An extension study on rVA576 (Coversin) for Patients with PNH and aHUS who received benefit from their initial study

• Register: EUCTR
• Last refreshed on: 13 July 2020
• Main ID: EUCTR2016-004129-18-GB
• Date of registration: 21/12/2016
• Prospective Registration: Yes
• Primary sponsor: Akari Therapeutics Plc
• Public title: An extension study on rVA576 (Coversin) for Patients with PNH and aHUS who received benefit from their initial study
• Scientific title: CONSERVE: rVA576 (Coversin) Long Term Safety and Efficacy Surveillance Study
• Date of first enrolment: 17/03/2017
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004129-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, France, Germany, Kazakhstan, Lithuania, Netherlands, Poland, Sri Lanka, United Kingdom

Contacts

• Name: Medical Director
• Affiliation: Akari Therapeutics Plc

• Name: Medical Director
• Affiliation: Akari Therapeutics Plc

Key inclusion & exclusion criteria

Inclusion criteria:
1)Patients 18 years and above successfully treated with rVA576 (Coversin) under other Akari clinical trial protocols and wish to remain
on rVA576 (Coversin)at the conclusion of that trial.
2)In the opinion of the treating responsible clinician patient is receiving clinical benefit from continued treatment with study drug.
3)Evidence of sustained total 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. Women are considered post-menopausal and not of childbearing potential if they have had 12 months of
amenorrhea and considered sterile if they 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 >50kg .
7)Received appropriate prophylaxis against Neisseria meningitidis infection, by both immunisation and continuous or intermittent antibiotics
8)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.

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 42
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion criteria:
1)Patient experienced any safety event in the previous study protocol, which puts the patient at unacceptable risk in the current protocol in the clinical judgement of the investigator and sponsor.
2)Patient is unwilling to complete the Quaity of Life instruments and diary card.
3)Active meningococcal infection (section 4.3.2 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 period.
6)If male, the subject intends to donate sperm during this study or for 90 days after last dose.
7)Failure to satisfy the Investigator of fitness to participate for any reason or any condition which, in the opinion of the investigator, could increase the subject's risk from 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 within one year prior to screening.
10)Participation in other clinical trials with investigational product.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS)
MedDRA version: 21.1 Level: PT Classification code 10018932 Term: Haemolytic uraemic syndrome System Organ Class: 10005329 - Blood and lymphatic system disorders
MedDRA version: 21.1 Level: PT Classification code 10034042 Term: Paroxysmal nocturnal haemoglobinuria System Organ Class: 10038359 - Renal and urinary disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Code: rVA576
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: rVA576
Current Sponsor code: rVA576
Other descriptive name: rVA576
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 18-

Primary Outcome(s)

Primary end point(s): Primary Efficacy Endpoints:
Long term safety of rVA576 (Coversin) as assessed by SAEs, AEs, vital signs, immunogenicity assessments, results of appropriate standard laboratory tests (clinical chemistry, haematology, coagulation, urinalysis, and ADA).

Secondary Objective: Not applicable

Timepoint(s) of evaluation of this end point: 3, 6, 9, 12 months and every 6 monthly thereafter until the end of the study

Main Objective: The objectives of the study are:
1)To observe the long term safety and efficacy of rVA576 (Coversin) over periods in excess of 6 months
2)To assess the long term patient acceptability of rVA576 (Coversin) using the EORTC QLQ-C30 and the EQ-5D-5L instruments
3)To observe the changes, if any, in the production of anti-drug antibodies (ADA) and whether such antibodies are, or become, neutralising
4)To assess the effects, if any, on any changes in formulation or drug delivery that may be introduced during the study period

Secondary Outcome(s)

Secondary end point(s): Secondary Efficacy Endpoints:
1)Thrombotic and haemolytic event free survival at 3, 6, 9 and 12months and 6 monthly thereafter from the start of the long term safety and efficacy study.
2)Reduction in requirement for blood or blood product transfusion compared to pre-rVA576 (Coversin) treatment over a similar period if data are available (for complement inhibitor naïve patients).
3)Reduction in requirement for blood or blood product transfusion compared to pre-rVA576 (Coversin) treatment over a similar period (for patients who received treatment with another complement inhibitor before switching to rVA576 (Coversin).
4)Non-inferiority in requirement for blood or blood product transfusion compared to pre-rVA576 (Coversin) treatment over a similar period for patients who received treatment with another complement inhibitor before switching to rVA576 (Coversin). For example there should be no increase in transfusion requests for 3 months post-switch compared to 3 months pre-switch.
5)Quality of life using the EORTC QLQ-C30 and the EQ-5D-5L instruments at 3, 6, 9 and12 months and at each clinic visit thereafter.

Timepoint(s) of evaluation of this end point: 3, 6, 9, 12 months and 6 monthly thereafter until the end of the study

Secondary ID(s)

AK581

Source(s) of Monetary Support

Akari Therapeutics Plc

Ethics review

Status: Approved
Approval date: 17/03/2017
Contact: