Paroxysmal Nocturnal Hemoglobinuria
Conditions
Interventions
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
Sponsors
Wynne Weston-Davies
Eligibility
Inclusion 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. 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.
Exclusion criteria
Exclusion criteria: 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Long term safety and efficacy of rVA576 (Coversin) therapy assessed by AEs, SAEs, Standard Lab tests and ECG results. Standard safety lab tests are provided in the study protocol (section 5.7.8). Lab tests are as follows; Haematology & Chemistry including LDH, Full blood count (FBC), creatinine & urinalysis (including pregnancy testing) Additional central lab samples are collected these are: Total C5, CH50, unbound rVA576 (Coversin) blood level (PK), LTB4 & ADA. Local safety and central samples would ensure clinicians can determine if any untoward lab results are available for patient safety. Adverse Event (AE) Any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of the study medication, whether or not considered related to the study medication. Serious adverse event (SAE) Any untoward medical occurrence or effect that at any dose results in: •Results in death •Is life-threatening •Requires inpatient hospitalization or prolongation of existing hospitalization •Results in persistent or significant disability/incapacity •Is a congenital anomaly/birth defect. Routine ECG should be performed at entry and then annually during the study. The ECG traces (using Limb lead or 12 lead ECG depending on what is available at site) will be reviewed, signed, and dated by a physician and he/she will record on the trace whether the ECG is normal or abnormal and if deemed abnormal, whether the abnormality is clinically significant (CS) or not clinically significant (NCS). [Time Frame: 4 years ] [] [] . [] [] [ ] | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Proportion of subjects with thrombotic and haemolytic event free status during each 3 month time period since the start of the study. [1. Time Frame: 12 weeks ] 2. Time to thrombotic or haemolytic event since joining this study. [ 2. [ Time Frame: 4 years ]] 3. 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. [ Time Frame: 4 years ]] 4.Time to first transfusion since joining the study. [ 4. [ Time Frame: 4 years ]] 5. 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. [ 5. [ Time Frame: 12 weeks ]] 6. Proportion of subjects with serum Lactate Dehydrogenase (LDH) 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. [ 6. [ Time Frame: 12 weeks ]] 7. Proportion of subjects with median serum Lactate Dehydrogenase (LDH) 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. [ 7. [ Time Frame: 4 years ]] 8. 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. [ 8. [ Time Frame: 3 monthly ]] 9. 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 [ 9. [ Time Frame: 12 weeks ]] 10. Proportion of patients experiencing Major Adverse Vascular Events (MAVE) over the entire period of the study. [ 10. [ Time Frame: 4 years ]] 11.Time to first Major Adverse Vascular Event (MAVE) for each subject since joining the study. [ 11. [ Time Frame: 4 years ]] 12.. Number of Major Adv | — |
Countries
Sri Lanka
Contacts
Public ContactDr Senani Williams
Consultant Hematologist
Outcome results
None listed