A Clinical Study to Evaluate the Effects of NXT007 Compared to Emicizumab Prophylaxis in People With Hemophilia A (ZEBRHA 2)

A Multicenter, Randomized, Open-Label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of NXT007 Prophylaxis Versus Emicizumab Prophylaxis in People With Hemophilia A

The purpose of this study is to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of NXT007 prophylaxis compared with emicizumab prophylaxis in people age 12 years and older with severe or moderate congenital hemophilia A without factor VIII (FVIII) inhibitors or with hemophilia A of any severity (severe, moderate, and mild) with FVIII inhibitors.

Study Overview

• Status: Recruiting
• Conditions: Hemophilia A
• Intervention / Treatment: Combination product: NXT007; Drug: Emicizumab

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: BO45887 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

Study Locations

• Japan
  • Gunma
    • Maebashi, Gunma, Japan, 371-8511
      • Recruiting
      • Gunma University Hospital
  • Nara
    • Kashihara-shi, Nara, Japan, 634-8522
      • Recruiting
      • Nara Medical University Hospital
  • Tokyo
    • Suginami-Ku, Tokyo, Japan, 167-0035
      • Recruiting
      • Ogikubo Hospital
• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • Center for Inherited Blood Disorders
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Recruiting
      • Innovative Hematology, Inc.
  • Washington
    • Seattle, Washington, United States, 98101-3932
      • Recruiting
      • Washington Center for Bleeding Disorders

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 International Unit per decilitre [IU/dL]) or moderate (FVIII:C between ≥1 IU/dL and ≤5 IU/dL) congenital hemophilia A with or without inhibitors against FVIII
• Diagnosis of mild (FVIII:C between >5 IU/dL and <40 IU/dL) congenital hemophilia A with chronic FVIII inhibitors, defined as documented FVIII inhibitor ( ≥0.6 BU/mL or ≥1.0 BU/mL only for laboratories with a historical sensitivity cutoff for inhibitor detection of 1.0 BU/mL) and chronic reduction of endogenous baseline FVIII:C to <5 IU/dL for ≥12 months
• Documented historical FVIII inhibitor assay results within the 12 months prior to enrollment
• Documentation of the details of prophylactic and episodic FVIII treatment, bypassing agent (BPA) treatment, emicizumab prophylaxis treatment, and the number and type of bleeding episodes for at least the last 6 months prior to screening
• For potential participants taking on-demand treatments prior to study entry: agreement to move to a prophylaxis treatment with either emicizumab or NXT007, according to assigned randomization

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 antiretroviral therapy to treat HIV
• Refusal to accept plasma-derived and/or blood product transfusion support in an emergency scenario
• Planned surgery (excluding minor procedures, such as non-molar tooth extraction or incision and drainage) during the study
• 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)
• 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 evidence or clinical history of prior myocardial infarction

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: Emicizumab Prophylaxis; Participants randomized to this arm will receive emicizumab prophylaxis for the main study treatment period at 3 mg/kg once weekly (QW) for 4 weeks as loading doses, followed by maintenance dosing of either 1.5 mg/kg QW, 3 mg/kg once every 2 weeks (Q2W), or 6 mg/kg once every 4 weeks (Q4W). Loading doses are not required for participants who were taking emicizumab prior to study start.	Drug: Emicizumab; Emicizumab will be administered subcutaneously (SC) using vial and syringe.; Other Names: Hemlibra; RO5534262; RG6013
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 Emicizumab 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	From Month 2 until the clinical cutoff date (at least 7 months of study treatment)

Secondary Outcome Measures

Outcome Measure	Time Frame
ABR for All Bleeds Over the Main Study Treatment Period	From Month 2 until the clinical cutoff date (at least 7 months of study treatment)
ABR for Treated Spontaneous Bleeds Over the Main Study Treatment Period	From Month 2 until the clinical cutoff date (at least 7 months of study treatment)
ABR for Treated Joint Bleeds Over the Main Study Treatment Period	From Month 2 until the clinical cutoff date (at least 7 months of study treatment)
Adjusted Mean Treatment Burden Domain Score in Comprehensive Assessment Tool of Challenges in Hemophilia (CATCH) Questionnaire - Adult Version at Month 8	Month 8
ABR for Treated Target Joint Bleeds Over the Main Study Treatment Period	From Month 2 until the clinical cutoff date (at least 7 months of study treatment)
Percentage of Participants with Zero Treated Bleeds Over the Main Study Treatment Period	From Month 2 until the clinical cutoff date (at least 7 months of study treatment)
Number of Injections and Dose per Bleed of Coagulation Factors or Bypassing Agent Administered to Treat a Bleed Over the Main Study Treatment Period	From Month 2 until the clinical cutoff date (at least 7 months of study treatment)
Annualized Injection Rate of FVIII or Bypassing Agent Over the Main Study Treatment Period	From Month 2 until the clinical cutoff date (at least 7 months of study treatment)
Annualized Consumption Rate of FVIII or Bypassing Agent Over the Main Study Treatment Period	From Month 2 until the clinical cutoff date (at least 7 months of study treatment)
Mean Treatment Burden Domain Score in CATCH Questionnaire - Adolescent Version at Month 8	Month 8
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)
Physical Impact Domain Score of the Treatment Administration Satisfaction Questionnaire (TASQ) at Specified Timepoints	At prespecified timepoints from Baseline to Month 4
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)

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 (Actual): April 27, 2026
• Primary Completion (Estimated): February 29, 2028
• Study Completion (Estimated): January 29, 2032

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 5, 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; emicizumab
• Other Study ID Numbers: BO45887; 2025-522435-33-00 (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