Home » Trials » SLCTR/2020/005


CONSERVE: rVA576 (Coversin) Long Term Safety and Efficacy Surveillance Study

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SLCTR Registration Number

SLCTR/2020/005


Date of Registration

04 Feb 2020

The date of last modification

Feb 04, 2020



Application Summary


Scientific Title of Trial

CONSERVE: rVA576 (Coversin) Long Term Safety and Efficacy Surveillance Study


Public Title of Trial

Long Term Safety and Efficacy of Coversin in Patients With Paroxysmal Nocturnal Haemoglobinuria (PNH)


Disease or Health Condition(s) Studied

Paroxysmal Nocturnal Hemoglobinuria


Scientific Acronym

CONSERVE


Public Acronym

CONSERVE


Brief title

rVA576 (Coversin) Long Term Safety and Efficacy Surveillance Study


Universal Trial Number

U1111-1244-6223


Any other number(s) assigned to the trial and issuing authority

US registry: ClinicalTrials.gov Identifier: NCT03829449 EU clinical trial register: EudraCT number 2016-004129-18, ERC number P/183/08/2019


Trial Details


What is the research question being addressed?

What is the long term safety and efficacy profile of rVA576 (Coversin) in patients requiring long term complement inhibition due to Paroxysmal nocturnal haemoglobinuria (PNH)?


Type of study

Interventional


Study design

Allocation

Single arm study


Masking

Masking not used


Control

Uncontrolled


Assignment

Single


Purpose

Treatment


Study Phase

Phase 3


Intervention(s) planned

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). The study will be conducted at the following institutions under respective specialists to determine the safety profile of long-term rVA576 (Coversin) treatment. The country recruitment target would be 5 patients

Institutions: National Hospital of Sri Lanka, Colombo North Teaching Hospital, Jaffna Teaching Hospital.

Patients may be male or non-pregnant females using adequate methods of contraception if of childbearing potential. Patients who wish to remain on rVA576 (Coversin) at the conclusion of the CAPSTONE trial (registered with SLCTR under registration number SLCTR/2018/033) will enter this open-label, non-comparative study on the same dose and dose frequency (45 mg or 22.5mg twice daily depending on previous dose) as they were receiving at the end of the previous trial (CAPSTONE). The patient will continue on the same dose as CAPSTONE, so this could be either 22.5mg twice daily or 45 mg once daily (AK580). If the Investigator considers that a change in dose or dose frequency is necessary, dosing schedule provided in the study protocol AK581 is followed. A change to an increased dose is mandated by an inadequate response to rVA576 (Coversin), but may also occur at the discretion of the Investigator in consultation with the Sponsor. Duration of the trial would be up to 4 years.


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

  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.


Primary outcome(s)

1.

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

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Secondary outcome(s)

1.
  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.
  1. Time to thrombotic or haemolytic event since joining this study.
[
  1. [ Time Frame: 4 years ]
]
3.
  1. 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
[
  1. [ Time Frame: 4 years ]
]
4.

4.Time to first transfusion since joining the study.

[
  1. [ Time Frame: 4 years ]
]
5.
  1. 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.
[
  1. [ Time Frame: 12 weeks ]
]
6.
  1. 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.
[
  1. [ Time Frame: 12 weeks ]
]
7.
  1. 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.
[
  1. [ Time Frame: 4 years ]
]
8.
  1. 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.
[
  1. [ Time Frame: 3 monthly ]
]
9.
  1. 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
[
  1. [ Time Frame: 12 weeks ]
]
10.
  1. Proportion of patients experiencing Major Adverse Vascular Events (MAVE) over the entire period of the study.
[
  1. [ Time Frame: 4 years ]
]
11.

11.Time to first Major Adverse Vascular Event (MAVE) for each subject since joining the study.

[
  1. [ Time Frame: 4 years ]
]
12.

12.. Number of Major Adverse Vascular Events (MAVE) over the entire period of the study.

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  1. [ Time Frame: 4 years ]
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Target number/sample size

5


Countries of recruitment

Sri Lanka


Anticipated start date

2020-02-06


Anticipated end date

2024-03-12


Date of first enrollment


Date of study completion


Recruitment status

Pending


Funding source

Akari Therapeutics Plc. 75-76 Wimpole Street, London, W1G 9RT, UK


Regulatory approvals

Approved by National Medicines Regulatory Authority, on 18 Nov 2019 under the reference number NMRA/CTRD/P4 CTM/020/2019



State of Ethics Review Approval


Status

Approved


Date of Approval

2019-09-10


Approval number

P/183/08/2019


Details of Ethics Review Committee

Name: University of Kelaniya
Institutional Address:Ethics Review Committee, Faculty of Medicine, University of Kelaniya, Ragama
Telephone:011-2961267
Email: ercmed@kln.ac.lk

Contact & Sponsor Information


Contact person for Scientific Queries/Principal Investigator

Dr Senani Williams
Consultant Hematologist
Department of Pathology Faculty of Medicine University of Kelaniya
+94 2961000 Ext 192
+94 77 9548740

senaniw@kln.ac.lk

Contact Person for Public Queries

Dr Senani Williams
Consultant Hematologist
Department of Pathology Faculty of Medicine University of Kelaniya
+94 2961000 Ext 192
+94 77 9548740

senaniw@kln.ac.lk


Primary study sponsor/organization

Wynne Weston-Davies

Akari Therapeutics Plc. 75-76 Wimpole Street London, W1G 9RT United Kingdom
+44(0)2080040268

wynne.weston-davies@akaritx.com

Secondary study sponsor (If any)







Trial Completion details


Do the investigators plan to share identified individual clinical trial participant-level data (IPD)?

No


IPD sharing plan description

NA


Study protocol available

Yes


Protocol version and date

Version 3.0, 11 January 2019


Protocol URL


Results summary available

No


Date of posting results


Date of study completion


Final sample size


Date of first publication


Link to results


Brief summary of results