Paroxysmal Nocturnal Hemoglobinuria
Conditions
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
Interventions
DRUGrVA576
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).
Sponsors
AKARI Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label, non-comparative
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | On entry and every 3 months thereafter, for the duration of the study (approximately 3 years and 5 months) | To determine the safety profile of long-term rVA576 (Coversin) treatment as assessed by AEs, SAEs, Standard Lab tests and ECG results. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Thrombotic or Haemolytic Event Since Joining This Study. | Approximately 3 years and 5 months | 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 | On entry and every 3 months thereafter, for the duration of the study (approximately 3 years and 5 months) | 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. | approximately 3 years and 5 months | 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. | Every 3 months up to 39 months | 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. | 12 weeks | 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 Thrombotic and Haemolytic Event Free Status During Each 3month Time Period Since the Start of the Study. | On entry and every 3 months thereafter, for the duration of the study (approximately 3 years and 5 months) | Thrombotic and Haemolytic Events will include, but are not limited to, the following: haemolytic anaemia, thrombocytopenia, red blood cell haemolysis indicated by dark urine, Budd-Chiara syndrome, any other thrombotic or haemolytic event deemed to be associated with PNH. A haemolytic event will be defined as a rise in LDH or other biochemical evidence of haemolysis accompanied by an increase in symptoms and/or frank haemoglobinuria. Increased symptoms without objective haematological or biochemical evidence of haemolysis will not be counted as haemolytic events. In addition, the following signs and symptoms may be reviewed and classified as Thrombotic/Haemolytic events if appropriate: Acute kidney failure, Hypertension, Myocardial infarction, Stroke, Lung complications, Seizure, Coma, Premature death. |
| 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 | Baseline and every 3 months up to 39 months | 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 | Approximately 3 years and 5 months | 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. | Approximately 3 years and 5 months | 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. | Approximately 3 years and 5 months | 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. | Approximately 3 years and 5 months | Number of Major Adverse Vascular Events (MAVE) over the entire period 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. | Approximately 3 years and 5 months | 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. |
Countries
Poland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| rVA576 Coversin 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 for up to 4 years. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | rVA576 Coversin |
|---|---|
| Age, Continuous | 39 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment Argentina | 1 participants |
| Region of Enrollment Lithuania | 2 participants |
| Region of Enrollment Netherlands | 1 participants |
| Region of Enrollment Poland | 5 participants |
| Region of Enrollment Sri Lanka | 4 participants |
| Region of Enrollment United Kingdom | 2 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 14 / 15 |
| serious Total, serious adverse events | 3 / 15 |
Outcome results
Primary
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.
Time frame: On entry and every 3 months thereafter, for the duration of the study (approximately 3 years and 5 months)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Adverse Events | 14 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Serious Adverse Events | 3 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant hemoglobin (low) | 7 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant hematocrit (low) | 6 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant MCH (high) | 4 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant MCV (high) | 3 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant RBC (low) | 6 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant reticulocytes (high) | 4 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant basophils (low) | 1 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant eosinophils (low) | 1 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant neutrophils (low) | 1 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant platelets (low) | 1 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant reticulocytes (low) | 2 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant WBC (low) | 1 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant ALT (high) | 3 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant AST (high) | 6 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant creatine kinase (high) | 2 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant creatinine (high) | 6 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant direct bilirubin (high) | 5 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant total bilirubin (high) | 7 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant gamma glutamyl transpeptidase (GGT) (high) | 2 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant LDH (high) | 10 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant potassium (high) | 1 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant urea (high) | 2 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant potassium (low) | 1 Participants |
| rVA576 | Long Term Safety and Efficacy of rVA576 (Coversin) Therapy Assessed by AEs, SAEs, Standard Lab Tests and ECG Results. | Clinically significant ECG | 1 Participants |
Secondary
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.
Time frame: Approximately 3 years and 5 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rVA576 | Number of Major Adverse Vascular Events (MAVE) Over the Entire Period of the Study. | 0 events |
Secondary
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 frame: Approximately 3 years and 5 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rVA576 | Proportion of Patients Experiencing Major Adverse Vascular Events (MAVE) Over the Entire Period of the Study. | 0 Participants |
Secondary
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 frame: On entry and every 3 months thereafter, for the duration of the study (approximately 3 years and 5 months)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rVA576 | 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 | 0 - 3 Months | 3 Participants |
| rVA576 | 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 | >3 - 6 Months | 2 Participants |
| rVA576 | 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 | >6 - 9 Months | 2 Participants |
| rVA576 | 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 | >9 - 12 Months | 3 Participants |
| rVA576 | 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 | >12 - 15 Months | 3 Participants |
| rVA576 | 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 | >15 - 18 Months | 0 Participants |
| rVA576 | 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 | >18 - 21 Months | 0 Participants |
| rVA576 | 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 | >21 - 24 Months | 1 Participants |
| rVA576 | 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 | >24 - 27 Months | 1 Participants |
| rVA576 | 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 | >27 - 30 Months | 1 Participants |
| rVA576 | 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 | >30 Months | 0 Participants |
| rVA576 | 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 | Entire Study | 4 Participants |
Secondary
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.
Time frame: Approximately 3 years and 5 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rVA576 | 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. | 4 Participants |
Secondary
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.
Time frame: Every 3 months up to 39 months
Population: Not all participants completed the self-reported questionnaires at all timepoints
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rVA576 | 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. | 0 - 3 Months - EORTC QLQ-C30 | 9 Participants |
| rVA576 | 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. | >3 - 6 Months - EORTC QLQ-C30 | 8 Participants |
| rVA576 | 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. | >6 - 9 Months - EORTC QLQ-C30 | 9 Participants |
| rVA576 | 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. | >9 - 12 Months - EORTC QLQ-C30 | 6 Participants |
| rVA576 | 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. | >12 - 15 Months - EORTC QLQ-C30 | 0 Participants |
| rVA576 | 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. | >15 - 18 Months - EORTC QLQ-C30 | 4 Participants |
| rVA576 | 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. | >18 - 21 Months - EORTC QLQ-C30 | 2 Participants |
| rVA576 | 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. | >21 - 24 Months - EORTC QLQ-C30 | 5 Participants |
| rVA576 | 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. | >24 - 27 Months - EORTC QLQ-C30 | 3 Participants |
| rVA576 | 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. | >27 - 30 Months - EORTC QLQ-C30 | 4 Participants |
| rVA576 | 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. | >30 - 33 Months - EORTC QLQ-C30 | 2 Participants |
| rVA576 | 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. | >33 - 36 Months - EORTC QLQ-C30 | 1 Participants |
| rVA576 | 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. | >36 - 39 Months - EORTC QLQ-C30 | 2 Participants |
| rVA576 | 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. | 0 - 3 Months - EQ-5D-5L | 7 Participants |
| rVA576 | 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. | >3 - 6 Months - EQ-5D-5L | 6 Participants |
| rVA576 | 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. | >6 - 9 Months - EQ-5D-5L | 8 Participants |
| rVA576 | 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. | >9 - 12 Months - EQ-5D-5L | 4 Participants |
| rVA576 | 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. | >12 - 15 Months - EQ-5D-5L | 1 Participants |
| rVA576 | 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. | >15 - 18 Months - EQ-5D-5L | 5 Participants |
| rVA576 | 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. | >18 - 21 Months - EQ-5D-5L | 2 Participants |
| rVA576 | 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. | >21 - 24 Months - EQ-5D-5L | 2 Participants |
| rVA576 | 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. | >24 - 27 Months - EQ-5D-5L | 3 Participants |
| rVA576 | 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. | >27 - 30 Months - EQ-5D-5L | 3 Participants |
| rVA576 | 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. | >30 - 33 Months - EQ-5D-5L | 2 Participants |
| rVA576 | 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. | >33 - 36 Months - EQ-5D-5L | 2 Participants |
| rVA576 | 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. | >36 - 39 Months - EQ-5D-5L | 2 Participants |
| rVA576 | 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. | 0 - 3 Months - FACIT-F | 0 Participants |
| rVA576 | 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. | >3 - 6 Months - FACIT-F | 1 Participants |
| rVA576 | 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. | >6 - 9 Months - FACIT-F | 0 Participants |
| rVA576 | 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. | >9 - 12 Months - FACIT-F | 0 Participants |
| rVA576 | 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. | >12 - 15 Months - FACIT-F | 0 Participants |
| rVA576 | 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. | >15 - 18 Months - FACIT-F | 0 Participants |
| rVA576 | 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. | >18 - 21 Months - FACIT-F | 0 Participants |
| rVA576 | 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. | >21 - 24 Months - FACIT-F | 0 Participants |
| rVA576 | 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. | >24 - 27 Months - FACIT-F | 0 Participants |
| rVA576 | 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. | >27 - 30 Months - FACIT-F | 0 Participants |
| rVA576 | 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. | >30 - 33 Months - FACIT-F | 0 Participants |
| rVA576 | 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. | >33 - 36 Months - FACIT-F | 0 Participants |
| rVA576 | 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. | >36 - 39 Months - FACIT-F | 0 Participants |
Secondary
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.
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rVA576 | 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. | 3 Participants |
Secondary
Proportion of Subjects With Thrombotic and Haemolytic Event Free Status During Each 3month Time Period Since the Start of the Study.
Thrombotic and Haemolytic Events will include, but are not limited to, the following: haemolytic anaemia, thrombocytopenia, red blood cell haemolysis indicated by dark urine, Budd-Chiara syndrome, any other thrombotic or haemolytic event deemed to be associated with PNH. A haemolytic event will be defined as a rise in LDH or other biochemical evidence of haemolysis accompanied by an increase in symptoms and/or frank haemoglobinuria. Increased symptoms without objective haematological or biochemical evidence of haemolysis will not be counted as haemolytic events. In addition, the following signs and symptoms may be reviewed and classified as Thrombotic/Haemolytic events if appropriate: Acute kidney failure, Hypertension, Myocardial infarction, Stroke, Lung complications, Seizure, Coma, Premature death.
Time frame: On entry and every 3 months thereafter, for the duration of the study (approximately 3 years and 5 months)
Population: Data are not available for all 15 participants at every 3-month interval due to the early termination of the trial. The proportion of subjects with thrombotic or haemolytic event free status in each 3-month interval is calculated based on the actual number of participants analysed at each 3-month interval.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rVA576 | 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 event free status: 0 - 3 Months | 15 Participants |
| rVA576 | 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 event free status: >3 - 6 Months | 15 Participants |
| rVA576 | 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 event free status: >6 - 9 Months | 11 Participants |
| rVA576 | 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 event free status: >9 - 12 Months | 10 Participants |
| rVA576 | 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 event free status: >12 - 15 Months | 10 Participants |
| rVA576 | 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 event free status: >15 - 18 Months | 10 Participants |
| rVA576 | 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 event free status: >18 - 21 Months | 8 Participants |
| rVA576 | 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 event free status: >21 - 24 Months | 7 Participants |
| rVA576 | 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 event free status: >24 - 27 Months | 6 Participants |
| rVA576 | 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 event free status: >27 - 30 Months | 6 Participants |
| rVA576 | 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 event free status: >30 Months | 5 Participants |
| rVA576 | 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 haemolytic event free status: 0 - 3 Months | 13 Participants |
| rVA576 | 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 haemolytic event free status: >3 - 6 Months | 11 Participants |
| rVA576 | 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 haemolytic event free status: >6 - 9 Months | 9 Participants |
| rVA576 | 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 haemolytic event free status: >9 - 12 Months | 9 Participants |
| rVA576 | 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 haemolytic event free status: >12 - 15 Months | 10 Participants |
| rVA576 | 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 haemolytic event free status: >15 - 18 Months | 10 Participants |
| rVA576 | 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 haemolytic event free status: >18 - 21 Months | 8 Participants |
| rVA576 | 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 haemolytic event free status: >21 - 24 Months | 7 Participants |
| rVA576 | 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 haemolytic event free status: >24 - 27 Months | 6 Participants |
| rVA576 | 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 haemolytic event free status: >27 - 30 Months | 6 Participants |
| rVA576 | 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 haemolytic event free status: >30 Months | 5 Participants |
Secondary
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
Time frame: Baseline and every 3 months up to 39 months
Population: Total number of subjects analyzed at each timepoint is specified.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rVA576 | 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 | Baseline | 11 Participants |
| rVA576 | 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 | Month 3 | 4 Participants |
| rVA576 | 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 | Month 6 | 4 Participants |
| rVA576 | 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 | Month 9 | 3 Participants |
| rVA576 | 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 | Month 12 | 4 Participants |
| rVA576 | 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 | Month 15 | 0 Participants |
| rVA576 | 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 | Month 18 | 3 Participants |
| rVA576 | 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 | Month 21 | 1 Participants |
| rVA576 | 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 | Month 24 | 3 Participants |
| rVA576 | 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 | Month 27 | 1 Participants |
| rVA576 | 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 | Month 30 | 3 Participants |
| rVA576 | 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 | Month 33 | 1 Participants |
| rVA576 | 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 | Month 36 | 1 Participants |
| rVA576 | 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 | Month 39 | 1 Participants |
Secondary
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
Time frame: Approximately 3 years and 5 months
Population: Total number of subjects analyzed with post-baseline values is specified.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rVA576 | 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 | Baseline | 11 Participants |
| rVA576 | 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 | Overall Post-Baseline Mean Haemoglobin | 4 Participants |
Secondary
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.
Time frame: Approximately 3 years and 5 months
Population: There were no Major Adverse Vascular Events (MAVEs) reported during the entire period of the study.
Secondary
Time to First Transfusion Since Joining the Study.
Time to first transfusion since joining the study.
Time frame: approximately 3 years and 5 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| rVA576 | Time to First Transfusion Since Joining the Study. | 30.5 days |
Secondary
Time to Thrombotic or Haemolytic Event Since Joining This Study.
Time to thrombotic or haemolytic event since joining this study.
Time frame: Approximately 3 years and 5 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rVA576 | Time to Thrombotic or Haemolytic Event Since Joining This Study. | 113.0 days since first dose | Standard Deviation 80.61 |