Lead-in Study to Collect Prospective Efficacy and Safety Data of Current FVIII Prophylaxis Replacement Therapy in Adult Hemophilia A Participants

• ClinicalTrials.gov Identifier: NCT03876301
• Recruitment Status: Active, not recruiting
• First Posted: March 15, 2019
• Last Update Posted: February 22, 2023
• Sponsor: Spark Therapeutics
• Information provided by (Responsible Party): Spark Therapeutics

Study Description

Brief Summary:

The aim of this prospective, observational study is to establish a dataset on the frequency of bleeding events, as well as other characteristics of bleeding events and FVIII infusions, in patients with clinically severe hemophilia A receiving prophylactic FVIII replacement therapy as standard of care. The data collected from this study may assist in providing baseline information for comparison to the Spark's investigational hemophilia A gene therapy in future Phase 3 studies.

Condition or disease	Intervention/treatment
Blood Coagulation Disorder; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemophilia A; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Hematologic Diseases; Hemorrhagic Disorders; Factor VIII Deficiency	Drug: Standard of Care FVIII Replacement therapy

Study Design

• Study Type: Observational
• Estimated Enrollment: 55 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: A Multi-Center, Observational Study in Males With Hemophilia A
• Actual Study Start Date: January 21, 2019
• Estimated Primary Completion Date: June 2023
• Estimated Study Completion Date: December 2023

Groups and Cohorts

Group/Cohort	Intervention/treatment
Observational Cohort; Adult males with clinically severe hemophilia A, who are negative for neutralizing antibody (NAb) to AAV-Spark200	Drug: Standard of Care FVIII Replacement therapy; There is no investigational product being administered. Subjects will be administering their own standard of care FVIII replacement therapy.

Outcome Measures

Primary Outcome Measures :

1. Number of bleeding events, annualized [ Time Frame: 12 months ]
   Annualized bleeding rate (ABR)

Secondary Outcome Measures :

1. Dose and total FVIIII consumption [ Time Frame: 12 months ]
   Total FVIII replacement therapy consumption and the corresponding dose
2. Annualized number of infusions (AIR) [ Time Frame: 12 months ]
   Number of reported infusions over the study period

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Genetically male
• Sampling Method: Non-Probability Sample

Study Population

Adult males with clinically severe hemophilia A (i.e., ≤2% IU/dL FVIII activity level), who meet eligibility criteria for neutralizing antibody (NAb) to AAV-Spark200.

Criteria

Inclusion Criteria:

1. Able and willing to provide written informed consent.
2. Males ≥18 years of age.
3. Clinically severe hemophilia A
4. Previous exposure to FVIII therapy
5. No prior history of hypersensitivity or anaphylaxis associated with an FVIII or intravenous immunoglobulin administration.
6. No measurable inhibitor against FVIII
7. Willing to participate and receive treatment in a future Spark hemophilia A gene therapy study.

Exclusion Criteria:

1. Documented active hepatitis B or C within the past 12 months of Screening
2. Currently on antiviral therapy to treat hepatitis B or C;
3. Documented significant liver disease within the past 6 months of Screening
4. Have serological evidence of HIV-1 or HIV-2
5. Anti-AAV-Spark 200 neutralizing titers ≥1:1
6. Previously received SPK-8011;
7. Previously dosed with any investigational or approved gene therapy product at any time or treated with an investigational drug within the last 12 weeks;
8. Planned surgical procedure in the next 12 months requiring FVIII prophylactic treatment.
9. Any history of chronic infection or other chronic disease, concurrent clinically significant major disease (such as liver abnormalities or type I diabetes) including active malignancy, except for non-melanoma skin cancer, any other condition or any other unspecified reasons that, in opinion of the Investigator or Sponsor, makes the participant unsuitable for participation and dosing in a future clinical study for Spark's hemophilia A gene therapy.
10. Unable or unwilling to comply with the schedule of visits and/or study assessments described in the protocol.

Contacts and Locations

Locations

United States, California

University of California San Francisco

San Francisco, California, United States, 94117

United States, Florida

University of Florida

Gainesville, Florida, United States, 32610

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Michigan

Children's Hospital of Michigan

Detroit, Michigan, United States, 48201

United States, Mississippi

Mississippi Center for Advanced Medicine

Madison, Mississippi, United States, 39110

United States, Washington

Bloodworks Northwest

Seattle, Washington, United States, 98104

Australia, Victoria

The Alfred Hospital

Melbourne, Victoria, Australia, 3004

Australia, Western Austrailia

Fiona Stanley Hospital

Murdoch, Western Austrailia, Australia, 6150

Canada, British Columbia

Providence Hematology/St. Paul's Hosptial

Vancouver, British Columbia, Canada, V621Y6

Canada, Ontario

McMaster University / Royal Prince Alfred Hospital

Hamilton, Ontario, Canada, L8N3Z5

Thailand

Ramathibodi Hospital, Mahidol University

Bangkok, Thailand, 10400

Sponsors and Collaborators

Spark Therapeutics

Investigators

• Principal Investigator: Spencer K Sullivan, MD; Mississippi Center for Advanced Medicine

More Information

• Responsible Party: Spark Therapeutics
• ClinicalTrials.gov Identifier: NCT03876301
• Other Study ID Numbers: SPK-8011-301
• First Posted: March 15, 2019
• Last Update Posted: February 22, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Spark Therapeutics:

Factor VIII; Factor VIII Protein; Recombinant

Additional relevant MeSH terms:

Hemostatic Disorders; Hemophilia A; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Coagulation Protein Disorders; Blood Coagulation Disorders, Inherited; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Disease; Pathologic Processes; Vascular Diseases; Cardiovascular Diseases