ROCTAVIAN Solution for infusion Ref.[50172] Active ingredients: Valoctocogene roxaparvovec

Treatment should be initiated under the supervision of a physician experienced in the treatment of haemophilia and/or bleeding disorders. This medicinal product should be administered in a setting where personnel and equipment are immediately available to treat infusion-related reactions (see sections 4.4 and 4.8).

ROCTAVIAN should only be administered to patients who have demonstrated absence of anti-AAV5 antibodies by a validated assay.

Posology

The recommended dose of ROCTAVIAN is 6 × 10¹³ vector genomes per kilogram (vg/kg) body weight, administered as a single intravenous infusion.

Calculating the patient’s dose in millilitres (mL) and number of vials required

Calculation of patient’s dose volume in mL:

Body weight in kg multiplied by 3 = dose in mL

The multiplication factor 3 represents the per kilogram dose (6 × 10¹³ vg/kg) divided by the amount of vector genomes per mL of the ROCTAVIAN solution (2 × 10¹³ vg/mL).

Calculation of number of vials to be thawed:

Patient’s dose volume (mL) divided by 8 = number of vials to be thawed (round up to next whole number of vials).

The division factor 8 represents the minimum volume of ROCTAVIAN extractable from a vial (8 mL).

Table 1. Example of dose volume and number of vials to be thawed:

Discontinuation of factor VIII concentrates/haemostatic agents

When discontinuing factor VIII concentrates/haemostatic agents, physicians should consider the following:

• Patient’s factor VIII activity levels are sufficient to prevent spontaneous bleeding episodes.
• The duration of effect of factor VIII concentrates/haemostatic agents.

Special populations

Hepatic impairment

The safety and efficacy of valoctocogene roxaparvovec in patients with hepatic disorders have not been established. Valoctocogene roxaparvovec is contraindicated in patients with acute or uncontrolled chronic hepatic infections, or in patients with known significant hepatic fibrosis, or cirrhosis (see section 4.3). This medicinal product is not recommended for use in patients with other hepatic disorders (see section 4.4).

Renal impairment

No dose adjustments are recommended in patients with renal impairment.

Elderly

No dose adjustments are recommended in elderly patients. Limited data are available in patients aged 65 years and older.

Paediatric population

The safety and efficacy of ROCTAVIAN in children and adolescents less than 18 years of age have not yet been established. No data are available.

Method of administration

ROCTAVIAN must be administered via intravenous infusion. Do not infuse as an intravenous push or bolus.

Administer this medicinal product in a setting where personnel and equipment are immediately available to treat infusion-related reactions (see sections 4.4 and 4.8).

ROCTAVIAN administration can begin at an infusion rate of 1 mL/min, which can be increased every 30 minutes by 1 mL/min to up to a maximum rate of 4 mL/min. The infusion rate may be slowed or interrupted if the patient develops an infusion related reaction (see section 4.4).

For detailed instructions on the preparation, administration, and disposal of the medicinal product, see section 6.6.

There is no experience with accidental infusion of too high a dose volume. If considered necessary, treatment of an overdose should be symptomatic and supportive. Receiving higher doses than recommended may result in higher factor VIII activity levels and may theoretically be associated with increased risk of thrombotic events.

4 years.

Once thawed: chemical and physical in-use stability after thawing has been demonstrated for 10 hours at 25°C, including hold time in intact vial, preparation time into the syringes, and time for infusion (see section 6.6).

If necessary, an intact vial (stopper not yet punctured) that has been thawed can be stored refrigerated (2°C to 8°C) for up to 3 days, upright and protected from light (e.g., in the original carton).

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user (see section 6.6).

Store and transport frozen at ≤ -60°C. ROCTAVIAN must remain frozen until the patient is ready for treatment to ensure viable product is available for patient administration. Once thawed, do not refreeze.

Store in the original carton in order to protect from light. Store upright.

For storage conditions after thawing of the medicinal product, see section 6.3.

10 mL vial (cyclic olefin polymer plastic resin) with a stopper (chlorobutyl rubber with fluoropolymer coating), crimp seal (aluminium) and flip-off cap (polypropylene) containing 8 mL of solution for infusion.

Each carton contains 1 vial.

Precautions to be taken before handling or administering the medicinal product

Each vial is for single use only.

This medicine contains genetically modified organisms (GMOs).

During preparation, administration, and disposal, personal protective equipment (including gown, safety glasses, mask, and gloves) should be worn when handling the valoctocogene roxaparvovec solution and materials that have been in contact with the solution (solid and liquid waste).

ROCTAVIAN must not be exposed to the light of an ultraviolet radiation disinfection lamp.

ROCTAVIAN must be prepared using aseptic technique.

When assembling the infusion system, it must be ensured that the components' surface in contact with the ROCTAVIAN solution consist of the compatible materials listed in Table 10.

Table 10. Compatible infusion system component materials:

^a Tubing extensions should not exceed approximately 100 cm in length.

ROCTAVIAN should be infused using a flow rate-controlled syringe pump.

The following syringes must be prepared:

• Syringes containing ROCTAVIAN (the number of syringes will depend on the patient’s dose volume).
• One syringe containing sodium chloride 9 mg/mL (0.9%) solution for injection for infusion line flushing after completion of the ROCTAVIAN infusion.

Infusion requires high-volume, in-line, low protein binding infusion filters with a pore size of 0.22 microns and a maximum operating pressure adequate for the syringe pump or pump settings. Availability of a sufficient number of replacement filters must be ensured, according to the filters' specification for maximum filtered fluid volume.

Thawing and inspection

• ROCTAVIAN must be thawed at room temperature. Do not thaw or warm vials any other way. Thawing time is approximately 2 hours.
• Keep each vial in its carton until ready to thaw. ROCTAVIAN is sensitive to light.
• Remove the required number of vials from their cartons.
• Inspect the vials for damage to the vial or cap. Do not use if damaged.
• Set the vials upright. To achieve optimal thawing, spread them out evenly or place them in racks that have been kept at room temperature.
• Visually confirm that all vials have been thawed. There should be no visible ice. Very gently invert each vial 5 times to mix. It is important to minimise foaming. Let the solution settle for approximately 5 minutes before continuing.
• Then visually inspect the fully thawed vials. Do not use a vial if the solution is not clear, not colourless to pale yellow, or contains visible particles.

For microbiological safety, keep the thawed solution in the vials until it has to be extracted into syringes for infusion.

Time window for further preparation and administration

After thawing, infusion of the solution should be completed within the 10-hour in-use stability limit at 25°C (see section 6.3). The infusion time depends on infusion volume, rate and patient response and can be, for example, 2 to 5 hours or longer for a patient weighing 100 kg.

Extraction into syringes

Using 18 to 21-gauge sharp needles, slowly extract the entire calculated dose volume of ROCTAVIAN from the vials into the syringes.

Adding the in-line filter and priming the infusion system

• Insert the in-line filter close to the infusion site.
• Prime tubing and filter with ROCTAVIAN.
• When replacing filters during the infusion, use sodium chloride 9 mg/mL (0.9%) solution for injection for priming and flushing.

Administration

• Do not administer this medicinal product before the solution has reached room temperature.
• Infuse the solution through a suitable peripheral vein, using an infusion catheter and a programmable syringe pump.
• Start the infusion at a rate of 1 mL/min. If tolerated, the rate may be increased every 30 minutes by 1 mL/min up to a maximum rate of 4 mL/min (see section 4.2). If clinically indicated for an infusion-related reaction, decrease the rate or stop the infusion and, as necessary, administer additional medicinal products such as systemic antihistamines, corticosteroids and/or intravenous fluids to manage the infusion reaction or prior to restarting the infusion. When restarting the infusion, start at a rate of 1 mL/min and consider maintaining it at a previously tolerated level for the remainder of the infusion.
• To ensure the patient receives the complete dose, after the volume of the last syringe containing ROCTAVIAN is infused, infuse a sufficient volume of sodium chloride 9 mg/mL (0.9%) solution for injection through the same tubing and filter and at the same infusion rate.
• Maintain venous access during the subsequent observation period (see section 4.4).

Measures to take in case of accidental exposure

All spills of valoctocogene roxaparvovec must be wiped with absorbent gauze pad and the spill area must be disinfected using a bleach solution followed by alcohol wipes.

Precautions to be taken for the disposal of the medicinal product

Unused medicinal product and waste that have been in contact with ROCTAVIAN (solid and liquid waste) must be disposed of in compliance with the local guidance for pharmaceutical waste.