Primary Objective: To evaluate the immunogenicity of N9-GPKey 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 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 during routine prophylaxis
* FIX trough levels
* Adverse Events (AEs) and Serious Adverse Events (SAEs)
* General safety endpoints including laboratory parameters, physical
examination and vital signs
Background summary
The rationale for this extension trial is to investigate the safety and
efficacy of long-term treatment with N9-GP in haemophilia B patients. This is
in accordance with the EMA guideline. 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 efficacy of N9-GP by the surrogate marker for efficacy, FIX
activity
* To evaluate general safety of N9-GP
Study design
The trial is designed as an open, non-randomised, multi-national trial with the
purpose of evaluating safety and clinical efficacy of treatment of bleeding
episodes and for long-term prophylaxis with N9-GP.
A minimum of 50-100 patients are planned to complete the trial. The trial will
have one treatment arm with four different treatment regimens: three
prophylaxis treatment regimens and one on-demand treatment.
After completion of either the pivotal trial (Paradigm2), or the surgery trial
(Paradigm3) patients may be offered to continue with prophylaxis or on-demand
treatment in this phase 3b extension trial until no later than 31 March 2014.
Patients eligible for the trial will receive N9-GP as prophylaxis or as
on-demand treatment. The choice of treatment is agreed between the patient and
the Investigator and can be changed through the trial. However, with
Substantial Amendment no 17 change of treatment regime is no longer possible
for patients treated on demand or with the low weekly prophylaxis dose (10
U/kg).
In most cases, N9-GP is administered at home except when patients on
prophylaxis are attending a visit at the clinic. In this case, N9-GP is
administered at the clinic to allow for both pre- and post-dose blood samples
and assessments. The patients will initially attend the clinic every 3 months,
reducing to every 6 months after Visit 5.
Intervention
Weekly injections with N9-GP (prophylaxis), every second week 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
Alphen a/d Rijn 2408 AV
NL
Flemingweg 18
Alphen a/d Rijn 2408 AV
NL
Listed location countries
Age
Inclusion criteria
Previous participation in Paradigm2 or Paradigm3
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
* 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)
* Any disease (liver, kidney, inflammatory and mental disorders included) or condition which, according to the Investigator*s judgement, could imply a potential hazard to the patient, interfere with trial participation, or interfere with trial outcome
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 | EUCTR2010-023072-17-NL |
| ClinicalTrials.gov | NCT01395810 |
| CCMO | NL35226.041.11 |