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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03003533




Registration number
NCT03003533
Ethics application status
Date submitted
16/12/2016
Date registered
28/12/2016
Date last updated
9/01/2024

Titles & IDs
Public title
A Gene Transfer Study for Hemophilia A
Scientific title
Gene-transfer, Open-label, Dose-escalation Study of SPK-8011 [Adeno-associated Viral Vector With B-domain Deleted Human Factor VIII Gene] in Individuals With Hemophilia A
Secondary ID [1] 0 0
SPK-8011-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia A 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - SPK-8011

Experimental: SPK-8011 - All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8011.


Treatment: Other: SPK-8011
A novel, bio-engineered, recombinant adeno-associated viral vector carrying human factor VIII gene
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of study-related adverse events, including clinically significant abnormal laboratory values
Timepoint [1] 0 0
52 weeks
Primary outcome [2] 0 0
Changes from baseline in FVIII activity levels after a single outpatient administration of SPK-8011
Timepoint [2] 0 0
52 weeks
Secondary outcome [1] 0 0
Kinetic assessment of SPK-8011 including shedding of vector DNA in bodily fluids
Timepoint [1] 0 0
52 weeks
Secondary outcome [2] 0 0
Number of participants requiring a course of steroid therapy for the elevations in liver enzymes
Timepoint [2] 0 0
52 weeks

Eligibility
Key inclusion criteria
* Males age18 years or older
* Confirmed diagnosis of hemophilia A as evidenced by their medical history with plasma FVIII activity levels = 2% of normal
* Have received >150 exposure days (EDs) to FVIII concentrates or cryoprecipitate
* Have experienced >10 bleeding events over the previous 12 months only if receiving on-demand therapy and having FVIII baseline level 1-2% of normal
* Have no prior history of allergic reaction to any FVIII product
* Have no measurable inhibitor against Factor VIII as assessed by the central laboratory and have no prior history of inhibitors to FVIII protein
* Agree to use reliable barrier contraception
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Evidence of active hepatitis B or C
* Currently on antiviral therapy for 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+ and stable with CD4 count >200/mm3 and undetectable viral load are eligible to enroll)
* Have detectable antibodies reactive with AAV-Spark200 capsid
* Participated in a gene transfer trial within the last 52 weeks or in a clinical trial with an investigational product within the last 12 weeks

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/01/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/12/2023
Sample size
Target
Accrual to date
Final
25
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Royal Prince Alfred Hosptial - Camperdown
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Mississippi
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Oregon
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Israel
State/province [10] 0 0
Tel Hashomer
Country [11] 0 0
Thailand
State/province [11] 0 0
Bangkok

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Spark Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This clinical research study is being conducted by Spark Therapeutics, Inc. to determine the safety and efficacy of the factor VIII gene transfer treatment with SPK-8011 in individuals with hemophilia A.
Trial website
https://clinicaltrials.gov/study/NCT03003533
Trial related presentations / publications
George LA, Monahan PE, Eyster ME, Sullivan SK, Ragni MV, Croteau SE, Rasko JEJ, Recht M, Samelson-Jones BJ, MacDougall A, Jaworski K, Noble R, Curran M, Kuranda K, Mingozzi F, Chang T, Reape KZ, Anguela XM, High KA. Multiyear Factor VIII Expression after AAV Gene Transfer for Hemophilia A. N Engl J Med. 2021 Nov 18;385(21):1961-1973. doi: 10.1056/NEJMoa2104205.
Ran G, Chen X, Xie Y, Zheng Q, Xie J, Yu C, Pittman N, Qi S, Yu FX, Agbandje-McKenna M, Srivastava A, Ling C. Site-Directed Mutagenesis Improves the Transduction Efficiency of Capsid Library-Derived Recombinant AAV Vectors. Mol Ther Methods Clin Dev. 2020 Mar 13;17:545-555. doi: 10.1016/j.omtm.2020.03.007. eCollection 2020 Jun 12.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trial Director
Address 0 0
Spark Therapeutics, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03003533