizumab (Soliris), Chemotherapeutic agents, any other drug acting directly on the complement system).
9. The subject has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse.
10. Participation in other clinical trials with investigational product.