NN7999-3774 Safety, Efficacy and Pharmacokinetics of N9-GP in Previously Treated Children with Hemophilia B
This study is an open label, single-arm, multinational non-controlled trial investigating safety, efficacy and PK of n9-GP in prophylaxis and treatment of breakthrough bleeding episodes in pediatric male patients with hemophilia B.
The trial consists of a main phase and an extension phase. The duration of the main phase for each patient will be minimum 52 weeks. after completion of the main phase, patients can continue in an extension phase, lasting until n9-GP is commercially available in the relevant countries or if the n9-GP program is terminated, unless otherwise required by national regulations.
The patients will be divided into two age groups; 0-6 years and 7-12 years. a minimum of 10 patients in each age group must complete the main phase of the trial with at least 50 exposure days (eD). The trial has one treatment arm where all patients receive n9-GP once weekly for prophylaxis. in the extension phase, the investigators are allowed to individualize both dose levels and/or dosing frequency. in addition, n9-GP will be administered in case of breakthrough bleeding episodes during the main phase and extension phase.
The trial will provide information on safety, efficacy and PK of n9-GP in pediatric
previously treated patients with hemophilia B, aged [LessThanorequalTo]12 years and a FiX activity level of 2%.
The purpose of the present trial is to provide sufficient exposure to n9-GP to evaluate
immunogenicity of n9-GP and to provide efficacy data for n9-GP in long-term prophylaxis.
The main phase of the trial will generate safety data from at least 50 eDs on each patient collected during minimum 52 weeks continuous treatment with measurable FiX activity levels. one eD is defined as each day a patient is administered FiX for prophylaxis, prevention, and/or on-demand treatment.
The trial is not controlled by a placebo group. There will be no randomization; this is a single-arm trial. Patients will be stratified into two inclusive age groups at the time of signed informed consent; 0-6 years and 7-12 years. Patients belonging to the youngest age group will not be included in the trial before PK data from Visit 2 for 5 patients in the 7-12 year age group are evaluated.
The rationale for choosing a multinational design is to ensure a sufficient screening pool of patients with this rare disorder, to meet local regulatory requirements and to reflect the future patient population.
around 40 patients will be screened in order to start approximately 24 patients on trial product out of which 10 patients in each of the two age groups must complete the main phase of the trial. The duration of treatment in the main phase is minimum 52 weeks and at least 50 eDs. The duration of treatment in the extension phase is until n9-GP is commercially available the n9-GP program is terminated, unless otherwise required by national regulations.
The dose for treatment of a mild or moderate bleeding episode, for example a joint bleed, is a single dose of 40 u/kg since this dose is expected to give a recovery of at least 60-70% FiX activity and the FiX activity level 5 days after dosing is still expected to be above 20%. if there is no apparent effect of 40 u/kg, the patient or parent(s)/legally acceptable representative (LaR) should contact the investigator prior to administration of the second dose of 40 u/kg. a severe bleed should be treated immediately at home or at a local emergency room with 80 u/kg and the trial site must be contacted immediately thereafter for further instructions or transport to the trial site.
Minor surgeries and placement of central venous access ports can be performed while participating
in this trial by administering an additional dose of 40 u/kg n9-GP. Patients in need of major surgery will be withdrawn from the trial.
1.Informed consent obtained before any trial-related activities. (Trial-related activities are any
procedure that would not have been performed during normal management of the patient)
2. Male patients with moderately severe or severe congenital haemophilia B with a FIX activity
level <=2% according to medical records
3. Age <=12 years (until patient turns 13 years, at time of inclusion)
4. Body weight >=10 kg
5. History of at least 50 EDs to other FIX products
6. The patient and/or parent(s)/caregiver are capable of assessing a bleeding episode, keeping an
eDiary, capable of conducting home treatment and otherwise able to follow trial procedures