Primary objective:- To assess the safety of concizumab given as multiple s.c. doses to subjects with haemophilia ASecondary objectives:- To assess pharmacokinetics of concizumab in subjects with haemophilia A after multiple s.c. doses- To assess…
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint:
- Number of adverse events (AEs) from first trial drug administration (day 1)
to 11 weeks after the first trial product administration.
Secondary outcome
Key secondary endpoints:
- Trough level of concizumab prior to the last subcutaneous dose administration
(day 42).
- Frequency of binding non-neutralizing anti-concizumab antibodies from first
trial drug administration (day 1) to 11 weeks after the first trial product
administration.
Background summary
Current replacement therapy of haemophilia with coagulation factors is hampered
by the fact that these products must be given by intravenous injections. These
injections are known to be painful, difficult, and time consuming for many
patients resulting in delayed treatment or under-treated patients. In addition,
repeated venepuncture is not always possible in very young children. The use of
an implantable venous access device has facilitated prophylaxis in some
children, but is associated with complications such as infections, sepsis, and
venous thrombosis. Therefore, a new therapeutic agent that can be administered
subcutaneously will represent a major improvement in the treatment of
haemophilia patients on prophylaxis.
Study objective
Primary objective:
- To assess the safety of concizumab given as multiple s.c. doses to subjects
with haemophilia A
Secondary objectives:
- To assess pharmacokinetics of concizumab in subjects with haemophilia A after
multiple s.c. doses
- To assess pharmacodynamics of concizumab in subjects with haemophilia A after
multiple s.c. doses
- To assess immunogenicity of concizumab in subjects with haemophilia A
Study design
This phase I trial is designed as a randomised, placebo-controlled, double
blinded within a cohort, multiple dose, dose escalation trial to investigate
safety, pharmacokinetics (PK) and pharmacodynamics (PD) of concizumab when
multiple doses are administered subcutaneously at five different concizumab
dose levels in subjects with haemophilia A without inhibitors.
Five subcutaneous dose levels of concizumab (ranging from 0.25 to 1.5 mg/kg)
are planned to be investigated. Each dose cohort will include 8 haemophilia
subjects to be treated with concizumab/placebo in a 3:1 randomisation (6
subjects treated with concizumab and 2 subjects with placebo). The highest dose
predicted to be given to trial subjects is 1.5 mg/kg.
Between each dose escalation, the population PK model will be updated with PK
data from the previous cohort(s). The dose needed, to achieve the exposure
level intended for the next ascending cohort, will be re-calculated and, if
warranted, doses will be changed as appropriate. Thus, the trial design will
allow for adjustment of dose levels based on an updated population PK model
analysis of the exposure levels.
For each trial subject the trial consists of a minimum of 18 visits, including
one screening visit (visit 1), visits in the dosing period (visit 2 to visit
13), visits in the follow-up period (visit 14 to visit 17) and one End of Trial
(visit 18). A total of 12 doses of concizumab/placebo will be given to each
trial subject over a 42 day period and the trial duration will be approximately
11 weeks. Every trial subject will receive his doses on day 1 and 2 followed by
subsequent every fourth day.
Intervention
Trial products will be administered subcutaneously in the abdominal area under
the surveillance of medically trained trial site staff on day 1 and 2, and
subsequently every 4th day.
Study burden and risks
Occasionally, temporary discomfort, bruising, bleeding or swelling at the site
of the needle insertion for withdrawal of the blood samples may occur. There is
also a very small risk of infection at the place where the needle goes in your
vein. In addition the use of trial product may cause side effects. There may be
a risk of development of blood clots. To minimize the risk of development of
blood clots, the trial will start with a very low dose leading to an exposure,
which is not expected to significantly activate the blood clotting. Secondly,
there may be a risk of development of antibodies against concizumab. Antibody
responses have not been observed in the completed clinical trials, but may
occur after longer exposure periods or when administered to a broader patient
population. There may also be a risk of allergic reactions, including severe
(anaphylactic) reactions, in connection with concizumab administration.
Patients will be monitored closely on the occurrence of possible side effects
or discomforts.
The extent of the burden and the risk associated with participation is
necessary to collect enough data to be able to draw reliable conclusions.
Flemingweg 18
Alphen a/d Rijn 2408 AV
NL
Flemingweg 18
Alphen a/d Rijn 2408 AV
NL
Listed location countries
Age
Inclusion criteria
- Male subjects diagnosed with haemophilia A without inhibitors present at screening and currently treated on-demand.
- Subjects with a baseline level of factor VIII * 2 % based on medical records.
- Age between 18 and 64 years both inclusive, at the time of signing informed consent
- Body weight between 50 and 100 kg, both inclusive.
Exclusion criteria
- Known or suspected hypersensitivity to trial product or related products.
- Platelet count below 50x10^9/L at screening.
- Any clinical signs or known history of thromboembolic events, or subjects considered at high risk of thromboembolic events as judged by the investigator.
- Subjects at increased risk of cardiovascular disease as judged by the investigator.
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 | EUCTR2014-003793-16-NL |
| CCMO | NL53826.018.15 |