Clinical trial NCT03829449: rVA576 (Coversin) Long Term Safety and Efficacy Surveillance Study
Official title: CONSERVE: rVA576 (Coversin) Long Term Safety and Efficacy Surveillance Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Lead sponsor: AKARI Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-02-04
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, non-comparative
Primary purpose: TREATMENT

Brief summary: Long term management of patients with complement related diseases including Paroxysmal Nocturnal Haemoglobinuria and Atypical Haemolytic Uraemic Syndrome

Detailed description: Patients with diseases requiring complement inhibition who have previously taken part in Akari clinical trials and who wish to continue to receive rVA576 (Coversin) after their active participation in the parent trial has completed and patients treated under compassionate use or named patient arrangements who wish to continue on rVA576 (Coversin) therapy

Eligibility criteria: Inclusion Criteria:

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. In the opinion of the treating responsible clinician patient is receiving clinical benefit from continued treatment with study drug.
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 ≥50-100kg
7. Willing to receive appropriate prophylaxis against Neisseria meningitidis infection, by both immunisation 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.

Exclusion Criteria:

1. Patient experienced any safety event in the previous study protocol, which puts the patient at unacceptable risk in 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 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
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.

Primary outcomes:
measure: Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results.
timeFrame: On entry and every 3 months thereafter, for the duration of the study (approximately 3 years and 5 months)
Secondary outcomes:
measure: Proportion of Subjects With Thrombotic and Haemolytic Event Free Status During Each 3month Time Period Since the Start of the Study.
timeFrame: On entry and every 3 months thereafter, for the duration of the study (approximately 3 years and 5 months)
measure: Time to Thrombotic or Haemolytic Event Since Joining This Study.
timeFrame: Approximately 3 years and 5 months
measure: Proportion of Subjects Who Require PRBC Transfusion During Each 3-month Period Since the Start of the Study and Over the Entire Period of the Study
timeFrame: On entry and every 3 months thereafter, for the duration of the study (approximately 3 years and 5 months)
measure: Time to First Transfusion Since Joining the Study.
timeFrame: approximately 3 years and 5 months
measure: Proportion of Subjects With no Adverse Change in Overall Scores of Quality of Life Using the EORTC QLQ-C30, the EQ-5D-5L and FACIT-F Instruments at Each 3-month Time Period Since the Start of the Study.
timeFrame: Every 3 months up to 39 months
measure: Proportion of Subjects With Serum Lactate Dehydrogenase (LDH) <1.8, >1.8 to 2.4, >2.4 to 3, and >3 Times the Upper Limit of Normal (ULN) at Each 3-month Time Period Since the Start of the Study.
timeFrame: 12 weeks
measure: Proportion of Subjects With Median Serum Lactate Dehydrogenase (LDH) <1.8, >1.8 to 2.4, >2.4 to 3, and >3 Times the Upper Limit of Normal (ULN) Over the Entire Duration of the Study.
timeFrame: Approximately 3 years and 5 months
measure: Proportion of Transfusion-independent Subjects at Each 3-month Time Point, With Haemoglobin (g/L) Above the Baseline Haemoglobin Value They Had at the Start of the Trial From Which They Entered CONSERVE
timeFrame: Baseline and every 3 months up to 39 months
measure: Proportion of Transfusion-independent Subjects Over the Entire Duration of the Study With Mean Haemoglobin (g/L) Above the Baseline Haemoglobin Value They Had at the Start of the Trial From Which They Entered CONSERVE
timeFrame: Approximately 3 years and 5 months
measure: Proportion of Patients Experiencing Major Adverse Vascular Events (MAVE) Over the Entire Period of the Study.
timeFrame: Approximately 3 years and 5 months
measure: Time to First Major Adverse Vascular Event (MAVE) for Each Subject Since Joining the Study.
timeFrame: Approximately 3 years and 5 months
measure: Number of Major Adverse Vascular Events (MAVE) Over the Entire Period of the Study.
timeFrame: Approximately 3 years and 5 months
Other outcomes:
Locations:
city: Warsaw
country: Poland
facility: Instytut Hematologii i Transfuzjologii
Study officials:
affiliation: AKARI Therapeutics
name: Wynne Weston Davies
role: STUDY_DIRECTOR
References: