* The purpose of this study is to to determine the safety profile of long-termCoversin treatment.* To observe the long term safety and efficacy of Coversin over periods in excess of 6 months* To assess the long term patient acceptability of Coversin…
ID
Source
Brief title
Condition
- Haemolyses and related conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Safety and Efficacy Endpoints:
Long term safety of rVA576 (Coversin) as assessed by SAEs, AEs, vital signs,
immunogenicity assessments, results of appropriate standard laboratory tests
(clinical chemistry, haematology, coagulation, urinalysis, and ADA) and results
of electrocardiograms (ECGs).
Secondary outcome
PNH Secondary:
1.Proportion of subjects with thrombotic and haemolytic event-free status
during each 3 month time period since the start of the study.
2.Time to thrombotic or haemolytic event since the start of the study.
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, with analysis of i) subjects who were transfusion-dependent when
they started receiving rVA576 (Coversin), ii) subjects who
weretransfusion-independent when they started receiving rVA576 (Coversin), and
iii) all subjects, and further stratification of these proportions by a)
patients who were complement inhibitor-naïve prior to treatment with rVA576
(Coversin), and b) patients who received treatment with another
complement inhibitor before switching to rVA576 (Coversin).
4.Time to first transfusion since joining the study.
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.
6.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.
7.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.
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. With
baseline for CAPSTONE (AK580) defined as the haemoglobin value
at which they received their qualifying transfusion (the set point) or for
COBALT (AK579) and CONSENT (AK578) the haemoglobin value at which
patients entered those trials. With separate analysis of subjects who were i)
transfusion-independent prior to receiving rVA576 (Coversin)
and remain transfusion-independent and ii) transfusion-dependent prior to
receiving rVA576 (Coversin).
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. With baseline haemoglobin defined as for the
previous secondary endpoint (#8). With separate analysis of subjects who were
i) transfusion-independent prior to receiving rVA576
(Coversin) and remain transfusion-independent and ii) transfusion-dependent
prior to receiving rVA576 (Coversin).
10.Proportion of patients experiencing Major Adverse Vascular Events (MAVE)
over the entire period of the study.
11.Time to first Major Adverse Vascular Event (MAVE) for each subject since
joining the study.
12.Number of Major Adverse Vascular Events (MAVE) over the entire period of the
study.
aHUS Secondary:
aHUS Secondary:
1.Proportion of subjects with Normal Platelet count [defined as Platelet count
* 150 x109/L] at each 3-month time point since the start of the
study and over the entire period of the study.
2.Proportion of subjects entering study with complete TMA response who continue
to exhibit complete TMA response with preserved renal
function, defined as hematologic normalization (platelet count *150 X 109/L and
LDH * ULN) and preservation of kidney function (<25%
increase in SCr from baseline of previous study), during each 3-month time
period since the start of this study.
3.Proportion of subjects with complete TMA response with improved renal
function defined as normalization of haematological parameters
(normalisation of platelet count and LDH*ULN) and * 25% decrease in SCr from
baseline of previous study during each 3-month time period
since the start of the study.
4.Proportion of subjects who exhibit haematological normalisation (platelet
count *150 X 109/L and LDH * ULN) during each 3-month time
period since the start of this study.
5.Proportion of subjects with improvement in renal function defined as a
decrease in SCr over three consecutive measurements from baseline of
previous study without the need for dialysis even if not within the normal
range.
6.Proportion of subjects who are TMA event-free during each 3-month time period
since the start of the study.
7.Platelet mean count change at each 3-month time period since the start of the
study.
8.Quality of Life measures from baseline at 3 monthly intervals up to the end
of study in FACIT-F instrument and the EQ-5D-5L instrument.
Additional Endpoints:
*PK and PD parameters during treatment.
Background summary
PNH and aHUS are serious acquired blood diseases in which a person's own blood
cells are not protected against a part of our body*s immune system called the
complement system.
Coversin is a small protein that inhibits one of the complement factors in the
complement system that is responsible for damaging your own cells without
affecting other parts of the complement system. It may help to reduce the
damage to your blood cells that occurs in PNH and aHUS and may reduce the
symptoms of the diseases.
Study objective
* The purpose of this study is to to determine the safety profile of
long-termCoversin treatment.
* To observe the long term safety and efficacy of Coversin over periods in
excess of 6 months
* To assess the long term patient acceptability of Coversin using the EORTC
QLQ-C30 and the EQ-5D-5L instruments and the Sponsor non validated questionnaire
* To observe the changes, if any, in the production of anti-drug antibodies
(ADA) and whether such antibodies are, or become, neutralising
* To assess the effects, if any, on any changes in formulation or drug delivery
that may be introduced during the study period
Study design
Open-label, non-comparative, observational.
Intervention
Daily subcutanous administration of Coversin.
Study burden and risks
While using complement inhibitor, patients should be constantly alert for
meningitis symptoms.
Quality of life questionnaries have to be completed at start, after 3, 6,
9,12,18, 24, 30, 36 months and at the end of study.
Patients have to use adequeate contraceptive precautions.
Pregnancy test for women of childbearing potential must be done monthly and
till 90 days after the last dose.
During all visits blood samples will be collected.
Daily self-injections subcutaneously. It treatment is successful, the daily
subcutaneous adminstration continues indefinately.
Wimpole Street 75-76
London W1G 9RT
GB
Wimpole Street 75-76
London W1G 9RT
GB
Listed location countries
Age
Inclusion criteria
1) Patients 18 years and above successfully 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 total 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. Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of amenorrhea and considered sterile if they 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 >50kg.
7) Received appropriate prophylaxis against Neisseria meningitidis infection, by both immunisation and continuous or intermittent antibiotics.
8) 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 the current protocol in the clinical judgement of the investigator and sponsor.
2) Patient is unwilling to complete the Quaity of Life instruments and diary card
3) Evidence of active meningococcal infection (swab testing not required)
4) On concurrent treatment with another complement inhibitor
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 period.
6) If male, the subject intends to donate sperm during this study or for 90 days after last dose.
7) Failure to satisfy the Investigator of fitness to participate for any reason or condition which, in the opinion of the investigator, cold increase the subject's risk from participating in the study or confound
the outcome of the study.
8) Use of prohibited medication (e.g. eculizumab (Soliris®)
9) The subject has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within one year prior to screening.
10) Participation in other clinical trials with investigational product.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-004129-18-NL |
| CCMO | NL61226.091.17 |