Safety, Tolerability, and Efficacy Study of Valoctocogene Roxaparvovec in Hemophilia A With Active or Prior Inhibitors

Hemophilia A With Inhibitor Clinical Trial

— GENEr8-INH  

Official title:

A Phase 1/2 Safety, Tolerability, and Efficacy Study of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A Patients With Active or Prior Inhibitors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04684940
• Other study ID #: 270-205
• Secondary ID: 2019-003213-34
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 10, 2020
• Est. completion date: February 2029

Study information

• Verified date: April 2024
• Source: BioMarin Pharmaceutical
• Contact: Trial Specialist
• Phone: 1-800-983-4587
• Email: medinfo[@]bmrn.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase I/II clinical study will evaluate the safety and efficacy of valoctocogene roxaparvovec in patients with severe haemophilia A and inhibitors to FVIII. Part A of the study will involve subjects who have active inhibitors to FVIII, and Part B involving subjects with a prior history of inhibitors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: February 2029
• Est. primary completion date: February 2029
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Males = 18 years of age with hemophilia A and documented prior residual FVIII activity = 1 IU/dL including, but not limited to, at the time of detected inhibitors, at the time of signing the informed consent.

2. History of a positive inhibitor result with the first positive result at least 12 month prior to Screening.

Part A: Demonstrated no immunological tolerance to exogenous FVIII. Part B:

Demonstrated tolerance to exogenous FVIII and negative FVIII inhibitor screening titer < 0.6 BU.

3. Prophylactic or on-demand hemophilia therapy in the last 12 months. Bleeding, inhibitor & hemophilia therapy Hx over previous 12 months.

4. Sexually active participants must agree to use an acceptable method of effective contraception. Participants must agree to contraception use for at least 12 weeks post-infusion.

5. Willing to abstain from consumption of alcohol for at least the first 52 weeks following BMN 270 infusion.

Exclusion Criteria:

1. Detectable pre-existing antibodies to the AAV5 capsid.

2. Any evidence of active infection or any immunosuppressive disorder; patients with HIV infection and undetectable viral load are not excluded.

3. Currently undergoing, or plan to receive during the study, immune tolerance induction therapy or prophylaxis with FVIII (Part A only).

4. Significant renal dysfunction or liver dysfunction, infection or history of hepatic malignancy.

5. Evidence of any bleeding disorder not related to hemophilia A.

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia A With Anti Factor VIII
• Hemophilia A With Inhibitor

Intervention

Biological:
• Valoctocogene roxaparvovec
Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A

Locations

Country	Name	City	State
Brazil	Hemocentro Da UNICAMP	Campinas
Germany	University Hospital Bonn, Institute of Experimental Hematology and Transfusion Medicine	Bonn
Israel	Chaim Sheba Medical Center	Ramat Gan
Italy	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Milan
Korea, Republic of	Kyung Hee University Hospital at Gangdong	Seoul
Korea, Republic of	Severance Hospital Yonsei University	Seoul
South Africa	Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care Center	Johannesburg
Taiwan	Kaohsiung Medical University - Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London
United Kingdom	Royal Free Hospital	London
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	UC Davis Hemophilia Treatment Center	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Countries where clinical trial is conducted

United States,  Brazil,  Germany,  Israel,  Italy,  Korea, Republic of,  South Africa,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-related adverse events, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 after administration of BMN 270.		60 months
Secondary	Change of the median Factor VIII activity.	Changes in the median Factor VIII activity (IU/mL) after administration of BMN 270 which will be measured using the chromogenic FVIII assay.	60 months
Secondary	A change in Factor VIII inhibitor titer (Part A) after administration of BMN 270.	FVIII inhibitor titer will be measured using a chromogenic Nijmegen-Bethesda assay.	60 months
Secondary	Absence of recurrence of Factor VIII inhibitors (Part B) after administration of BMN 270.	FVIII inhibitor titer will be measured using a chromogenic Nijmegen-Bethesda assay.	60 months
Secondary	Change in the annualized utilization of hemophilia therapy after administration of BMN 270		60 months
Secondary	Change in the annualized number of bleeding episodes requiring exogenous hemophilia therapy after administration of BMN 270.		60 months