Clinical trial NCT03734588: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: Spark Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-11-08
Enrollment: 4
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: 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 to evaluate the safety, efficacy, and tolerability of SPK-8016 in adult males with severe hemophilia A and no measurable inhibitor against FVIII.


Eligibility criteria: Inclusion Criteria:

1. Be male and ≥18 years of age;
2. Have clinically severe hemophilia A, defined as:

   1. \<1% (\<1 IU/dL) endogenous FVIII activity levels as historically documented by a certified laboratory or screening data results; OR
   2. 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
   3. 1-2% (1-2 IU/dL) endogenous FVIII activity levels and on prophylaxis;
3. Have had \>150 exposure days (EDs) to any recombinant and/or plasma-derived FVIII concentrates or cryoprecipitates
4. Have no prior history of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration
5. 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)
6. Agree to use reliable barrier contraception after the administration of SPK-8016 until notified by the Investigator.

Exclusion Criteria:

1. Have active hepatitis B or C
2. Have significant underlying liver disease.
3. 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
4. Have detectable antibodies reactive with AAV-Spark capsid
5. Have history of chronic infection or other chronic disease
6. 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
7. 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;
8. Unable or unwilling to comply with the schedule of visits and study assessments described in the clinical protocol.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to week 52
measure: Number of Participants With Hepatic Transaminase Elevation Requiring Immunosuppression.
timeFrame: Up to week 52
measure: Peak FVIII Activity Levels Assessed by Coagulation Clotting Assays
timeFrame: Up to week 52
measure: Steady-state FVIII Activity Levels Assessed by Coagulation Clotting Assays
timeFrame: Up to week 52
measure: Number of Bleeding Events (Spontaneous and Traumatic) Since 28 Day Post Vector Administration
timeFrame: From 28 days post vector administration up to week 52
measure: Annualized Infusion Rate
timeFrame: From 28 days post vector administration up to week 52
Secondary outcomes:
measure: Time to Achieve Steady-state FVIII Activity Levels
timeFrame: Up to week 52
measure: Number of Participants With Vector-shedding of SPK-8016 in Bodily Fluids
timeFrame: Up to week 52
measure: Number of Participants With Immune Responses to AAV Capsid Protein and BDD-hFVIII Transgene
timeFrame: Up to week 52
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Orthopaedic Institute for Children
state: California
city: Peoria
country: United States
facility: Illinois Bleeding and Clotting Disorders Institute
state: Illinois
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Madison
country: United States
facility: Mississippi Center for Advanced Medicine
state: Mississippi
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State Health
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson University Hospitals
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Hemophilia Center of Western Pennsylvania
state: Pennsylvania
city: Richmond
country: United States
facility: Virginia Commonwealth University School of Medicine
state: Virginia
Study officials:
affiliation: Spark Therapeutics, Inc.
name: Tiffany Chang, MD
role: STUDY_DIRECTOR
References: