To determine the safety and efficacy of coversin in the treatment of patients with PNH resistant to eculizumab.
ID
Source
Brief title
Condition
- Haemolyses and related conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Significant reduction in mean serum LDH from Day 0 to Day 28
Secondary outcome
Change in LDH from Day 0 (pre-dose) at monthly intervals after Day 28
Change in proportion of PNH clone Day 0 * Day 90
Change in mean Hb Day 0 * Day 90
Change in mean Hp Day 0 * Day 90
Change in FACIT score Day 0 * Day 28 - Day 90 - Day 180
Change in EORTC QLQ C30 score Day 0 * Day 28 - Day 90 * Day 180
Background summary
PNH is a serious acquired blood disorder in which the own blood cells are not
protected against complement. Under the influence of activated complement, the
blood cells are lysed with severe disease symptoms as a result.
The only registered agent for the treatment of PNH is eculizumab (Soliris).
Eculizumab acts by binding complement factor C5 that is circulating in the
blood and thus prevents activation of the complement. The blood cells survive
and the disease symptoms are reduced.
A small number of PNH patients have a polymorphism in C5 which prevents
eculizumab from binding to C5. Eculizumab does not work in these patients.
Coversin is a new agent that also binds complement factor C5, but at a
different part of the C5 protein compared to eculizumab. In the laboratory it
has been shown that coversin binding is not influenced by the C5 polymorphism.
Coversin inhibits complement activation in a similar way as eculizumab does.
Coversin has been tested in healthy volunteers and administration of coversin
was shown to be safe. The new product is now being developed for the treatment
of PNH and in particular of PNH patients who are resistant to eculizumab as a
result of a C5 polymorphism.
Study objective
To determine the safety and efficacy of coversin in the treatment of patients
with PNH resistant to eculizumab.
Study design
Open label, non-comparative
Intervention
Daily subcutanous administration of coversin.
Study burden and risks
While using complement inhibitors, patients should be constantly alert for
meningitis symptoms (also applies to standard treatment with eculizumab).
Quality of life questionnaires have to be completed at start, after 28 days,
after three months and after six months.
Patients have to use adequate contraceptive precautions.
During the first 6 months, control visits will take place more often than
usual. Appr. 10-12 extra visits. During all visits blood samples will be
collected
At the start of the treatment, patients are hospitalized for at least two
nights (pharmacokinetics).
Daily self-injections subcutaneously. Upon initiation of treatment, patients
will be instructed how to inject thelselves subcutaneously. If treatment is
successful, the daily subcutaneous administration continues indefinately.
Wimpole Street 76
London (UK) W1G9RT
GB
Wimpole Street 76
London (UK) W1G9RT
GB
Listed location countries
Age
Inclusion criteria
Patients with known paroxysmal nocturnal haemoglobinuria (PNH);LDH *1.5 ULN;Resistance to eculizumab proven by both a recognised C5 polymorphism on genetic screening and complement inhibition on CH50 ELISA of <100% at concentrations of eculizumab in excess of 50µg/mL;Willing to self-inject Coversin daily or to receive daily subcutaneous injections by a home nurse or in a doctor*s office or hospital clinic;Willing to receive appropriate prophylaxis against Neisseria infection by either or both immunisation or continuous or intermittent antibiotics;Males or females taking adequate contraceptive precautions if of childbearing potential, 18 * 80 years of age;Body weight * 50kg and * 100kg ;The patient has provided written informed consent.;Willing to avoid prohibited medications for duration of study (see Exclusion Criteria);Must be counselled regarding the possible reproductive risks of using Coversin and be advised to use an adequate method of contraception pending further data on reproductive toxicology.
Exclusion criteria
Body weight <50kg or > 100kg ;Pregnancy (females);Use of tizanidine (if on ciprofloxacin);Use of eculizumab (Soliris®) should be discontinued before coversin therapy is commenced. Ideally this should be 2 or more weeks before. ;Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom);Failure to satisfy the PI off fitness to participate for any other reason
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-003778-34-NL |
| ClinicalTrials.gov | NCT02591862 |
| CCMO | NL54988.091.15 |