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

Primary Purpose

Hemophilia A With Inhibitor, Hemophilia A With Anti Factor VIII

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Valoctocogene roxaparvovec
Sponsored by
BioMarin Pharmaceutical
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophilia A With Inhibitor focused on measuring Gene Therapy, Clotting Disorders, Blood Disorder, Blood Coagulation Disorders, Inherited Blood Coagulation Disorders, Hematologic Diseases, Coagulation Protein Disorders, Hemorrhagic Disorders, Genetic DIseases, Factor VIII, Coagulants, Hemophilia A, AAV5 vector

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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 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.

  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.

Sites / Locations

  • Children's Hospital Los AngelesRecruiting
  • UC Davis Hemophilia Treatment CenterRecruiting
  • Hemocentro Da UNICAMPRecruiting
  • Fondazione IRCCS Cà Granda Ospedale Maggiore PoliclinicoRecruiting
  • Kyung Hee University Hospital at GangdongRecruiting
  • Kaohsiung Medical University - Chung-Ho Memorial HospitalRecruiting
  • National Taiwan University HospitalRecruiting
  • Queen Elizabeth HospitalRecruiting
  • Guy's and St Thomas' NHS Foundation TrustRecruiting
  • Royal Free HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Valoctocogene roxaparvovec Open Label

Arm Description

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

Outcomes

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.

Secondary Outcome Measures

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.
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.
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.
Change in the annualized utilization of hemophilia therapy after administration of BMN 270
Change in the annualized number of bleeding episodes requiring exogenous hemophilia therapy after administration of BMN 270.

Full Information

First Posted
November 30, 2020
Last Updated
January 3, 2023
Sponsor
BioMarin Pharmaceutical
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1. Study Identification

Unique Protocol Identification Number
NCT04684940
Brief Title
Safety, Tolerability, and Efficacy Study of Valoctocogene Roxaparvovec in Hemophilia A With Active or Prior Inhibitors
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 10, 2020 (Actual)
Primary Completion Date
February 2029 (Anticipated)
Study Completion Date
February 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioMarin Pharmaceutical

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A With Inhibitor, Hemophilia A With Anti Factor VIII
Keywords
Gene Therapy, Clotting Disorders, Blood Disorder, Blood Coagulation Disorders, Inherited Blood Coagulation Disorders, Hematologic Diseases, Coagulation Protein Disorders, Hemorrhagic Disorders, Genetic DIseases, Factor VIII, Coagulants, Hemophilia A, AAV5 vector

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Valoctocogene roxaparvovec Open Label
Arm Type
Experimental
Arm Description
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg in Active Inhibitor Population (Part A) and Prior Inhibitor Population (Part B).
Intervention Type
Biological
Intervention Name(s)
Valoctocogene roxaparvovec
Other Intervention Name(s)
BMN 270
Intervention Description
Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Primary Outcome Measure Information:
Title
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.
Time Frame
60 months
Secondary Outcome Measure Information:
Title
Change of the median Factor VIII activity.
Description
Changes in the median Factor VIII activity (IU/mL) after administration of BMN 270 which will be measured using the chromogenic FVIII assay.
Time Frame
60 months
Title
A change in Factor VIII inhibitor titer (Part A) after administration of BMN 270.
Description
FVIII inhibitor titer will be measured using a chromogenic Nijmegen-Bethesda assay.
Time Frame
60 months
Title
Absence of recurrence of Factor VIII inhibitors (Part B) after administration of BMN 270.
Description
FVIII inhibitor titer will be measured using a chromogenic Nijmegen-Bethesda assay.
Time Frame
60 months
Title
Change in the annualized utilization of hemophilia therapy after administration of BMN 270
Time Frame
60 months
Title
Change in the annualized number of bleeding episodes requiring exogenous hemophilia therapy after administration of BMN 270.
Time Frame
60 months

10. Eligibility

Sex
Male
Gender Based
Yes
Gender Eligibility Description
Biological males only
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Trial Specialist
Phone
1-800-983-4587
Email
medinfo@bmrn.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor, MD
Organizational Affiliation
BioMarin Pharmaceutical
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Individual Site Status
Recruiting
Facility Name
UC Davis Hemophilia Treatment Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Individual Site Status
Recruiting
Facility Name
Hemocentro Da UNICAMP
City
Campinas
Country
Brazil
Individual Site Status
Recruiting
Facility Name
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
City
Milan
Country
Italy
Individual Site Status
Recruiting
Facility Name
Kyung Hee University Hospital at Gangdong
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Kaohsiung Medical University - Chung-Ho Memorial Hospital
City
Kaohsiung
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
National Taiwan University Hospital
City
Taipei
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
Queen Elizabeth Hospital
City
Birmingham
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Guy's and St Thomas' NHS Foundation Trust
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Royal Free Hospital
City
London
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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