Co-Primary Objectives* To evaluate the immunogenicity of N8-GP in previously treated patients with haemophilia A* To evaluate the clinical efficacy of N8-GP in bleeding prohylaxis (number of bleeds during prophylaxis)Secondary Objectives* To…
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Co-Primary Endpoints
* The Incidence rate of FVIII-inhibitors *0.6 BU
* Annualised bleeding rate for patients receiving prophylaxis treatment
Secondary outcome
Secondary Endpoints
* Haemostatic effect of N8-GP when used for treatment of bleeds, assessed on a
four-point scale for haemostatic response (excellent, good, moderate and none)
by counting excellent and good as success and moderate and none as failure
* Consumption of N8-GP (number of infusions and U/kg) per bleed
* Consumption of N8-GP (number of infusions and U/kg per month and per year)
during prophylaxis and on-demand treatment
* Haemostatic effect as measured by recovery and trough levels Factor VIII (in
all patients receiving prophylaxis treatment)
* Patient Reported Outcomes and Health Economic outcomes
* Adverse Events (AEs) and Serious Adverse Events (SAEs) reported during the
trial
* Changes in vital signs (BP, pulse, temperature, respiratory rate)
* Pharmacokinetic Outcomes
Background summary
The rationale for this trial is to investigate the safety and efficacy,
including PK and long-term safety of N8-GP when used for treatment and
prophylaxis of bleeding episodes in haemophilia A patients. One phase 1 trial
has been completed with 26 PTPs dosed with N8-GP and had undergone a safety and
PK investigation. The phase 1 trial has successfully been concluded with no
safety concerns.
Study objective
Co-Primary Objectives
* To evaluate the immunogenicity of N8-GP in previously treated patients with
haemophilia A
* To evaluate the clinical efficacy of N8-GP in bleeding prohylaxis (number of
bleeds during prophylaxis)
Secondary Objectives
* To evaluate the clinical efficacy of N8-GP when treating bleeds in patients
with haemophilia A
* To evaluate the safety of N8-GP when used for prevention of bleeds and
treatment of bleeds in patients with heamophilia A
* To evaluate PK properties of N8-GP
* To evaluate Patient Reported Outcomes (PRO)
* To evaluate the health economic impact of N8-GP treatment
* Generation of a population based PK-model for N8-GP
Study design
This phase 3 trial is a multi-centre, multi-national, open-label,
non-randomised trial evaluating safety, pharmacokinetics and clinical efficacy
of N8-GP when used for treatment of bleeding episodes and for long-term
prophylaxis.
A minimum of 155 patients must complete the Main Phase of the trial including
at least 10 patients in on-demand treatment and 145 patients in prophylaxis
treatment with N8-GP every 4 days.
A minimum of 15 of the patients in the prophylaxis arm must undergo 2 PK
sessions.
Treatment duration in the Main Phase is approximately 7-19 months. All patients
will continue in the trial until the last patient has received at least 50
exposure days of N8-GP. In this way a considerable portion of the patients will
be treated prophylactic with N8-GP for more than 1 year.
When the Main Phase of the trail has completed, all patients will be offered to
continue treatment in the Extension Phase of the trial. The extension trial is
designed to obtain long-term safety and efficacy data for prophylactic
treatment every 4 days or every 7 days, and for on-demand treatment.
Intervention
Injections with N8-GP every 4 days (prophylaxis) and/or injections with N8-GP
at the first signs of a bleeding episode (on-demand).
In the Extension Phase it is also possible to have injections with N8-GP every
7 days as prophylaxis.
Study burden and risks
It's possible that bloodwithdrawals or injections with N8-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 N8-GP.
There is a risk of development of antibodies against N8-GP and/or Factor VIII
that could decrease the effectiveness of future treatments with Factor VIII
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
- Male patients with severe congenital haemophilia A (FVIII activity <1%, according to medical records)
- Documented history of at least 150 EDs to other FVIII products
- Age * 12 years and body weight * 35 kg (except for Croatia, The Netherlands, France, Russia and Israel where the lower age limit will be 18 years)
Exclusion criteria
- Previous participation in this trial defined as withdrawal after administration N8-GP
- Any history of FVIII inhibitors
- FVIII inhibitors * 0.6 BU/mL at screening
- HIV positive, defined by medical records with CD4+ count *200/µL or a viral load of >400000 copies/mL If the data is not available in medical records within last 6 months, CD4+ will be measured at the screening visit
- Congenital or acquired coagulation disorders other than haemophilia A
- Previous significant thromboembolic events (e.g. myocardial infarction, cerebrovascular disease or deep venous thrombosis) as defined by available medical records
- Platelet count < 50,000 platelets/µL (laboratory value at the screening visit)
- ALAT > 3 times the upper limit of normal reference ranges at central laboratory
- Creatinine level * 1.5 times above upper normal limit (according to central laboratory reference ranges)
- Ongoing 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 | EUCTR2011-001142-15-NL |
| ClinicalTrials.gov | NCT01480180 |
| CCMO | NL38625.078.11 |