Phase III Randomized Open‑Label Trial of Subcutaneous NXT007 Prophylaxis versus Intravenous Factor VIII Prophylaxis in Patients with Hemophilia A without Inhibitors

The primary objective is to assess the efficacy of NXT007 prophylaxis compared with factor VIII prophylaxis by demonstrating superiority for the primary endpoint of treated bleeds, a clinically relevant measure of bleeding control in individuals with hemophilia A without inhibitors. Secondary objectives include:

• Evaluation of efficacy based on predefined secondary endpoints.
• Assessment of quality of life using a health‑related quality of life questionnaire.
• Measurement of treatment administration satisfaction via the Treatment Administration Satisfaction Questionnaire (TASQ).
• Evaluation of safety parameters.
• Characterization of the pharmacokinetics of NXT007.
• Assessment of the immunogenicity of NXT007.

The trial enrolled 84 individuals diagnosed with Hemophilia A Without Inhibitors, including both male and female participants spanning pediatric to adult age groups as indicated by the study’s age‑range codes. All subjects exhibited severe (FVIII:C < 1 IU/dL) or moderate (FVIII:C ≥ 1 IU/dL and ≤ 5 IU/dL) congenital hemophilia A, with documented absence of FVIII inhibitors (< 0.6 BU/mL) and a documented FVIII half‑life of at least 6 hours. Eligibility required a negative inhibitor test within the preceding 12 months and comprehensive records of prophylactic and episodic FVIII treatment for the six months before screening. Participants were required to comply with contraception guidelines if of childbearing potential, and the cohort included individuals classified as vulnerable. The study population was selected based on these diagnostic and laboratory criteria to ensure appropriate representation for the evaluation of NXT007 prophylaxis versus standard FVIII prophylaxis.

The study is a multicenter, randomized, open‑label, Phase III trial evaluating the efficacy, safety, pharmacokinetics and pharmacodynamics of subcutaneous NXT007 prophylaxis versus intravenous factor VIII prophylaxis in individuals with Hemophilia A without inhibitors. After an initial screening visit to confirm eligibility criteria, participants are randomized to receive either NXT007 or factor VIII and commence a 6‑month treatment period. Study visits occur at baseline (Day 0), monthly for safety assessments, pharmacokinetic sampling, and documentation of bleed events, with a specific quality‑of‑life evaluation at the Month 7 visit, followed by an end‑of‑study visit after the 6‑month period. The overall participant involvement therefore spans approximately 7 months, including screening and follow‑up. Early termination may occur if a participant develops a confirmed inhibitor, experiences a serious adverse event related to study drug, or withdraws consent. Primary efficacy is measured by the annualized number of treated bleeds (ABR) during the main treatment period, with multiple secondary endpoints assessing bleed rates, injection burden, quality of life, and safety outcomes.

The investigational product, NXT007, is a humanised IgG4 monoclonal antibody directed against activated factor IX (FIXa) and factor X (FX). It is supplied as a sterile solution for injection and is administered by subcutaneous injection. The dosing regimen follows a prophylactic schedule defined in the protocol, with each dose delivered at the prescribed interval. The volume and concentration of each injection are determined by the participant’s body weight and the target trough level, and the preparation is not pre‑filled; it is drawn from a vial immediately before administration.

The comparator treatment consists of coagulation factor VIII (simoctocog alfa). It is provided in the pharmaceutical form identified as PHF00231MIG and is administered by intravenous infusion. Dosing is individualized according to the participant’s weight and bleeding phenotype, with prophylactic infusions given at regular intervals as per standard‑of‑care guidelines for patients with Hemophilia A. The factor VIII product is supplied in a vial for reconstitution prior to infusion.

All study medications are recorded in the participant’s case report form. Administration times are logged, and compliance is assessed by review of infusion logs and drug accountability records. Participants receive training on injection technique for subcutaneous administration and on aseptic preparation for intravenous infusions. Compliance monitoring includes scheduled visits for drug accountability, assessment of adherence to the dosing schedule, and documentation of any missed or delayed doses.

The efficacy assessment focuses on the frequency of bleeding events and health‑related quality of life during the main 6‑month treatment period. The primary efficacy parameter is the annualized number of treated bleeds (ABR), calculated from prospectively recorded bleed logs. Secondary efficacy parameters include the ABR for all bleeds (treated and untreated), treated spontaneous bleeds, treated joint bleeds, treated target‑joint bleeds, and the proportion of participants with zero treated bleeds. Additional secondary measures comprise quality‑of‑life domain scores from adult and adolescent questionnaires administered at the Month 7 visit, changes from baseline in pre‑occupation, social activity impact, recreational activity impact, and physical‑impact domain scores at specified timepoints, as well as the number of injections and dose per bleed, and the annualized factor VIII injection rate and consumption.

Bleeding events are captured using patient‑reported outcome diaries, with each event classified by type (spontaneous, joint, target joint) and treatment status. Quality‑of‑life assessments employ validated disease‑specific instruments administered at baseline and at the Month 7 visit. Plasma concentrations of NXT007 and the presence of anti‑drug antibodies are measured by laboratory assays at predefined visits. Efficacy data are analyzed by calculating annualized rates over the 6‑month period and by comparing the NXT007 prophylaxis arm with the factor VIII prophylaxis arm using superiority testing for the primary ABR endpoint, with secondary endpoints evaluated descriptively and inferentially as appropriate.