GENEr8-JPN: Phase 3 study for efficacy and safety outcomes data in Japanese patients with severe hemophilia A

JRCT ID: jRCT2033230441

Registered date:09/11/2023

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Hemophilia A
• Date of first enrollment: 06/01/2024
• Target sample size: 6
• Study type: Interventional

Intervention(s)

IMP: BMN 270
Each participant will receive a single intravenous infusion of BMN 270 at 6E13 vg/kg. The volume of infusion will depend on the weight of the participants.

Outcome(s)

• 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.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Male

Include criteria

1. 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.
2. 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.
3. Treated/exposed to FVIII concentrates for a minimum of 150 exposure days.
4. 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.
5. 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).
6. Sexually active participants must agree to use an acceptable method of effective contraception (taking oral hormone contraceptives for female partner and using male condoms or using intrauterine device in female partner). Only contraceptive methods approved in Japan are acceptable and effective methods of contraception in this clinical study. Participants must agree to contraception use for at least 12 weeks post-infusion; after 12 weeks, participants may stop contraception use only if they have had 3 consecutive semen samples with viral vector DNA below the limit of detection.
7. Willing to abstain from alcohol consumption for at least the first 52 weeks following BMN 270 infusion.

Exclude criteria

1. Detectable pre-existing antibodies to the AAV5 capsid.
2. 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 if they have a CD4 count >200/ cubic millimeter and an undetectable viral load (unquantifiable viral load as defined as less than the limit of quantification defined by the testing laboratory assay is permitted) while receiving an antiretroviral therapy (ART) regimen that does not contain efavirenz or another potentially hepatotoxic ART.
3. Significant liver dysfunction with any of the following abnormal laboratory results:
- ALT >1.25 x upper limit of normal (ULN);
- Aspartate aminotransferase (AST) >1.25 x ULN;
- Gamma-glutamyltransferase (GGT) >1.25 x ULN;
- Total bilirubin >1.25 x ULN;
- Alkaline phosphatase >1.25 x ULN; or International normalized ratio (INR) >=1.4.
Participants whose liver laboratory assessments fall outside of these ranges may undergo repeat testing of the entire liver test (LT) panel within the same Screening window and, if eligibility criteria are met on retest, may be enrolled after confirmation by the medical monitor.
4. Most recent, prior FibroScan or liver biopsy showing significant fibrosis of 3 or 4 as rated on a scale of 0 to 4 on the Batts-Ludwig (Batts 1995) or METAVIR (Bedossa 1996) scoring systems, or an equivalent grade of fibrosis if an alternative scale is used.
5. Evidence of any bleeding disorder not related to HA.
6. Platelet count of <100E9/L.
7. Creatinine >=1.5 mg/dL.
8. Liver cirrhosis of any etiology as assessed by liver ultrasound.
9. Chronic or active hepatitis B as evidenced by positive serology testing (hepatitis B surface antigen [HBsAg], hepatitis B surface antibody [HBsAb], and hepatitis B core antibody [HBcAb]) and confirmatory HBV DNA testing. Refer to the Centers for Disease Control table for the interpretation of serological test results in the Laboratory Manual.
10. Active hepatitis C as evidenced by detectable hepatitis C virus (HCV) ribonucleic acid (RNA) or currently on antiviral therapy.
11. Active malignancy, except non-melanoma skin cancer.
12. History of hepatic malignancy.
13. History of arterial or venous thromboembolic events (eg, deep vein thrombosis, non-hemorrhagic stroke, pulmonary embolism, myocardial infarction, arterial embolus), with the exception of catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing.
14. Known inherited or acquired thrombophilia, including conditions associated with increased thromboembolic risk, such as atrial fibrillation.
15. Treatment with any investigational product (IP) within 30 days or 5 half-lives of the IP prior to the Screening period. For participants who have received a prior IP, all ongoing AEs experienced while receiving that IP must have resolved prior to Screening for this study.
16. Any condition that, in the opinion of the investigator or sponsor would prevent the participant from fully complying with the requirements of the study (including possible corticosteroid treatment outlined in the protocol) and/or would impact or interfere with evaluation and interpretation of participant safety or efficacy result.
17. Prior treatment with any vector or gene transfer agent.
18. Major surgery planned in the 52-week period following the infusion with BMN 270.
19. Use of systemic immunosuppressive agents, not including corticosteroids, or live vaccines within 30 days before the BMN 270 infusion.
20. 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.
21. Known allergy or hypersensitivity to BMN 270 IP formulation.
22. Unwilling to receive blood or blood products for treatment of an AE and/or a bleeding episode.

Related Information

• Primary Sponsor: Osmond Dane
• Secondary ID(s): NCT06224907