Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202607757570833 Date of Registration: 31/07/2026
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A clinical study to evaluate the effects of NXT007 compared to factor VIII prophylaxis in people with Hemophilia A
Official scientific title 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
Brief summary describing the background and objectives of the trial 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. Primary Objective: To evaluate the efficacy of NXT007 prophylaxis compared with FVIII prophylaxis based on the superiority assessment of the primary endpoint Secondary Objectives: To evaluate the efficacy of NXT007 prophylaxis compared with FVIII prophylaxis To evaluate the quality of life of participants treated with NXT007 prophylaxis compared with FVIII prophylaxis based on health-related quality of life To evaluate participants’ satisfaction with SC and IV treatment administration To evaluate the safety of NXT007 prophylaxis compared with FVIII prophylaxis To characterize the pharmacokinetics of NXT007 To evaluate the immunogenicity of NXT007
Type of trial RCT
Acronym (If the trial has an acronym then please provide) ZEBRHA 1
Disease(s) or condition(s) being studied Haematological Disorders
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 31/07/2026
Actual trial start date
Anticipated date of last follow up 24/08/2031
Actual Last follow-up date
Anticipated target sample size (number of participants) 2
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
DOH-27-072026-9047 SANCTR
WO45886 Sponsor issued
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Allocation Sequence/Code was not concealed Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group NXT007 NXT007 (test product) group: Participants will receive loading doses on Day 1 and Day 15 of Month 1 and thereafter will receive monthly SC maintenance doses according to body weight. After the main study treatment period, which will be 6 months, participants randomized to NXT007 will be able to continue with NXT007 dosing in the open-label extension phase (OLE; approximately 3 years). The total duration of study participation for an individual is expected to be approximately 3.5 years (6 months in the main treatment period, and at least 3 years in the OLE), or longer depending on duration of recruitment for the study NXT007 (RO7589655) administered subcutaneously via an autoinjector 1
Control Group FVIII prophylaxis Dose and frequency as per local prescribing information. The usual doses are 20 to 40 IU of human plasma derived FVIII per kg body weight at intervals of 2 to 3 days. The total duration of study participation for a participant is expected to be approximately 3.5 years (6 months in the main treatment period, and at least 3 years in the OLE), or longer depending on the duration of recruitment for the study. Active comparator 1 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
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) 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) 80 and over: 80+ Year,Adolescent: 13 Year(s)-17 Year(s),Adult: 18 Year(s)-44 Year(s),Aged: 65 Year(s)-79 Year(s),Middle Aged: 45 Year(s)-64 Year(s) 12 Year(s) 105 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 21/04/2026 University of the Witwatersrand Human Research Ethics Committee Medical
Ethics Committee Address
Street address City Postal code Country
31 Princess of Wales Terrace, Parktown Johannesburg 2193 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 03/07/2026 SAHPRA
Ethics Committee Address
Street address City Postal code Country
402 Kirkness Street Pretoria 0083 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Annualized Bleed Rate (ABR) for Treated Bleeds Over the Main Study Treatment Period 6 months
Secondary Outcome ABR for All Bleeds Over the Main Study Treatment Period 6 months
Secondary Outcome ABR for Treated Spontaneous Bleeds Over the Main Study Treatment Period 6 months
Secondary Outcome ABR for Treated Joint Bleeds Over the Main Study Treatment Period 6 months
Secondary Outcome Adjusted Mean Treatment Burden Domain Score in Comprehensive Assessment Tool of Challenges in Hemophilia (CATCH) Questionnaire - Adult Version at Month 7 Month 7
Secondary Outcome ABR for Treated Target Joint Bleeds Over the Main Study Treatment Period 6 months
Secondary Outcome Percentage of Participants with Zero Treated Bleeds Over the Main Study Treatment Period 6 months
Secondary Outcome Number of Injections and Dose per Bleed of Coagulation Factors Administered to Treat a Bleed Over the Main Study Treatment Period 6 months
Secondary Outcome Annualized FVIII Injection Rate Over the Main Study Treatment Period 6 months
Secondary Outcome Annualized FVIII Consumption Rate Over the Main Study Treatment Period 6 months
Secondary Outcome Mean Treatment Burden Domain Score in CATCH Questionnaire - Adolescent Version at Month 7 Month 7
Secondary Outcome 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
Secondary Outcome 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
Secondary Outcome 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
Secondary Outcome Physical Impact Domain Score of the Treatment Administration Satisfaction Questionnaire (TASQ) at Specified Timepoints At prespecified timepoints from Baseline to Month 10
Secondary Outcome 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
Secondary Outcome Incidence and Severity of Thromboembolic Events and Thrombotic Microangiopathy From Baseline until Study Completion approximately 3.5 years
Secondary Outcome Incidence and Severity of Injection-Site Reactions From Baseline until Study Completion approximately 3.5 years
Secondary Outcome Incidence of Adverse Events Leading to Discontinuation of Assigned Study Treatment From Baseline until Study Completion approximately 3.5 years
Secondary Outcome Incidence of Severe Hypersensitivity, Anaphylaxis, or Anaphylactoid Reactions From Baseline until Study Completion approximately 3.5 years
Secondary Outcome Plasma Concentration of NXT007 At prespecified timepoints from Baseline to Study Completion approximately 3.5 years
Secondary Outcome 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
Secondary Outcome Percentage of Participants With Neutralizing ADAs Against NXT007 At prespecified timepoints from Baseline to Study Completion approximately 3.5 years
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Haemophilia Comprehensive Care Centre Charlotte Maxeke Johannesburg Academic Hospital, Area 454, Room 31, Green Block, York Road, Parktown Johannesburg 2193 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
F. Hoffmann La Roche Ltd Grenzacherstrasse 124 4058 Basel, Switzerland Switzerland 4058 Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor F. Hoffmann La Roche Ltd Grenzacherstrasse 124 4058 Basel, Switzerland Switzerland 4058 Switzerland Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
Chugai Pharmaceutical Co Ltd 1-1 Nihonbashi-Muromachi 2-chome Tokyo Japan
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Johnny Mahlangu johnny.mahlangu@wits.ac.za 0114898435 Charlotte Maxeke Johannesburg Academic Hospital, Area 454, Room 31, Green Block, York Road, Parktown
City Postal code Country Position/Affiliation
Johannesburg 2193 South Africa National PI
Role Name Email Phone Street address
Public Enquiries Johnny Mahlangu johnny.mahlangu@nhls.ac.za 0114898435 Charlotte Maxeke Johannesburg Academic Hospital, Area 454, Room 31, Green Block, York Road, Parktown
City Postal code Country Position/Affiliation
Johannesburg 2193 South Africa National PI
Role Name Email Phone Street address
Scientific Enquiries Johnny Mahlangu johnny.mahlangu@nhls.ac.za 0114898435 Charlotte Maxeke Johannesburg Academic Hospital, Area 454, Room 31, Green Block, York Road, Parktown
City Postal code Country Position/Affiliation
Johannesburg 2193 South Africa National PI
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Roche is committed to external participant-level data sharing with qualified independent researchers. This organizational commitment to transparency is strictly governed by Roche’s Commitment to Transparency of Clinical Study Information and Roche's Global: Policy on Individual Participant Level Data Sharing & Reuse (POL-0300101). Roche confirms its willingness to share de-identified individual participant-level data with qualified independent researchers and organizations upon study completion to foster secondary research and advance scientific and medical knowledge. Standard data sharing statements detailing the specific availability of this individual participant-level data from Roche clinical trials are prepared in alignment with the Roche Pharma Publication Data Sharing Statement Guidance. Additionally, Roche may participate in other collaborative external participant-level data sharing initiatives as outlined in Roche's internal policy, Global: External Sharing of Participant Data for Roche Instigated Collaborations (SOP-0301437). Clinical Study Report Within a year of study completion. Study data may be submitted to government or other health research databases or shared with researchers, government agencies, companies, or other groups that are not participating in this study. These data may be combined with or linked to other data and used for research purposes, to advance science and public health, or for analysis, development, and commercialization of products to treat and diagnose disease. In addition, redacted Clinical Study Reports and/or other summaries of clinical study results may be available in health authority databases for public access, as required by local regulation, and will be provided upon request.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
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Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
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