History of Changes for Study: NCT03734588

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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Study Record Versions

Version	Submitted Date	Changes
1	November 7, 2018	None (earliest Version on record)
2	November 12, 2018	Study Description, Oversight and Study Status
3	December 13, 2018	Recruitment Status, Study Status and Contacts/Locations
4	March 11, 2019	Contacts/Locations, Study Status and IPDSharing
5	December 3, 2019	Study Status and Contacts/Locations
6	May 14, 2020	Recruitment Status, Study Status and Contacts/Locations
7	October 30, 2020	Study Status
8	January 15, 2021	Study Status
9	February 3, 2022	Recruitment Status, Contacts/Locations and Study Status
10	July 15, 2022	Contacts/Locations and Study Status
11	October 28, 2022	Contacts/Locations and Study Status
12	January 18, 2023	Study Status
13	February 21, 2023	Recruitment Status, Study Status, Contacts/Locations and Study Design
14	January 18, 2024	Quality Control Review has not concluded Returned: February 12, 2024 Recruitment Status, Study Status, Outcome Measures, Document Section, Eligibility and Study Description
15	February 22, 2024	Study Status, Outcome Measures and Participant Flow

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Study Identification


Unique Protocol ID:	SPK-8016-101
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
Secondary IDs:

Study Status


Record Verification:	November 2018 February 2023
Overall Status:	Not yet recruiting Active, not recruiting
Study Start:	November 2018 January 30, 2019
Primary Completion:	April 2020 March 2023 [Anticipated]
Study Completion:	April 2020 December 2023 [Anticipated]

First Submitted:	November 6, 2018
First Submitted that Met QC Criteria:	November 7, 2018
First Posted:	November 8, 2018 [Actual]

Last Update Submitted that Met QC Criteria:	November 7, 2018 February 21, 2023
Last Update Posted:	November 8, 2018 [Actual] February 22, 2023 [Actual]

Sponsor/Collaborators


Sponsor:	Spark Therapeutics, Inc.
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	Yes

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 hemopihilia 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.

Detailed Description:

Conditions


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
Keywords:

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 1/Phase 2
Interventional Study Model:	Single Group Assignment
Number of Arms:	1
Masking:	None (Open Label)
Allocation:	N/A
Enrollment:	30 [Anticipated] 4 [Actual]

Arms and Interventions

Arms	Assigned Interventions
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:
1.	Number of study-related adverse events, including clinically significant abnormal laboratory values. [ Time Frame: 52 weeks ] Adverse events.
2.	Occurrence of hepatic transaminase elevation requiring immunosuppression. [ Time Frame: 52 weeks ] Number of incidences of hepatic transaminase elevation where immunosuppression is required.
3.	Number of bleeding events (spontaneous and traumatic) after vector administration. [ Time Frame: 52 weeks ] Bleeding events.
4.	Number of FVIII infusions after vector administration. [ Time Frame: 52 weeks ] FVIII infusions.
5.	Peak and steady-state FVIII activity levels. [ Time Frame: 52 weeks ] Peak and steady-state FVIII activity levels assessed by coagulation clotting assays.
Secondary Outcome Measures:
1.	Vector shedding of SPK-8016 in bodily fluids. [ Time Frame: 52 weeks ] Vector shedding.
2.	Incidence of immune response to AAV capsid protein and transgene product. [ Time Frame: 52 weeks ]

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	Male
Gender Based:	Yes
	Genetically male
Accepts Healthy Volunteers:	No
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.

Contacts/Locations


Central Contact Person:	Clinical Director Telephone: +1 215-220-9300 Email: clinicaltrials@sparktx.com
Study Officials:	Clinical Director Tiffany Chang, MD Study Director clinicaltrials@sparktx.com Spark Therapeutics, Inc.
Locations:	United States, California
	Orthopaedic Institute for Children Los Angeles, California, United States, 90007
	United States, Illinois
	Illinois Bleeding and Clotting Disorders Institute Peoria, Illinois, United States, 61615
	United States, Michigan
	University of Michigan Ann Arbor, Michigan, United States, 48109
	United States, Mississippi
	Mississippi Center for Advanced Medicine Madison, Mississippi, United States, 39110
	United States, New York
	Weill Cornell Medicine New York, New York, United States, 10065
	United States, Oregon
	Oregon Health & Science University Portland, Oregon, United States, 97239
	United States, Pennsylvania
	Penn State Health Hershey, Pennsylvania, United States, 17033
	Children's Hospital of Philadelphia Philadelphia, Pennsylvania, United States, 19104
	Jefferson University Hospitals Philadelphia, Pennsylvania, United States, 19107
	Hemophilia Center of Western Pennsylvania Pittsburgh, Pennsylvania, United States, 15213
	United States, Virginia
	Virginia Commonwealth University School of Medicine Richmond, Virginia, United States, 23219

IPDSharing


Plan to Share IPD:	Undecided No

References


Citations:
Links:
Available IPD/Information: