4159 Explorer™3 safety, PK and PD of concizumab in haemophilia A
Research type
Research Study
Full title
A multi-centre, randomised, placebo controlled, double blinded, multiple dose trial investigating safety, pharmacokinetics and pharmacodynamics of concizumab administered subcutaneously to haemophilia A subjects
IRAS ID
182401
Contact name
Pratima Chowdary
Contact email
Sponsor organisation
Novo Nordisk A/S
Eudract number
2014-003793-16
Duration of Study in the UK
1 years, 9 months, 0 days
Research summary
The study is designed to investigate a new drug called concizumab (the study drug) for potential treatment in patients with severe haemophilia A, which is an inherited life threatening bleeding disorder. The drug has a different way of working in that it blocks the natural anticlotting pathway (called the tissue factor inhibitor pathway) to make the pro-clotting pathway stronger and this promotes the development of normal clots which then stops
bleeding. Importantly the drug can be given subcutaneously (s.c.) (under the skin) unlike medications currently in use which need to be injected into a vein.The major aim of the study is to understand if the drug is safe when multiple doses are given subcutaneously (s.c.) (under the skin) at five different dose levels (ranging from 0.25 to 1.5 mg/kg) in subjects with haemophilia A.
This will be measured by looking at the number of adverse events (any untoward medical events that occur that may or may not be related to the study drug) that are experienced by the patients from the first dose until the end of the trial.
The secondary aims are:
to develop an understanding of how the body handles the drug – how it is absorbed by the body and then broken down or eliminated (pharmacokinetics)
to assess how the drug exerts its effects in the body (pharmacodynamics)
to examine whether the immune system will react to the concizumab i.e. by producing proteins called antibodies. If the immune system reacts to a drug, the antibodies produced can sometimes stop the drug from working.The study is placebo controlled. This means that some subjects will be dosed with concizumab whilst others will receive a placebo. Placebo is a preparation that contains none of the study drug, but appears similar to the study drug. The allocation of treatment will be randomised in an interactive voice response system (IVRS). This means that the decision about whether a patient receives concizumab or placebo will be done in a random way by a computer (much like flipping a coin). The randomisation is blinded which means that neither the patients nor the study staff will know which treatment the patient has been allocated to. This will be done in a 3:1 fashion i.e. there will be 6 patients treated with concizumab and 2 treated with placebo in every dosing group.
After each dose level a safety committee of experts specifically appointed for this purpose will look at all the data collected and decide if it is safe for the next dose level group to open.
The trial consists of a minimum of 18 visits per patient including:
one screening visit (where it will be determined if patients meet the inclusion and exclusion criteria and are able to continue in the trial),
12 visits in the dosing period,
4 visits in the follow-up period
an End of Trial visit.During the visits patients will have a number of assessments performed (e.g. physical examinations, vital signs), blood samples will be taken and they will be dosed with the trial product. A total of 12 doses will be scheduled over a 42 day period. The trial duration will be approximately 11 weeks.
It is anticipated that 40-45 male haemophilia A patients without inhibitors (antibodies that reduce the effect of Factor VIII in the blood) currently treated “on-demand” (i.e. just treated when they experience a bleed) will enter the trial. Subjects will have moderate to severe
haemophilia A (baseline Factor VIII level of ≤2%), be aged 18-64 years of age and weigh between 50-100kg. They must have no history of thromboembolic (blood clotting) events, not have an increased risk of cardiovascular events and have a normal platelet (a blood component) count.REC name
London - Bloomsbury Research Ethics Committee
REC reference
15/LO/1074
Date of REC Opinion
28 Jul 2015
REC opinion
Further Information Favourable Opinion