Clinical trial NCT04684940: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2020-12-28
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 60 months
Secondary outcomes:
measure: Change of the median Factor VIII activity.
timeFrame: 60 months
measure: A change in Factor VIII inhibitor titer (Part A) after administration of BMN 270.
timeFrame: 60 months
measure: Absence of recurrence of Factor VIII inhibitors (Part B) after administration of BMN 270.
timeFrame: 60 months
measure: Change in the annualized utilization of hemophilia therapy after administration of BMN 270
timeFrame: 60 months
measure: Change in the annualized number of bleeding episodes requiring exogenous hemophilia therapy after administration of BMN 270.
timeFrame: 60 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Campinas
country: Brazil
facility: Hemocentro Da UNICAMP
city: Rio De Janeiro
country: Brazil
facility: Arthur De Siqueira Cavalcanti Hematology State Institute
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University - Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Izmir
country: Turkey
facility: Ege University School of Medicine
Study officials:
affiliation: BioMarin Pharmaceutical
name: Medical Monitor, MD
role: STUDY_DIRECTOR
References: