Trial no.:	PACTR202607919848121	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 EMICIZUMAB 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 Emicizumab Prophylaxis in people with Hemophilia A

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 emicizumab prophylaxis in people age 12 years and older with severe or moderate congenital hemophilia A (HA) without factor VIII (FVIII) inhibitors or with HA of any severity (severe, moderate, and mild) with FVIII inhibitors. People with a diagnosis of mild HA may be eligible to participate if they have FVIII inhibitors resulting in chronic ( > 12 months) reduction of endogenous FVIII levels to <5 IU/dL. Treatment options for HA include FVIII replacement or non-factor therapies, both of which can offer significant improvement in bleed management and protection. However, many in this population remain at risk of bleeding and require additional specialist management at times. There is thus a need for a convenient SC treatment for HA that offers superior bleed protection and normalization of hemostatic potential versus current standard of care (SoC) throughout the dosing interval. Primary objectives: To evaluate the efficacy of NXT007 prophylaxis compared with emicizumab prophylaxis based on the non-inferiority assessment of treated bleeds. Secondary objectives: to evaluate the efficacy of NXT007 prophylaxis compared with emicizumab prophylaxis based on the superiority assessment of treated bleeds, to evaluate the efficacy of NXT007 prophylaxis compared with emicizumab prophylaxis based on non-inferiority and superiority assessment in all bleeds, treated joint bleed and treated spontaneous bleeds, to evaluate the efficacy of NXT007 prophylaxis compared with emicizumab prophylaxis based on superiority assessment of health-related quality of life as assessed through use of the CATCH questionnaire (treatment burden domain in the adult version). To evaluate the efficacy of NXT007 prophylaxis compared with emicizumab prophylaxis for other secondary endpoints.

Type of trial

RCT

Acronym (If the trial has an acronym then please provide)

ZEBRHA 2

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

25/08/2031

Actual Last follow-up date

15/10/2030

Anticipated target sample size (number of participants)

8

Actual target sample size (number of participants)

Recruitment status

Not yet recruiting

Publication URL

Secondary Ids	Issuing authority/Trial register
DOH-27-072026-4970	SANCTR
BO45887	F. HoffmannLa Roche Ltd

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	Permuted block randomization	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 Test Product	Participants will receive loading doses of NXT007 administered subcutaneously on Day 1 and Day 15 at Month 1 and thereafter will receive monthly SC maintenance doses. After the main study treatment period, which will be a minimum of 7 months, participants in the NXT007 group 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 but may be longer depending on the duration of recruitment for the study.	NXT007 will be administered subcutaneously via an autoinjector.	4
Control Group	Emicizumab Comparator group	Participants may self-administer emicizumab according to the local practice if they have received proper training. Participants who were not treated with emicizumab prior to study start will begin treatment with loading doses of emicizumab 3 mg/kg SC weekly (QW) for 4 weeks in Month 1, administered as per local practice on Days 1, 8, 15, and 22. Participants who were treated with emicizumab prior to study start will not require loading doses of emicizumab and will continue emicizumab at maintenance doses of either 1.5 mg/kg SC weekly (QW), 3 mg/kg SC every 2 weeks (Q2W), or 6 mg/kg SC every 4 weeks (Q4W) (maintenance regimen as agreed between investigator and participant).	The total duration of study participation for a participant is expected to be approximately 3.5 years but may be longer depending on the duration of recruitment for the study.	Active Comparator	4	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 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	• 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	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

22/04/2026

University of the Witwatersrand Human Research Ethics Committee

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

23/06/2026

SAHPRA

Ethics Committee Address
Street address	City	Postal code	Country
Building A Loftus Park 402 Kirkness Street Arcadia	Pretoria	0083	South Africa

OUTCOMES
Type of outcome	Outcome	Timepoint(s) at which outcome measured
Primary Outcome	To evaluate the efficacy of NXT007 prophylaxis compared with emicizumab prophylaxis based on the non inferiority assessment of treated bleeds	From the Month 2 visit until completion of the study
Secondary Outcome	To evaluate the efficacy of NXT007 prophylaxis compared with emicizumab prophylaxis based on non inferiority and superiority assessment in all bleeds, treated joint bleed and treated spontaneous bleeds	From the Month 2 visit until completion of the study
Secondary Outcome	To evaluate the efficacy of NXT007 prophylaxis compared with emicizumab prophylaxis based on non-inferiority and superiority assessment in all bleeds, treated joint bleed and treated spontaneous bleeds.	From the Month 2 visit until completion of the study
Secondary Outcome	To evaluate the efficacy of NXT007 prophylaxis compared with emicizumab prophylaxis based on non-inferiority and superiority assessment in all bleeds, treated joint bleed and treated spontaneous bleeds	From the Month 2 visit until completion of the study
Secondary Outcome	To evaluate the efficacy of NXT007 prophylaxis compared with emicizumab prophylaxis based on superiority assessment of health-related quality of life as assessed through use of the CATCH questionnaire (treatment burden domain in the adult version)	Month 8
Secondary Outcome	To evaluate the efficacy of NXT007 prophylaxis compared with emicizumab prophylaxis for other secondary endpoints	From the month 2 visit until completion of the study
Secondary Outcome	To evaluate the quality of life of participants treated with NXT007 prophylaxis compared with emicizumab prophylaxis as assessed through the use of the CATCH questionnaires (adult and adolescent versions)	Specified timepoints from baseline
Secondary Outcome	To evaluate participants' satisfaction with SC treatment administration as assessed through the use of the TASQ-SC	Specified timepoints from baseline
Secondary Outcome	To evaluate the safety of NXT007 prophylaxis compared with emicizumab prophylaxis	Specified timepoints from baseline
Secondary Outcome	To characterize the pharmacokinetics of NXT007	Specified timepoints from baseline
Secondary Outcome	To evaluate the immunogenicity of NXT007	Specified timepoints from baseline

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 Gauteng, South Africa	Johannesburg	2193	South Africa

FUNDING SOURCES
Name of source	Street address	City	Postal code	Country
F. HoffmannLa Roche Ltd	Grenzacherstrasse 124 4058 Basel	Switzerland	4058	Switzerland

SPONSORS
Sponsor level	Name	Street address	City	Postal code	Country	Nature of sponsor
Primary Sponsor	F. HoffmannLa Roche Ltd	Grenzacherstrasse 124 4058 Basel, Switzerland	Switzerland	4058	Switzerland	Commercial Sector/Industry

COLLABORATORS
Name	Street address	City	Postal code	Country
Chugai Pharmaceuticals Co. Ltd	1-1 Nihonbashi-Muromachi 2-chome, Chuo-ku	Tokyo	103-8324	Japan

CONTACT PEOPLE
Role	Name	Email	Phone	Street address
Principal Investigator	Johnny Ndoni Mahlangu	johhny.mahlangu@wits.ac.za	+27114898435	York Road, Parktown
City	Postal code	Country	Position/Affiliation
Johannesburg	2193	South Africa	National Principal Investigator
Role	Name	Email	Phone	Street address
Public Enquiries	Maphuti Ratau	maphuti.ratau@thermofisher.com	+27116128600	The Woodlands Office Park, Building 15, Woodlands drive, Woodmead
City	Postal code	Country	Position/Affiliation
Johannesburg	2191	South Africa	Country Approval Specialist
Role	Name	Email	Phone	Street address
Scientific Enquiries	Johnny Ndoni Mahlangu	johnny.mahlangu@wits.ac.za	+27114898435	York Road, Parktown
City	Postal code	Country	Position/Affiliation
Johannesburg	2193	South Africa	National Principal Investigator

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 our Global: Policy on Individual Participant Level Data Sharing & Reuse (POL-0300101). Roche confirms it's 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 our 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 our internal policy, Global: External Sharing of Participant Data for Roche Instigated Collaborations (SOP-0301437).	Clinical Study Report	Upon 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
https://www.roche.com/innovation/process/clinical-trials/data-sharing	No
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Result URL Hyperlinks	Link To Protocol
Result URL Hyperlinks

Changes to trial information

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