Posology : מינונים

4.2    Posology and method of administration

Treatment should be administered in a centre which is specialised in stereotactic neurosurgery, by a qualified neurosurgeon under controlled aseptic conditions.

Posology

Patients will receive a total dose of 1.8 × 1011 vg delivered as four 0.08 mL (0.45 × 1011 vg) infusions (two per putamen).
Upstaza-SPC-0424-V1
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The posology is the same for the entire population covered by the indication.

Special populations

Paediatric population
The safety and efficacy of eladocagene exuparvovec in children aged below 18 months have not yet been established. No data are available.
There is limited experience in patients aged 12 years and older. The safety and efficacy of eladocagene exuparvovec in these patients have not been established. Currently available data are described in section 5.1. No dose adjustment should be considered.

Hepatic and renal impairment
The safety and efficacy of eladocagene exuparvovec in patients with hepatic and renal impairment have not been evaluated.

Immunogenicity
There is no safety or efficacy data for patients whose pre-treatment neutralising antibody levels to AAV2 was > 1:20 (see section 4.4).

Method of administration

Intraputaminal use.
Preparation
Upstaza is a sterile solution for infusion that requires thawing and preparation by the hospital pharmacy prior to administration.

For detailed instructions on preparation, administration, measures to take in case of accidental exposure and disposal of Upstaza, see section 6.6.

Neurosurgical administration
Upstaza is a single use vial administered by bilateral intraputaminal infusion in one surgical session at two sites per putamen. Four separate infusions of equal volumes are performed to the right anterior putamen, right posterior putamen, left anterior putamen, and left posterior putamen.
For instructions on preparation of the surgical suite infusion of Upstaza, see section 6.6.

The target infusion sites are defined per standard stereotactic neurosurgical practice. Upstaza is administered as a bilateral infusion (2 infusions per putamen) with an intracranial cannula. The final 4 targets for each trajectory should be defined as 2 mm dorsal to (above) the anterior and posterior target points in the mid-horizonal plane (Figure 1).



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Figure 1         Four target points for infusion sites



•     After stereotactic registration is complete, the entry point on the skull should be marked.
Surgical access through the skull bone and dura should be performed.

•     The infusion cannula is placed at the designation point in the putamen using stereotactic tools based on the trajectories planned. Of note, the infusion cannula is placed and infusion performed separately for each putamen.

•     Upstaza is infused at a rate of 0.003 mL/min at each of the 2 target points in each putamen; 0.08 mL of Upstaza is infused per putaminal site resulting in 4 infusions with a total volume of 0.320 mL (or 1.8 × 1011 vg).

•     Starting with the first target site, the cannula is inserted through a burr hole into the putamen and then slowly withdrawn, distributing the 0.08 mL of Upstaza across the planned trajectory to optimise distribution across the putamen.

•     After the first infusion, the cannula is withdrawn and then re-inserted at the next target point, repeating the same procedure for the other 3 target points (anterior and posterior of each putamen).

•     After standard neurosurgical closure procedures, the patient then undergoes a postoperative computerised tomography imaging examination to ensure there are no complications (ie, bleeding).

•     The patient must reside within the vicinity of the hospital where the procedure was performed for a minimum of 48 hours following the procedure. The patient may return home, post-procedure, based on treating physician’s advice. The post-treatment care should be managed by neurosurgeon and the referring neurologist. The patient should have a follow-up 7 days after surgery to ensure that no complications have developed. A second follow-up visit should take place 2 weeks later (ie, 3 weeks after the surgery) to monitor post-surgical recovery and occurrence of adverse events.