Back to resultsrVA576 (Coversin) Long Term Safety and Efficacy Surveillance Study (CONSERVE)
Primary Purpose
Paroxysmal Nocturnal Hemoglobinuria
Status
Terminated
Phase
Phase 3
Locations
Poland
Study Type
Interventional
Intervention
rVA576 (Coversin)
Sponsored by
About this trial
This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria
Eligibility Criteria
Inclusion Criteria:
- 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.
- In the opinion of the treating responsible clinician patient is receiving clinical benefit from continued treatment with study drug.
- Evidence of sustained complement inhibition by CH50 assay. .
- 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.
- Males with a childbearing potential partner must agree to use effective contraception consistently OR have had a vasectomy
- Weight ≥50-100kg
- Willing to receive appropriate prophylaxis against Neisseria meningitidis infection, by both immunisation and continuous or intermittent antibiotics
- The patient is willing to give voluntary written informed consent
- The patient is willing in the process of preparation and self-administration of the study drug.
Exclusion Criteria:
- 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.
- Patient is unwilling to complete the Quality of Life instruments and diary card
- Active meningococcal infection (section 4.3.1 for additional information)
- 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).
- 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.
- If male, the subject intends to donate sperm while on the study this study or for 90 days after last dose.
- 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.
- Use of prohibited medication
- The subject has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse.
- Participation in other clinical trials with investigational product.
Sites / Locations
- Instytut Hematologii i Transfuzjologii
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
rVA576 Coversin
Arm Description
The study population will consist of patients who have completed participation in clinical trials under other Akari protocols and who wish to continue to receive rVA576 (Coversin) for up to 4 years.
Outcomes
Primary Outcome Measures
Long term safety and efficacy of rVA576 (Coversin) therapy assessed by AEs, SAEs, Standard Lab tests and ECG results.
To determine the safety profile of long-term rVA576 (Coversin) treatment as assessed by AEs, SAEs, Standard Lab tests and ECG results.
Secondary Outcome Measures
Proportion of subjects with thrombotic and haemolytic event free status during each 3month time period since the start of the study.
Proportion of subjects with thrombotic and haemolytic event free status during each 3month time period since the start of the study.
Time to thrombotic or haemolytic event since joining this study.
Time to thrombotic or haemolytic event since joining this study.
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
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
Time to first transfusion since joining the study.
Time to first transfusion since joining the study.
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.
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.
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.
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.
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.
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.
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
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
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
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
Proportion of patients experiencing Major Adverse Vascular Events (MAVE) over the entire period of the study.
Proportion of patients experiencing Major Adverse Vascular Events (MAVE) over the entire period of the study.
Time to first Major Adverse Vascular Event (MAVE) for each subject since joining the study.
Time to first Major Adverse Vascular Event (MAVE) for each subject since joining the study.
Number of Major Adverse Vascular Events (MAVE) over the entire period of the study.
Number of Major Adverse Vascular Events (MAVE) over the entire period of the study.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03829449
Brief Title
rVA576 (Coversin) Long Term Safety and Efficacy Surveillance Study
Acronym
CONSERVE
Official Title
CONSERVE: rVA576 (Coversin) Long Term Safety and Efficacy Surveillance Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Terminated
Why Stopped
The early termination of this study is a business decision, Akari have made the decision to close their global Phase III PNH program. The decision was not related to any efficacy, safety or clinical concerns regarding Coversin/rVA576.
Study Start Date
March 13, 2017 (Actual)
Primary Completion Date
August 29, 2020 (Actual)
Study Completion Date
August 29, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AKARI Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paroxysmal Nocturnal Hemoglobinuria
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Model Description
Open-label, non-comparative
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
rVA576 Coversin
Arm Type
Experimental
Arm Description
The study population will consist of patients who have completed participation in clinical trials under other Akari protocols and who wish to continue to receive rVA576 (Coversin) for up to 4 years.
Intervention Type
Drug
Intervention Name(s)
rVA576 (Coversin)
Intervention Description
The study population will consist of patients who have completed participation in clinical trials under other Akari protocols and who wish to continue to receive rVA576 (Coversin).
Primary Outcome Measure Information:
Title
Long term safety and efficacy of rVA576 (Coversin) therapy assessed by AEs, SAEs, Standard Lab tests and ECG results.
Description
To determine the safety profile of long-term rVA576 (Coversin) treatment as assessed by AEs, SAEs, Standard Lab tests and ECG results.
Time Frame
4 years
Secondary Outcome Measure Information:
Title
Proportion of subjects with thrombotic and haemolytic event free status during each 3month time period since the start of the study.
Description
Proportion of subjects with thrombotic and haemolytic event free status during each 3month time period since the start of the study.
Time Frame
12 weeks
Title
Time to thrombotic or haemolytic event since joining this study.
Description
Time to thrombotic or haemolytic event since joining this study.
Time Frame
4 years
Title
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
Description
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
Time Frame
4 years
Title
Time to first transfusion since joining the study.
Description
Time to first transfusion since joining the study.
Time Frame
4 years
Title
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.
Description
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.
Time Frame
12 weeks
Title
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.
Description
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.
Time Frame
12 weeks
Title
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.
Description
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.
Time Frame
4 years
Title
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
Description
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
Time Frame
3 monthly
Title
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
Description
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
Time Frame
12 weeks
Title
Proportion of patients experiencing Major Adverse Vascular Events (MAVE) over the entire period of the study.
Description
Proportion of patients experiencing Major Adverse Vascular Events (MAVE) over the entire period of the study.
Time Frame
4 years
Title
Time to first Major Adverse Vascular Event (MAVE) for each subject since joining the study.
Description
Time to first Major Adverse Vascular Event (MAVE) for each subject since joining the study.
Time Frame
4 years
Title
Number of Major Adverse Vascular Events (MAVE) over the entire period of the study.
Description
Number of Major Adverse Vascular Events (MAVE) over the entire period of the study.
Time Frame
4 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
In the opinion of the treating responsible clinician patient is receiving clinical benefit from continued treatment with study drug.
Evidence of sustained complement inhibition by CH50 assay. .
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.
Males with a childbearing potential partner must agree to use effective contraception consistently OR have had a vasectomy
Weight ≥50-100kg
Willing to receive appropriate prophylaxis against Neisseria meningitidis infection, by both immunisation and continuous or intermittent antibiotics
The patient is willing to give voluntary written informed consent
The patient is willing in the process of preparation and self-administration of the study drug.
Exclusion Criteria:
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.
Patient is unwilling to complete the Quality of Life instruments and diary card
Active meningococcal infection (section 4.3.1 for additional information)
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).
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.
If male, the subject intends to donate sperm while on the study this study or for 90 days after last dose.
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.
Use of prohibited medication
The subject has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse.
Participation in other clinical trials with investigational product.
Facility Information:
Facility Name
Instytut Hematologii i Transfuzjologii
City
Warsaw
ZIP/Postal Code
02-776
Country
Poland
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
rVA576 (Coversin) Long Term Safety and Efficacy Surveillance Study
We'll reach out to this number within 24 hrs