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

A Multi-Center, Observational Study in Males With Hemophilia A

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.

Study Overview

• Status: Completed
• Conditions: Hematologic Diseases; Hemophilia A; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorder; Factor VIII Deficiency
• Intervention / Treatment: Drug: Standard of Care FVIII Replacement therapy

• Study Type: Observational
• Enrollment (Actual): 25

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
  • Western Austrailia
    • Murdoch, Western Austrailia, Australia, 6150
      • Fiona Stanley Hospital
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V621Y6
      • Providence Hematology/St. Paul's Hosptial
  • Ontario
    • Hamilton, Ontario, Canada, L8N3Z5
      • McMaster University / Royal Prince Alfred Hospital
• Thailand
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital, Mahidol University
• United States
  • California
    • San Francisco, California, United States, 94117
      • University of California San Francisco
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • Mississippi
    • Madison, Mississippi, United States, 39110
      • Mississippi Center for Advanced Medicine
  • Washington
    • Seattle, Washington, United States, 98104
      • Bloodworks Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of bleeding events, annualized	Annualized bleeding rate (ABR)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose and total FVIIII consumption	Total FVIII replacement therapy consumption and the corresponding dose	12 months
Annualized number of infusions (AIR)	Number of reported infusions over the study period	12 months

Collaborators and Investigators

• Sponsor: Spark Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2019
• Primary Completion (Actual): May 2, 2023
• Study Completion (Actual): May 2, 2023

Study Registration Dates

• First Submitted: March 11, 2019
• First Submitted That Met QC Criteria: March 13, 2019
• First Posted (Actual): March 15, 2019

Study Record Updates

• Last Update Posted (Actual): July 10, 2023
• Last Update Submitted That Met QC Criteria: July 6, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Factor VIII; Recombinant; Factor VIII Protein
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hemostatic Disorders; Hemophilia A; Blood Coagulation Disorders; Hematologic Diseases; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Coagulation Protein Disorders; Blood Coagulation Disorders, Inherited
• Other Study ID Numbers: SPK-8011-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No