Primary Objective: To evaluate the immunogenicity of N9-GP.Key Secondary Objectives: * To evaluate clinical efficacy of haemostasis (treatment of bleeding episodes) of N9-GP.* To evaluate clinical efficacy of N9-GP in long term bleeding prophylaxis…
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoint: Incidence of inhibitory antibodies against FIX defined as
titre *0.6 BU.
Secondary outcome
Key Secondary Endpoints:
* Haemostatic effect of N9-GP when used for treatment of bleeding episodes,
assessed as success/failure based on a four-point scale for haemostatic
response (excellent, good, moderate and poor) by counting excellent and good as
success and moderate and poor as failure
* Number of bleeding episodes per patient during routine prophylaxis
* FIX trough levels
* Adverse Events (AEs) and Serious Adverse Events (SAEs)
* Host Cell Proteins (HCP)-antibodies
* General safety endpoints including laboratory parameters, physical
examination and vital signs
Background summary
The rationale for this pivotal trial is to investigate the safety and efficacy,
including PK of N9-GP when used for treatment and prophylaxis of bleeding
episodes in haemophilia B patients. Based on clinical and non-clinical studies
conducted, N9-GP is a promising drug candidate for prevention/prophylaxis and
on-demand treatment of bleedings in haemophilia B patients. The completed phase
1 trial showed a mean t* of 93 hours which is approximately 5 times higher than
commercially available FIX concentrates.
Study objective
Primary Objective: To evaluate the immunogenicity of N9-GP.
Key Secondary Objectives:
* To evaluate clinical efficacy of haemostasis (treatment of bleeding episodes)
of N9-GP.
* To evaluate clinical efficacy of N9-GP in long term bleeding prophylaxis
(number of bleeding episodes during prophylaxis)
* To evaluate the efficacy of N9-GP by the surrogate marker for efficacy, FIX
activity
* To evaluate general safety of N9-GP
Study design
The trial is a single-blind, multi-national trial evaluating safety,
pharmacokinetics and clinical efficacy of N9-GP when used for treatment of
bleeding episodes and for long-term prophylaxis. The trial therefore has
characteristics of Phase 1, 2 and 3 (pharmacokinetics, safety and efficacy).
Single-blind in this trial means that patients on prophylaxis do not know
whether they are allocated to a low or high dose arm.
A minimum of 60 patients must complete the trial. The patients can be included
in either the prophylaxis or the on-demand arm. In the prophylaxis arms the
patients will be randomised to either a high dose arm or the low dose arm. Each
patient in the prophylaxis arms must attain 50 exposure days to N9-GP through
the trial.
Two PK profiles from 15 of the patients in the prophylaxis arms must be
obtained during the trial and these PK sessions will be carried out with three
different lots of N9-GP.
The duration of the trial for each patient in the prophylaxis arms will be 52
weeks, and for patients in the on-demand arm it will be 28 weeks.
Intervention
Weekly injections with N9-GP (prophylaxis) or injections with N9-GP at the
first signs of a bleeding episode (on-demand).
Study burden and risks
It's possible that bloodwithdrawals or injections with N9-GP can cause
haemorrhages or discomfort. There is also a very small chance of infection on
the injection site. The patient could also experience side effects from N9-GP.
There is a risk of development of antibodies against N9-GP and/or FIX that
could decrease the effectiveness of future treatments with FIX products.
Flemingweg 18
2408 AV Alphen a/d Rijn
NL
Flemingweg 18
2408 AV Alphen a/d Rijn
NL
Listed location countries
Age
Inclusion criteria
* Male patients, aged 13-70 years, with moderately severe or severe congenital haemophilia B with a FIX activity *2% according to medical records
NB: In The Netherlands only patients aged 18-70 years will be included
* History of at least 150 exposure days to other FIX products
* Patients currently treated on-demand with at least 6 bleeding episodes during the last 12 months or at least 3 bleeding episodes during the last 6 months, or patients currently on prophylaxis
Exclusion criteria
* Known history of FIX inhibitors based on existing medical records, laboratory report reviews and patient and LAR interviews
* Current FIX inhibitors *0.6 BU (central laboratory)
* HIV positive with a viral load *400,000 copies/mL and/or CD4+ lymphocyte count *200/*L
* Congenital or acquired coagulation disorders other than haemophilia B
* Previous arterial thrombotic events (e.g. myocardial infarction and intracranial thrombosis) or previous deep venous thrombosis or pulmonary embolism (as defined by available medical records)
* Platelet count <50.000 platelets/*l at screening (local laboratory)
* ALT >3 times the upper limit of normal reference ranges at screening (central laboratory)
* Creatinine level *1.5 times above upper normal limit at screening (central laboratory)
* Immune modulating or chemotherapeutic medication
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 | EUCTR2010-023069-24-NL |
| ClinicalTrials.gov | NCT01333111 |
| CCMO | NL35181.041.11 |