A Clinical Study to Evaluate the Effects of NXT007 Compared to Factor VIII Prophylaxis in Participants With Hemophilia A (ZEBRHA 1)

A Multicenter, Randomized, Open-Label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of NXT007 Prophylaxis Versus Factor VIII Prophylaxis in People With Hemophilia A Without Inhibitors

The purpose of this study is to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamics of NXT007 prophylaxis compared with Factor VIII (FVIII) prophylaxis in participants with severe or moderate congenital hemophilia A without inhibitors. The study will include people aged ≥12 years old with severe or moderate congenital hemophilia A without inhibitors on previous FVIII prophylaxis treatment.

Study Overview

• Status: Recruiting
• Conditions: Hemophilia A
• Intervention / Treatment: Combination product: NXT007; Drug: Human Coagulation Factor VIII

• Study Type: Interventional
• Enrollment (Estimated): 126
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: WO45886 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

Study Locations

• Japan
  • Nara
    • Kashihara-shi, Nara, Japan, 634-8522
      • Recruiting
      • Nara Medical University Hospital
  • Tokyo
    • Shinjuku-Ku, Tokyo, Japan, 160-0023
      • Recruiting
      • Tokyo Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of severe (FVIII:C <1 IU/dL [International Unit per decilitre]) or moderate (FVIII:C between ≥1 IU/dL and ≤5 IU/dL) congenital hemophilia A without inhibitors against FVIII
• No documented inhibitor (i.e., <0.6 BU/mL [Bethesda unit per millilitre]), FVIII half-life ≥6 hours, or FVIII recovery >66% in the last 3 years prior to screening
• Documented historical negative test for FVIII inhibitor (i.e., <0.6 BU/mL) within 12 months prior to enrollment
• Documentation of the details of prophylactic and episodic FVIII treatment and of the number and type of bleeding episodes for at least the last 6 months prior to screening
• Agreement to adhere to the contraception requirements (for potential participants with childbearing potential)

Exclusion Criteria:

• Sensitivity to any of the study investigations, or components thereof, or drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study
• Use of systemic immunomodulators (e.g., interferon or rituximab) at the time of enrollment or planned use during the study, except for anti-retroviral therapy to treat HIV
• Planned surgery (excluding minor procedures such as non-molar tooth extraction, incision and drainage) during the study
• History or presence of an abnormal ECG that is deemed clinically significant, (e.g., complete left bundle branch block, second- or third- degree atrioventricular heart block) or ECG evidence or clinical history of prior myocardial infarction
• Refusal to accept plasma-derived and/or blood product transfusion support in an emergency scenario
• History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Main Study Treatment Period: NXT007 Prophylaxis; Participants randomized to this arm will receive NXT007 prophylaxis for the main study treatment period.	Combination product: NXT007; NXT007 will be administered subcutaneously (SC) using an integrated drug-device combination product.; Other Names: RO7589655; RG6512; Zemocimig
Active Comparator: Main Study Treatment Period: FVIII SOC Prophylaxis; Participants randomized to this arm will receive FVIII standard of care (SOC) prophylaxis for the main study treatment period.	Drug: Human Coagulation Factor VIII; Factor VIII (FVIII) prophylaxis standard of care (SOC) will be administered at the dose and frequency as stated in the local labels and per local country practice.
Experimental: Open-Label Extension Period: NXT007 Prophylaxis; After the main study treatment period, participants in the NXT007 arm will be able to continue with NXT007 dosing, and participants in the FVIII arm will be able to switch to NXT007, in the open-label extension period.	Combination product: NXT007; NXT007 will be administered subcutaneously (SC) using an integrated drug-device combination product.; Other Names: RO7589655; RG6512; Zemocimig

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Annualized Bleed Rate (ABR) for Treated Bleeds Over the Main Study Treatment Period	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Preoccupation Domain Score of the CATCH Questionnaire (Adult and Adolescent Versions)	At prespecified timepoints from Baseline until Study Completion (approximately 3.5 years)
Change From Baseline in Social Activity Impact Domain Score of the CATCH Questionnaire (Adult and Adolescent Versions)	At prespecified timepoints from Baseline until Study Completion (approximately 3.5 years)
Change From Baseline in Recreational Activity Impact Domain Score of the CATCH Questionnaire (Adult and Adolescent Versions)	At prespecified timepoints from Baseline until Study Completion (approximately 3.5 years)
Incidence and Severity of Adverse Events, With Severity Determined According To National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE V5.0) Grading Scale	From Baseline until Study Completion (approximately 3.5 years)
Incidence and Severity of Thromboembolic Events and Thrombotic Microangiopathy	From Baseline until Study Completion (approximately 3.5 years)
Incidence and Severity of Injection-Site Reactions	From Baseline until Study Completion (approximately 3.5 years)
Incidence of Adverse Events Leading to Discontinuation of Assigned Study Treatment	From Baseline until Study Completion (approximately 3.5 years)
Incidence of Severe Hypersensitivity, Anaphylaxis, or Anaphylactoid Reactions	From Baseline until Study Completion (approximately 3.5 years)
Plasma Concentration of NXT007	At prespecified timepoints from Baseline to Study Completion (approximately 3.5 years)
Percentage of Participants With Anti-Drug Antibodies (ADAs) Against NXT007 at Baseline and During the Study	At prespecified timepoints from Baseline to Study Completion (approximately 3.5 years)
Percentage of Participants With Neutralizing ADAs Against NXT007	At prespecified timepoints from Baseline to Study Completion (approximately 3.5 years)
ABR for All Bleeds Over the Main Study Treatment Period	6 months
ABR for Treated Spontaneous Bleeds Over the Main Study Treatment Period	6 months
ABR for Treated Joint Bleeds Over the Main Study Treatment Period	6 months
Adjusted Mean Treatment Burden Domain Score in Comprehensive Assessment Tool of Challenges in Hemophilia (CATCH) Questionnaire - Adult Version at Month 7	Month 7
ABR for Treated Target Joint Bleeds Over the Main Study Treatment Period	6 months
Percentage of Participants with Zero Treated Bleeds Over the Main Study Treatment Period	6 months
Number of Injections and Dose per Bleed of Coagulation Factors Administered to Treat a Bleed Over the Main Study Treatment Period	6 months
Annualized FVIII Injection Rate Over the Main Study Treatment Period	6 months
Annualized FVIII Consumption Rate Over the Main Study Treatment Period	6 months
Mean Treatment Burden Domain Score in CATCH Questionnaire - Adolescent Version at Month 7	Month 7
Physical Impact Domain Score of the Treatment Administration Satisfaction Questionnaire (TASQ) at Specified Timepoints	At prespecified timepoints from Baseline to Month 10

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Collaborators: Chugai Pharmaceutical
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Estimated): May 9, 2026
• Primary Completion (Estimated): September 23, 2027
• Study Completion (Estimated): September 23, 2031

Study Registration Dates

• First Submitted: February 11, 2026
• First Submitted That Met QC Criteria: February 11, 2026
• First Posted (Actual): February 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hemophilia A; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Blood Proteins; Blood Coagulation Factors; Protein Precursors; Factor VIII
• Other Study ID Numbers: WO45886; 2025-522434-32-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No