Back to resultsDose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors
Primary Purpose
Adeno-Associated Virus (AAV), Blood Coagulation Disorder, Blood Coagulation Disorders, Inherited
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SPK-8016
Sponsored by
About this trial
This is an interventional treatment trial for Adeno-Associated Virus (AAV)
Eligibility Criteria
Inclusion Criteria for Part 1:
- Be male and ≥18 years of age;
Have clinically severe hemophilia A, defined as:
- <1% (<1 IU/dL) endogenous FVIII activity levels as historically documented by a certified laboratory or screening data results; OR
- 1-2% (1-2 IU/dL) endogenous FVIII activity levels and > 10 bleeding events per year (in the last 52 weeks prior to screening); OR
- 1-2% (1-2 IU/dL) endogenous FVIII activity levels and on prophylaxis;
- Have had >150 exposure days (EDs) to any recombinant and/or plasma-derived FVIII concentrates or cryoprecipitates
- Have no prior history of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration
- Have no measurable inhibitor against FVIII as assessed by central laboratory, have no confirmed history of clinically significant FVIII inhibitor, and no clinical signs or symptoms of decreased response to FVIII administration (Note: family history of inhibitors will not exclude study participation)
- Agree to use reliable barrier contraception after the administration of SPK-8016 until notified by the Investigator.
Exclusion Criteria for Part 1:
- Have active hepatitis B or C
- Have significant underlying liver disease.
- Have serological evidence of HIV-1 or HIV-2 with CD4 counts ≤200/mm3. Participants who are HIV-positive and stable, with an adequate CD4 count (>200/mm3) and undetectable viral load, and are on an antiretroviral drug regimen are eligible to enroll
- Have detectable antibodies reactive with AAV-Spark capsid
- Have history of chronic infection or other chronic disease
- Have been dosed in a previous gene therapy research trial within the last 52 weeks or with an investigational drug within the last 12 weeks
- Any concurrent clinically significant major disease (such as liver abnormalities or type I diabetes) or other condition that, in the opinion of the Investigator and/or Sponsor, makes the subject unsuitable for participation in the study;
- Unable or unwilling to comply with the schedule of visits and study assessments described in the clinical protocol.
Sites / Locations
- Orthopaedic Institute for Children
- Illinois Bleeding and Clotting Disorders Institute
- University of Michigan
- Mississippi Center for Advanced Medicine
- Weill Cornell Medicine
- Oregon Health & Science University
- Penn State Health
- Children's Hospital of Philadelphia
- Jefferson University Hospitals
- Hemophilia Center of Western Pennsylvania
- Virginia Commonwealth University School of Medicine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
SPK-8016
Arm Description
All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8016.
Outcomes
Primary Outcome Measures
Number of study-related adverse events, including clinically significant abnormal laboratory values.
Adverse events.
Occurrence of hepatic transaminase elevation requiring immunosuppression.
Number of incidences of hepatic transaminase elevation where immunosuppression is required.
Number of bleeding events (spontaneous and traumatic) after vector administration.
Bleeding events.
Number of FVIII infusions after vector administration.
FVIII infusions.
Peak and steady-state FVIII activity levels.
Peak and steady-state FVIII activity levels assessed by coagulation clotting assays.
Secondary Outcome Measures
Vector shedding of SPK-8016 in bodily fluids.
Vector shedding.
Incidence of immune response to AAV capsid protein and transgene product.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03734588
Brief Title
Dose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors
Official Title
Dose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 30, 2019 (Actual)
Primary Completion Date
March 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Spark Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
SPK-8016 is in development for the treatment of patients with inhibitors to FVIII. This Phase 1/2, open-label, non-randomized, dose-finding study is part one of a planned two part study of SPK-8016. Part one will evaluate the safety, efficacy, and tolerability of SPK-8016 in adult males with clinically severe hemophilia A and no measurable inhibitor against FVIII. Data obtained from Part 1 will inform the study design and dose selection for Part 2 in patients with FVIII inhibitors.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adeno-Associated Virus (AAV), Blood Coagulation Disorder, Blood Coagulation Disorders, Inherited, Coagulation Protein Disorders, Factor VIII (FVIII), Factor VIII (FVIII) Deficiency, Factor VIII (FVIII) Gene, Factor VIII (FVIII) Protein, Genetic Diseases, Inborn, Genetic Diseases, X-Linked, Gene Therapy, Gene Transfer, Hematologic Diseases, Hemorrhagic Disorders, Recombinant, Vector, Inhibitors
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
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SPK-8016
Arm Type
Experimental
Arm Description
All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8016.
Intervention Type
Genetic
Intervention Name(s)
SPK-8016
Intervention Description
adeno-associated viral vector
Primary Outcome Measure Information:
Title
Number of study-related adverse events, including clinically significant abnormal laboratory values.
Description
Adverse events.
Time Frame
52 weeks
Title
Occurrence of hepatic transaminase elevation requiring immunosuppression.
Description
Number of incidences of hepatic transaminase elevation where immunosuppression is required.
Time Frame
52 weeks
Title
Number of bleeding events (spontaneous and traumatic) after vector administration.
Description
Bleeding events.
Time Frame
52 weeks
Title
Number of FVIII infusions after vector administration.
Description
FVIII infusions.
Time Frame
52 weeks
Title
Peak and steady-state FVIII activity levels.
Description
Peak and steady-state FVIII activity levels assessed by coagulation clotting assays.
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Vector shedding of SPK-8016 in bodily fluids.
Description
Vector shedding.
Time Frame
52 weeks
Title
Incidence of immune response to AAV capsid protein and transgene product.
Time Frame
52 weeks
10. Eligibility
Sex
Male
Gender Based
Yes
Gender Eligibility Description
Genetically male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria for Part 1:
Be male and ≥18 years of age;
Have clinically severe hemophilia A, defined as:
<1% (<1 IU/dL) endogenous FVIII activity levels as historically documented by a certified laboratory or screening data results; OR
1-2% (1-2 IU/dL) endogenous FVIII activity levels and > 10 bleeding events per year (in the last 52 weeks prior to screening); OR
1-2% (1-2 IU/dL) endogenous FVIII activity levels and on prophylaxis;
Have had >150 exposure days (EDs) to any recombinant and/or plasma-derived FVIII concentrates or cryoprecipitates
Have no prior history of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration
Have no measurable inhibitor against FVIII as assessed by central laboratory, have no confirmed history of clinically significant FVIII inhibitor, and no clinical signs or symptoms of decreased response to FVIII administration (Note: family history of inhibitors will not exclude study participation)
Agree to use reliable barrier contraception after the administration of SPK-8016 until notified by the Investigator.
Exclusion Criteria for Part 1:
Have active hepatitis B or C
Have significant underlying liver disease.
Have serological evidence of HIV-1 or HIV-2 with CD4 counts ≤200/mm3. Participants who are HIV-positive and stable, with an adequate CD4 count (>200/mm3) and undetectable viral load, and are on an antiretroviral drug regimen are eligible to enroll
Have detectable antibodies reactive with AAV-Spark capsid
Have history of chronic infection or other chronic disease
Have been dosed in a previous gene therapy research trial within the last 52 weeks or with an investigational drug within the last 12 weeks
Any concurrent clinically significant major disease (such as liver abnormalities or type I diabetes) or other condition that, in the opinion of the Investigator and/or Sponsor, makes the subject unsuitable for participation in the study;
Unable or unwilling to comply with the schedule of visits and study assessments described in the clinical protocol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tiffany Chang, MD
Organizational Affiliation
Spark Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Orthopaedic Institute for Children
City
Los Angeles
State/Province
California
ZIP/Postal Code
90007
Country
United States
Facility Name
Illinois Bleeding and Clotting Disorders Institute
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61615
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Mississippi Center for Advanced Medicine
City
Madison
State/Province
Mississippi
ZIP/Postal Code
39110
Country
United States
Facility Name
Weill Cornell Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Penn State Health
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Jefferson University Hospitals
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Hemophilia Center of Western Pennsylvania
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Virginia Commonwealth University School of Medicine
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23219
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Dose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors
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