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 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 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 dose for treatment of a mild or moderate bleeding episode 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, or aligned with local practice after confirmation of the sponsor's medical expert. Minor surgery is defined as an invasive operative procedure where only the skin, the mucous membranes or superficial connective tissue, skin excisions, drainage of abscess or simple dental procedures.
Major surgery may be performed during participation in the current trial. in a separate completed n9-GP surgery trial (paradigm 3) 13 adults and adolescent patients underwent major surgery where the hemostatic effect in all study participatnts was reported as either good or excellent and the drug appeared to have a safe and well tolerated profile. Major sugery in the current trial should be planned and conducted in accordance with the recommendations in the World Federation of Hemophilia Guidelines for the management of hemophilia.
Major surgery may be performed using general anaesthesia, spinal anaesthesia, epidural anaesthesia, conscious sedation, local anaesthesia or with a combination of these modalities.
Major surgery is defined as any invasive operative procedure that require several days of
substitution therapy and/or where any one or more of the following occur:
1.* a body cavity is entered
2. a mesenchymal barrier (eg pleura, peritoneum or dura) is crossed
3.* a fascial plane is opened
4.* an organ is removed
5.* When a normal anatomy is operatively altered
6.* Major elective orthopaedic surgery
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