Hemophilia APhase 3GENEr8-JPNNCT06224907
Phase 3 Study for Efficacy and Safety Outcomes Data in Japanese Patients With Severe Hemophilia A
A Phase 3 study testing Valoctocogene roxaparvovec in people with Hemophilia A, run by BioMarin Pharmaceutical at 4 sites in Japan.
Trial summary
This Phase III clinical study will evaluate the safety and effectiveness of valoctocogene roxaparvovec in Japanese patients with severe hemophilia A. Read more about this study
- Who is it for?
- Ages 18 years and older, men onlyHealthy volunteers can take part
- Conditions the study is for
- Hemophilia A
- What is being tested?
- Valoctocogene roxaparvovec
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 4 sitesJapan
- Study dates
- 25 Dec 2023to Mar 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Japanese males ≥18 years of age with HA and endogenous FVIII activity levels <1 IU/dL as evidenced by medical history, at the time of signing the informed consent
- Must have been on prophylactic FVIII replacement therapy for at least 12 months prior to study entry. High-quality, well-documented historical data concerning bleeding episodes and FVIII usage over the previous 12 months must be available.
- Treated/exposed to FVIII concentrates for a minimum of 150 exposure days.
- Willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any study-related procedures.
- No previous documented history of a detectable FVIII inhibitor, and results from a Bethesda assay or Bethesda assay with Nijmegen modification of less than 0.6 Bethesda Units (BU) or less than 1.0 BU for laboratories with a historical lower sensitivity cutoff for inhibitor detection of 1.0 BU on 2 consecutive occasions at least 1 week apart within the past 12 months (at least 1 of which should be tested at the central laboratory).
- Sexually active participants must agree to use an acceptable method of effective contraception
- Willing to abstain from alcohol consumption for at least the first 52 weeks following BMN 270 infusion.
Who cannot join
- Detectable pre-existing antibodies to the AAV5 capsid.
- Any evidence of active infection or any immunosuppressive disorder, except for human immunodeficiency virus (HIV) infection. HIV-positive participants who meet all other eligibility criteria may be included.
- Significant liver dysfunction
- Most recent, prior FibroScan or liver biopsy showing significant fibrosis
- Evidence of any bleeding disorder not related to HA.
- Platelet count of <100E9/L.
Show all 22Show fewer
- Creatinine ≥1.5 mg/dL.
- Liver cirrhosis of any etiology as assessed by liver ultrasound.
- Chronic or active hepatitis B
- Active hepatitis C
- Active malignancy, except non-melanoma skin cancer
- History of hepatic malignancy
- History of arterial or venous thromboembolic events
- Known inherited or acquired thrombophilia, including conditions associated with increased thromboembolic risk, such as atrial fibrillation
- Treatment with any investigational product (IP) within 30 days or 5 half-lives of the IP prior to the Screening period.
- Any condition that, in the opinion of the investigator or sponsor would prevent the participant from fully complying with the requirements of the study
- Prior treatment with any vector or gene transfer agent.
- Major surgery planned in the 52-week period following the infusion with BMN 270.
- Use of systemic immunosuppressive agents, not including corticosteroids, or live vaccines within 30 days before the BMN 270 infusion.
- Concurrent enrollment in another clinical study unless it is an observational (non-interventional) clinical study that does not interfere with the requirements of the current protocol or have the potential to impact the evaluation of efficacy and safety of BMN 270 and with prior consultation with the medical monitor.
- Known allergy or hypersensitivity to BMN 270 IP formulation.
- Unwilling to receive blood or blood products for treatment of an AE and/or a bleeding episode.
Trial locations and contacts
4 sites in 1 country.
Japan4 sites
Nagoya University Hospital
Aichi, Nagoya, 466-8560
Asahikawa Medical University Hospital
Hokkaido, Asahikawa, 078-8510
Saitama Medical University Hospital
Saitama, Iruma-gun, 350-0495
Tokyo Medical University Hospital
Tokyo, Shinjuku-ku, 160-0023
About this study
Official title: GENEr8-JPN: A Phase 3 Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Japanese Hemophilia A Patients With Residual FVIII Levels ≤ 1 IU/dL Receiving Prophylactic FVIII Infusions
This Phase III clinical study will evaluate the safety and effectiveness of valoctocogene roxaparvovec in Japanese patients with severe hemophilia A.
Read the detailed description
This is a Phase 3, single-arm, open-label study in Japanese hemophilia A (HA) participants with endogenous coagulation factor VIII (FVIII) activity levels <1 IU/dL treated continuously with prophylactic exogenous FVIII for a minimum of 1 year prior to enrollment. Participants will be enrolled at approximately 10 sites in Japan. Participants must have high-quality, well-documented historical data available concerning previous bleeding episodes and exogenous FVIII usage over the previous 12 months in order to be eligible to enroll in the study. Approximately 6 Japanese adult participants with severe HA will receive a 6E13 vg/kg dose of BMN 270 as a single intravenous infusion.
- Conditions
- Hemophilia A
- Being tested
- Valoctocogene roxaparvovec
- Keywords
- Gene Therapy, Clotting Disorders, Blood Disorder, Blood Coagulation Disorders, Inherited Blood Coagulation disorders, Hematologic Diseases, Coagulation Protein Disorders, Hemorrhagic Disorders, Genetic Diseases, Inborn, Factor VIII, Coagulants
- Medical subject headings
- Hemophilia A, Hemostatic Disorders, Hematologic Diseases, Blood Coagulation Disorders, Blood Coagulation Disorders, Inherited, Coagulation Protein Disorders, Hemorrhagic Disorders, Genetic Diseases, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Valoctocogene roxaparvovecBiological
Also called BMN 270, ROCTAVIAN
Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Severe Hemophilia A
| Study group | Role | What they receive |
|---|---|---|
| Valoctocogene roxaparvovec | Experimental | Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg Receives: Biological: Valoctocogene roxaparvovec |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the human coagulation factor VIII (hFVIII) activity, as measured by chromogenic substrate assay, during Weeks 49 to 52 post BMN 270 infusion from Baseline.
The change from baseline in FVIII activity, as measured by chromogenic substrate assay, during Weeks 49 to 52 post-BMN 270 infusion.
Each subject's FVIII activity level during Week 49 to 52 is defined as the median of the values obtained during week 49-52 with the analysis window defined.
Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis. The baseline value is imputed as 1 IU/dL for each subject.
Measured: 52 Weeks
Secondary outcomes (4)
Change in the annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy in the efficacy evaluation period (EEP) ("Post FVIII Prophylaxis to Last Visit") from the Baseline utilization of exogenous FVIII replacement therapy.
The change from baseline in the annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy in the EEP period .
The annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy is defined as Sum of FVIII use (IU/kg) during calculation period/Total number of days during the calculation period ×365.25.
Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis. EEP: From Week 5 post-BMN 270 infusion (Study Day 33) or 3 days post the end of FVIII prophylaxis ), whichever is later, to last visit by the data cut-off for the 1-year analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit").
Measured: Baseline to at least Week 52
Change in the annualized bleeding rate (i.e., number of bleeding episodes per year) requiring exogenous FVIII replacement treatment therapy in the efficacy evaluation period ("Post FVIII Prophylaxis to Last Visit") from Baseline.
ABR for treated bleeds=Number of bleeding episodes for treated bleeds during the calculation period/total number of days during the calculation period * 365.25 Bleeds that were treated with FVIII replacement therapy (recorded as "treatment for bleed") within 72 hours and were not associated with surgery or a procedure were included.
Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis. EEP: From Week 5 post-BMN 270 infusion (Study Day 33) or 3 days post the end of FVIII prophylaxis , whichever is later, to last visit by the data cut-off for the 1-year analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit").
Measured: Baseline to at least Week 52
Change from Baseline in Hemophilia-Specific Health-Related Quality of Life Questionnaire for Adults (Haemo-QoL-A) total score, physical functioning, role functioning, and consequences of bleeding domain scores at Week 52 of study post-BMN 270 infusion
The change from baseline (assuming no treatment for severe hemophilia A) in Haemo-Qol-A score, at week 52 post-BMN 270 infusion. The Haemo-Qol-A questionnaire is a fit for purpose hemophilia-specific health related quality of life (HRQoL) questionnaire for adults consisting of 41 items covering six domains (Physical Functioning, Role Functioning, Worry, Consequences of Bleeding, Emotional Impact and Treatment Concerns).The Haemo-Qol-A items are answered on a 6-point Likert scale ranging from 0 (none of the time) to 5 (all of the time).The recall period for the Haemo-Qol-A is one month (4-weeks).
The Haemo-Qol-A physical functioning domain score is an average of each item value within a domain. The range of domain scores is 0 to 5; higher scores mean better HRQoL or less impairment for the domain. The physical functioning domain score is transformed to a 0 (minimum) to 100 (maximum) scale with higher scores indicating a better or less impaired haemophilia-related physical functioning
Measured: Baseline to Week 52
Change from Baseline in the Haemo-QoL-A worry, emotional impact, and treatment concern domain scores at Week 52 of the study post-BMN 270 infusion.
The change from baseline (assuming no treatment for severe hemophilia A) in Haemo-Qol-A score, at week 52 post-BMN 270 infusion. The Haemo-Qol-A questionnaire is a fit for purpose hemophilia-specific health related quality of life (HRQoL) questionnaire for adults consisting of 41 items covering six domains (Physical Functioning, Role Functioning, Worry, Consequences of Bleeding, Emotional Impact and Treatment Concerns).The Haemo-Qol-A items are answered on a 6-point Likert scale ranging from 0 (none of the time) to 5 (all of the time).The recall period for the Haemo-Qol-A is one month (4-weeks)
Measured: Baseline to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2024
- Study start25 Dec 2023
- Primary completion16 Apr 2025
- Study completionMar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- More trials run by BioMarin PharmaceuticalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- BioMarin Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, MD, Study director, BioMarin Pharmaceutical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06224907
- Sponsor's protocol ID
- 270-304
- Acronym
- GENEr8-JPN
- Status last verified
- Mar 2026
- First submitted
- 16 Jan 2024
- Last updated
- 19 Mar 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GENEr8-JPN: A Phase 3 Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Japanese Hemophilia A Patients With Residual FVIII Levels ≤ 1 IU/dL Receiving Prophylactic FVIII Infusions
- ClinicalTrials.gov ID
- NCT06224907
- Acronym / sponsor ID
- GENEr8-JPN / 270-304
- Conditions
- Hemophilia A
- Keywords
- Gene Therapy, Clotting Disorders, Blood Disorder, Blood Coagulation Disorders, Inherited Blood Coagulation disorders, Hematologic Diseases, Coagulation Protein Disorders, Hemorrhagic Disorders
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- 25 Dec 2023 (actual)
- Primary completion
- 16 Apr 2025 (actual)
- Study completion
- Mar 2029 (estimated)
- First posted
- 25 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase III clinical study will evaluate the safety and effectiveness of valoctocogene roxaparvovec in Japanese patients with severe hemophilia A.
Detailed description
This is a Phase 3, single-arm, open-label study in Japanese hemophilia A (HA) participants with endogenous coagulation factor VIII (FVIII) activity levels <1 IU/dL treated continuously with prophylactic exogenous FVIII for a minimum of 1 year prior to enrollment. Participants will be enrolled at approximately 10 sites in Japan. Participants must have high-quality, well-documented historical data available concerning previous bleeding episodes and exogenous FVIII usage over the previous 12 months in order to be eligible to enroll in the study. Approximately 6 Japanese adult participants with severe HA will receive a 6E13 vg/kg dose of BMN 270 as a single intravenous infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Valoctocogene roxaparvovec | Experimental | Biological: Valoctocogene roxaparvovecSingle administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Japanese males ≥18 years of age with HA and endogenous FVIII activity levels <1 IU/dL as evidenced by medical history, at the time of signing the informed consent
- Must have been on prophylactic FVIII replacement therapy for at least 12 months prior to study entry. High-quality, well-documented historical data concerning bleeding episodes and FVIII usage over the previous 12 months must be available.
- Treated/exposed to FVIII concentrates for a minimum of 150 exposure days.
- Willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any study-related procedures.
- No previous documented history of a detectable FVIII inhibitor, and results from a Bethesda assay or Bethesda assay with Nijmegen modification of less than 0.6 Bethesda Units (BU) or less than 1.0 BU for laboratories with a historical lower sensitivity cutoff for inhibitor detection of 1.0 BU on 2 consecutive occasions at least 1 week apart within the past 12 months (at least 1 of which should be tested at the central laboratory).
Key exclusion criteria (22 listed)
- Detectable pre-existing antibodies to the AAV5 capsid.
- Any evidence of active infection or any immunosuppressive disorder, except for human immunodeficiency virus (HIV) infection. HIV-positive participants who meet all other eligibility criteria may be included.
- Significant liver dysfunction
- Most recent, prior FibroScan or liver biopsy showing significant fibrosis
- Evidence of any bleeding disorder not related to HA.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Valoctocogene roxaparvovecAlso: BMN 270, ROCTAVIANAdeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Severe Hemophilia A | Biological | Valoctocogene roxaparvovec |
Primary outcome
Change in the human coagulation factor VIII (hFVIII) activity, as measured by chromogenic substrate assay, during Weeks 49 to 52 post BMN 270 infusion from Baseline.
Time frame: 52 Weeks
The change from baseline in FVIII activity, as measured by chromogenic substrate assay, during Weeks 49 to 52 post-BMN 270 infusion. Each subject's FVIII activity level during Week 49 to 52 is defined as the median of the values obtained during week 49-52 with the analysis window defined. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis. The baseline value is imputed as 1 IU/dL for each subject.
4 secondary outcomes
Change in the annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy in the efficacy evaluation period (EEP) ("Post FVIII Prophylaxis to Last Visit") from the Baseline utilization of exogenous FVIII replacement therapy.
Time frame: Baseline to at least Week 52
Change in the annualized bleeding rate (i.e., number of bleeding episodes per year) requiring exogenous FVIII replacement treatment therapy in the efficacy evaluation period ("Post FVIII Prophylaxis to Last Visit") from Baseline.
Time frame: Baseline to at least Week 52
Change from Baseline in Hemophilia-Specific Health-Related Quality of Life Questionnaire for Adults (Haemo-QoL-A) total score, physical functioning, role functioning, and consequences of bleeding domain scores at Week 52 of study post-BMN 270 infusion
Time frame: Baseline to Week 52
Change from Baseline in the Haemo-QoL-A worry, emotional impact, and treatment concern domain scores at Week 52 of the study post-BMN 270 infusion.
Time frame: Baseline to Week 52
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2026.
Related trials for Hemophilia A
Not yet recruitingObservational study
A Study to Describe Patient REal-world FitusiRan ExpeRience
Hemophilia A or B
RecruitingPhase 3
Open-Label Extension Study of Marstacimab in Hemophilia Participants With or Without Inhibitors
Hemophilia A, Hemophilia B
RecruitingObservational study
An Observational Study to Learn More About How Well Damoctocog Alfa Pegol Works in Previously Treated Children With Hemophilia A
Hemophilia A
RecruitingPhase 3
A Clinical Study to Evaluate the Effects of NXT007 Compared to Factor VIII Prophylaxis in Participants With Hemophilia A
Hemophilia A
Active, not recruitingPhase 4
A Study to Evaluate Overall Health, Physical Activity, and Joint Outcomes in Participants With Severe or Moderate Hemophilia A Without Factor VIII Inhibitors on Emicizumab Prophylaxis
Severe Hemophilia A, Moderate Hemophilia A
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor, MD study director
BioMarin Pharmaceutical
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Valoctocogene roxaparvovec in people with Hemophilia A, run by BioMarin Pharmaceutical at 4 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the human coagulation factor VIII (hFVIII) activity, as measured by chromogenic substrate assay, during Weeks 49 to 52 post BMN 270 infusion from Baseline. (time frame: 52 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2026.