Dose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors

Sponsor

Spark Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03734588

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

2.1

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
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	Genetic: SPK-8016	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Dose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors

Actual Study Start Date :

Jan 30, 2019

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SPK-8016 All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8016.	Genetic: SPK-8016 adeno-associated viral vector

Arm

Intervention/Treatment

Experimental: SPK-8016

All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8016.

Genetic: SPK-8016

adeno-associated viral vector

Outcome Measures

Primary Outcome Measures

Number of study-related adverse events, including clinically significant abnormal laboratory values. [52 weeks]
Adverse events.
Occurrence of hepatic transaminase elevation requiring immunosuppression. [52 weeks]
Number of incidences of hepatic transaminase elevation where immunosuppression is required.
Number of bleeding events (spontaneous and traumatic) after vector administration. [52 weeks]
Bleeding events.
Number of FVIII infusions after vector administration. [52 weeks]
FVIII infusions.
Peak and steady-state FVIII activity levels. [52 weeks]
Peak and steady-state FVIII activity levels assessed by coagulation clotting assays.

Secondary Outcome Measures

Vector shedding of SPK-8016 in bodily fluids. [52 weeks]
Vector shedding.
Incidence of immune response to AAV capsid protein and transgene product. [52 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Orthopaedic Institute for Children	Los Angeles	California	United States	90007
2	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
3	Illinois Bleeding and Clotting Disorders Institute	Peoria	Illinois	United States	61615
4	University of Michigan	Ann Arbor	Michigan	United States	48109
5	Mississippi Center for Advanced Medicine	Madison	Mississippi	United States	39110
6	Weill Cornell Medicine	New York	New York	United States	10065
7	Nationwide Children's	Columbus	Ohio	United States	43205
8	Oregon Health & Science University	Portland	Oregon	United States	97239
9	Penn State Health	Hershey	Pennsylvania	United States	17033
10	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
11	Jefferson University Hospitals	Philadelphia	Pennsylvania	United States	19107
12	Hemophilia Center of Western Pennsylvania	Pittsburgh	Pennsylvania	United States	15213
13	Virginia Commonwealth University School of Medicine	Richmond	Virginia	United States	23219
14	Versiti Blood Center of Wisconsin	Milwaukee	Wisconsin	United States	53226