Phase 3 Multicenter Randomized Open‑Label Trial of Efanesoctocog Alfa Intensified Replacement Therapy for Synovitis in Patients with Congenital Hemophilia A

The primary objective is to evaluate the efficacy of intensified replacement therapy with efanesoctocog alfa in reducing or resolving signs of synovitis in patients with congenital hemophilia A. This addresses joint inflammation that contributes to morbidity. Secondary objectives are: • Characterization of the pharmacokinetic profile of the regimen; • Assessment of efficacy in preventing bleeding episodes; • Evaluation of safety parameters associated with the intensified therapy.

The trial enrolled male participants aged 18 to 70 years who have severe to moderate congenital hemophilia A and documented synovitis of the elbow, knee, or ankle (ultrasound score ≥ 1). All subjects were required to be on a stable prophylactic regimen with licensed FVIII products for at least six months prior to screening. Eligibility required the ability to provide informed consent and to comply with study procedures. The sponsor did not provide the total number of participants enrolled.

The study is a multicenter, randomized, open‑label, phase III trial evaluating intensified replacement therapy with efanesoctocog alfa in adult males with Congenital hemophilia A who exhibit synovitis of the elbow, knee, or ankle. Participants are screened during a eligibility visit that includes informed‑consent verification, medical history, and blinded ultrasound assessment of synovial hypertrophy (HEAD‑US). Eligible subjects are then randomized to receive weight‑based intravenous doses of 35 IU/kg of the investigational product administered according to the prescribed prophylactic schedule for a treatment period of 12 months. Follow‑up visits occur at regular intervals (e.g., monthly for safety labs, quarterly for pharmacokinetic sampling, and bi‑annual ultrasound evaluations) to monitor FVIII trough levels, bleeding rates, and joint status. The final end‑of‑study visit at month 12 includes a comprehensive ultrasound assessment, collection of adverse‑event data, and determination of treatment response. Overall participant involvement spans approximately 13 months, including the screening phase. Early termination may occur if a participant experiences a serious treatment‑emergent adverse event, withdraws consent, fails to adhere to the protocol, or if the investigator deems continuation clinically inappropriate. The trial recruitment period is planned from July 2026 to May 2029.

ALTUVOCT 250 IU powder and solvent for solution for injection is supplied as a sterile lyophilized powder that is reconstituted with the provided solvent to a solution for injection. The product contains the recombinant coagulation factor efanesoctocog alfa and is administered by intravenous injection at a weight‑based dose of 35 IU/kg per infusion; the dosing interval is defined by the study protocol.

ALTUVOCT 500 IU powder and solvent for solution for injection is provided in the same pharmaceutical form and is reconstituted to a solution for injection. It delivers efanesoctocog alfa intravenously at a dose of 35 IU/kg per infusion according to the protocol‑specified schedule.

ALTUVOCT 1 000 IU powder and solvent for solution for injection is prepared as a solution for injection and contains efanesoctocog alfa. The investigational product is given by intravenous injection at 35 IU/kg per infusion, with the frequency determined by the trial regimen.

ALTUVOCT 2 000 IU powder and solvent for solution for injection is a lyophilized powder reconstituted to a solution for injection. It provides efanesoctocog alfa administered intravenously at 35 IU/kg per infusion, following the dosing schedule outlined in the protocol.

ALTUVOCT 3 000 IU powder and solvent for solution for injection is supplied as a powder for reconstitution to a solution for injection. The active substance, efanesoctocog alfa, is delivered by intravenous injection at a dose of 35 IU/kg per infusion, with administration frequency defined by the study protocol.

No placebo, comparator, or additional investigational agent is used in this study; participants receive only the assigned dose of efanesoctocog alfa. Standard‑of‑care management of hemophilia A may be continued as required, and rescue therapy is permitted per protocol specifications.

Compliance with the dosing regimen is monitored through documented infusion logs, verification of reconstitution procedures, and periodic measurement of plasma factor VIII activity levels to confirm appropriate exposure.

Efficacy will be evaluated using a primary endpoint defined as the proportion of patients achieving treatment response (TR) after 12 months. TR is defined as a reduction or resolution of synovial hypertrophy in at least one affected joint according to the synovial hypertrophy domain of the Hemophilia Early Arthropathy Detection with Ultrasound (HEAD‑US) score performed by a blinded ultrasound expert team.

Secondary efficacy assessments include pharmacokinetic and bleed‑prevention parameters: FVIII trough level, time spent with FVIII activity > 30 IU/dL, time spent with FVIII activity > 50 IU/dL, Annualized bleeding rate (ABR) for all treated bleeds, and Annualized joint bleeding rate (AjBR) for treated joint bleeds. Additional secondary measures address synovitis resolution, specifically the proportion of joints with TR and the proportion of patients with complete resolution of synovitis in all joints. Safety will be monitored through treatment‑emergent adverse events (TEAE).

Efficacy data will be collected using standardized ultrasound imaging reviewed by the blinded expert team, quantitative laboratory assays for factor VIII activity, and patient‑reported bleed logs. The primary endpoint will be assessed at the 12‑month visit, while secondary endpoints will be evaluated at scheduled study visits throughout the treatment period as specified in the protocol.