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

Sponsor

BioMarin Pharmaceutical (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04684940

Collaborator

(none)

Enrollment

Locations

Arm

97.7

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Hemophilia A With Inhibitor Hemophilia A With Anti Factor VIII	Biological: Valoctocogene roxaparvovec	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 10, 2020

Anticipated Primary Completion Date :

Feb 1, 2029

Anticipated Study Completion Date :

Feb 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Valoctocogene roxaparvovec Open Label Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg in Active Inhibitor Population (Part A) and Prior Inhibitor Population (Part B).	Biological: Valoctocogene roxaparvovec Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A Other Names: BMN 270

Arm

Intervention/Treatment

Experimental: Valoctocogene roxaparvovec Open Label

Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg in Active Inhibitor Population (Part A) and Prior Inhibitor Population (Part B).

Biological: Valoctocogene roxaparvovec

Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A

Other Names:

BMN 270

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Change of the median Factor VIII activity. [60 months]
Changes in the median Factor VIII activity (IU/mL) after administration of BMN 270 which will be measured using the chromogenic FVIII assay.
A change in Factor VIII inhibitor titer (Part A) after administration of BMN 270. [60 months]
FVIII inhibitor titer will be measured using a chromogenic Nijmegen-Bethesda assay.
Absence of recurrence of Factor VIII inhibitors (Part B) after administration of BMN 270. [60 months]
FVIII inhibitor titer will be measured using a chromogenic Nijmegen-Bethesda assay.
Change in the annualized utilization of hemophilia therapy after administration of BMN 270 [60 months]
Change in the annualized number of bleeding episodes requiring exogenous hemophilia therapy after administration of BMN 270. [60 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
History of a positive inhibitor result with the first positive result in the last 12 months.

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.

Prophylactic or on-demand hemophilia therapy in the last 12 months. Bleeding, inhibitor & hemophilia therapy Hx over previous 12 months.
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.
Willing to abstain from consumption of alcohol for at least the first 52 weeks following BMN 270 infusion.

Exclusion Criteria:

Detectable pre-existing antibodies to the AAV5 capsid.
Any evidence of active infection or any immunosuppressive disorder; patients with HIV infection and undetectable viral load are not excluded.
Currently undergoing, or plan to receive during the study, immune tolerance induction therapy or prophylaxis with FVIII (Part A only).
Significant renal dysfunction or liver dysfunction, infection or history of hepatic malignancy.
Evidence of any bleeding disorder not related to hemophilia A.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
2	UC Davis Hemophilia Treatment Center	Sacramento	California	United States	95817
3	Queen Elizabeth Hospital	Birmingham		United Kingdom
4	Guy's and St Thomas' NHS Foundation Trust	London		United Kingdom
5	Royal Free Hospital	London		United Kingdom