CompletedNCT03003533Updated Dec 30, 2024Results posted

A Gene Transfer Study for Hemophilia A

A Phase 1/2 interventional study of SPK-8011 in Hemophilia A, sponsored by Spark Therapeutics, Inc.. Completed at 16 sites in 5 countries. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-12-30.

Sponsored by Spark Therapeutics, Inc. · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 25
Allocation: Non-randomized
Ages: 18 Years and older
Sex: Male

Study 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.

Read the detailed description

Hemophilia A is a condition in which blood is unable to clot effectively. It is caused by a mutation or deletion in the gene that is responsible for producing blood-clotting factor VIII protein. Individuals with hemophilia A suffer from repeated bleeding episodes, often into the joints, which can cause chronic joint disease and sometime results in death due to the inability of the blood to clot efficiently. This chronic joint disease can have significant physical, psychosocial, and quality-of-life effects, including financial burden. The current standard of care includes the use of factor-based therapies which are given either as prophylaxis or to treat bleeding, as well as new non-factor prophylaxis therapies.

Conditions studied

Hemophilia A

Browse trials for

Hemophilia A 866

Keywords

Adeno-Associated Virus (AAV)
Blood Coagulation Disorders
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

In context

Hemophilia A

866 studies on the registry are indexed under Hemophilia A; 137 are open to participants now.

This study's enrollment of 25 is below the median of 28 across 512 interventional studies indexed under Hemophilia A.

Browse Hemophilia A studies →

Lead sponsor

Spark Therapeutics, Inc. is the lead sponsor of 14 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: Male
Accepts healthy volunteers: No

Inclusion criteria

Males age 18 years or older
Confirmed diagnosis of hemophilia A as evidenced by their medical history with baseline FVIII activity levels \<=2%
Have received >150 exposure days (EDs) to FVIII concentrates or cryoprecipitate
Have no prior history of allergic reaction to any FVIII product
Have no measurable inhibitor against FVIII as assessed by the central laboratory and have no prior history of inhibitors to FVIII protein and no clinical signs or symptoms of decreased response to FVIII administration
Agree to use reliable barrier contraception

Exclusion criteria

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 and who are on an antiretroviral drug regimen (* 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

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 25 participants (actual)

Study arms

Experimental
SPK-8011 5x10^11 vg/kg
Participants received a single intravenous (IV) infusion of SPK-8011 5x10\^11 vector genomes per kilogram (vg/kg) body weight.
Genetic: SPK-8011
Experimental
SPK-8011 1x10^12 vg/kg
Participants received a single IV infusion of SPK-8011 1x10\^12 vg/kg.
Genetic: SPK-8011
Experimental
SPK-8011 2x10^12 vg/kg
Participants received a single IV infusion of SPK-8011 2x10\^12 vg/kg.
Genetic: SPK-8011
Experimental
SPK-8011 1.5x10^12 vg/kg
Participants received a single IV infusion of SPK-8011 1.5x10\^12 vg/kg.
Genetic: SPK-8011

Interventions

GeneticSPK-8011
A novel, bio-engineered, recombinant adeno-associated viral vector carrying human factor VIII gene

What researchers measure

Primary outcomes

Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse events (SAEs) were defined as adverse events that result in death, are life-threatening, require inpatient hospitalization or prolongation of existing hospitalization, result in persistent or significant disability or incapacity, are a congenital anomaly or birth defect, or are an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A TEAE is defined as an AE with an onset date on or following SPK-8011 administration. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: From date of first dose to Week 52/End of Study (EOS) Visit
Number of Participants Who Received Corticosteroids for Presumed Immune Response
Time frame: Up to Week 52/EOS Visit
Peak Factor VIII (FVIII) Activity Levels Assessed by One-Stage Coagulation Assay (OSA)
Median peak FVIII activity up to Week 52
Time frame: Up to Week 52/EOS visit
Nominal FVIII Level by OSA at Week 52/EOS
Steady-state FVIII activity measured by median FVIII levels at week 52 by OSA.
Time frame: Up to Week 52/EOS Visit
Spontaneous Bleeds Annualized Bleeding Rate
Time frame: Week 5 up to Week 52/EOS Visit
Total Annualized FVIII Infusion Rate
Time frame: Week 5 up to Week 52/EOS Visit

Secondary outcomes

Time to Achieve Peak FVIII Activity Level
Time frame: Up to Week 52/EOS Visit
Number of Participants With Vector-shedding Confirmed Below Quantifiable Limits (BQL) of SPK-8011-101 in Bodily Fluids
Time frame: Up to Week 52/EOS Visit
Incidence of Immune Response to the BDD-hFVIII Transgene
Time frame: Up to Week 52/EOS Visit

Results

Posted Dec 30, 2024

Participant flow

Participant flow — Overall Study
Milestone	SPK-8011 5x10^11 vg/kg	SPK-8011 1x10^12 vg/kg	SPK-8011 2x10^12 vg/kg	SPK-8011 1.5x10^12 vg/kg
Started	2	3	9	11
Received at least 1 dose of study drug	2	3	9	11
Completed	2	3	9	11
Not completed	0	0	0	0

Outcome measures

PrimaryNumber of Participants With Treatment-emergent Adverse Events (TEAEs)

An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse events (SAEs) were defined as adverse events that result in death, are life-threatening, require inpatient hospitalization or prolongation of existing hospitalization, result in persistent or significant disability or incapacity, are a congenital anomaly or birth defect, or are an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A TEAE is defined as an AE with an onset date on or following SPK-8011 administration. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Time frame:: From date of first dose to Week 52/End of Study (EOS) Visit
Reported as:: Count of participants · Participants

Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Participants	SPK-8011 5x10^11 vg/kg	SPK-8011 1x10^12 vg/kg	SPK-8011 2x10^12 vg/kg	SPK-8011 1.5x10^12 vg/kg
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	2	3	9	11

PrimaryNumber of Participants Who Received Corticosteroids for Presumed Immune Response

Time frame:: Up to Week 52/EOS Visit
Reported as:: Count of participants · Participants

Number of Participants Who Received Corticosteroids for Presumed Immune Response
Participants	SPK-8011 5x10^11 vg/kg	SPK-8011 1x10^12 vg/kg	SPK-8011 2x10^12 vg/kg	SPK-8011 1.5x10^12 vg/kg
Number of Participants Who Received Corticosteroids for Presumed Immune Response	0	2	7	10

PrimaryPeak Factor VIII (FVIII) Activity Levels Assessed by One-Stage Coagulation Assay (OSA)

Median peak FVIII activity up to Week 52

Time frame:: Up to Week 52/EOS visit
Reported as:: Median · percentage of normal activity

Peak Factor VIII (FVIII) Activity Levels Assessed by One-Stage Coagulation Assay (OSA)
percentage of normal activity	SPK-8011 5x10^11 vg/kg	SPK-8011 1x10^12 vg/kg	SPK-8011 2x10^12 vg/kg	SPK-8011 1.5x10^12 vg/kg
Peak Factor VIII (FVIII) Activity Levels Assessed by One-Stage Coagulation Assay (OSA)	11.5 (11 to 12)	20.0 (6 to 24)	38.7 (7 to 209)	55.1 (31 to 112)

PrimaryNominal FVIII Level by OSA at Week 52/EOS

Steady-state FVIII activity measured by median FVIII levels at week 52 by OSA.

Time frame:: Up to Week 52/EOS Visit
Reported as:: Median · percentage of normal activity

Nominal FVIII Level by OSA at Week 52/EOS
percentage of normal activity	SPK-8011 5x10^11 vg/kg	SPK-8011 1x10^12 vg/kg	SPK-8011 2x10^12 vg/kg	SPK-8011 1.5x10^12 vg/kg
Nominal FVIII Level by OSA at Week 52/EOS	5.4 (4.7 to 6.1)	7.8 (3.0 to 13.9)	8.4 (3.0 to 19.7)	4.1 (3.0 to 11.9)

PrimarySpontaneous Bleeds Annualized Bleeding Rate

Time frame:: Week 5 up to Week 52/EOS Visit
Reported as:: Median · annualized number of bleeding events

Spontaneous Bleeds Annualized Bleeding Rate
annualized number of bleeding events	SPK-8011 5x10^11 vg/kg	SPK-8011 1x10^12 vg/kg	SPK-8011 2x10^12 vg/kg	SPK-8011 1.5x10^12 vg/kg
Spontaneous Bleeds Annualized Bleeding Rate	NA (NA to NA)	0.3 (0.2 to 0.6)	0.0 (0.0 to 1.4)	0.0 (0.0 to 0.7)

PrimaryTotal Annualized FVIII Infusion Rate

Time frame:: Week 5 up to Week 52/EOS Visit
Reported as:: Mean · total annualized FVIII infusions

Total Annualized FVIII Infusion Rate
total annualized FVIII infusions	SPK-8011 5x10^11 vg/kg	SPK-8011 1x10^12 vg/kg	SPK-8011 2x10^12 vg/kg	SPK-8011 1.5x10^12 vg/kg
Total Annualized FVIII Infusion Rate	0.3 ± 0.40	3.6 ± 3.18	7.4 ± 7.93	1.6 ± 1.81

SecondaryTime to Achieve Peak FVIII Activity Level

Time frame:: Up to Week 52/EOS Visit
Reported as:: Mean · days

Time to Achieve Peak FVIII Activity Level
days	SPK-8011 5x10^11 vg/kg	SPK-8011 1x10^12 vg/kg	SPK-8011 2x10^12 vg/kg	SPK-8011 1.5x10^12 vg/kg
Time to Achieve Peak FVIII Activity Level	279.5 ± 58.69	141.0 ± 151.79	56.4 ± 19.84	54.6 ± 33.74

SecondaryNumber of Participants With Vector-shedding Confirmed Below Quantifiable Limits (BQL) of SPK-8011-101 in Bodily Fluids

Time frame:: Up to Week 52/EOS Visit
Reported as:: Count of participants · Participants

Number of Participants With Vector-shedding Confirmed Below Quantifiable Limits (BQL) of SPK-8011-101 in Bodily Fluids
Participants	SPK-8011 5x10^11 vg/kg	SPK-8011 1x10^12 vg/kg	SPK-8011 2x10^12 vg/kg	SPK-8011 1.5x10^12 vg/kg
Peripheral blood mononuclear cells (PBMCs)	2	3	9	11
Saliva	2	3	9	10
Semen	2	2	8	11
Serum	2	3	8	10
Urine	2	3	9	10

SecondaryIncidence of Immune Response to the BDD-hFVIII Transgene

Time frame:: Up to Week 52/EOS Visit
Reported as:: Count of participants · Participants

Incidence of Immune Response to the BDD-hFVIII Transgene
Participants	SPK-8011 5x10^11 vg/kg	SPK-8011 1x10^12 vg/kg	SPK-8011 2x10^12 vg/kg	SPK-8011 1.5x10^12 vg/kg
Incidence of Immune Response to the BDD-hFVIII Transgene	0	0	0	0

Adverse events

Collected over From date of first dose up to Week 52. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
SPK-8011 5x10^11 vg/kg	0/2 (0%)	0/2 (0%)	2/2 (100%)
SPK-8011 1x10^12 vg/kg	0/3 (0%)	1/3 (33.3%)	3/3 (100%)
SPK-8011 2x10^12 vg/kg	0/9 (0%)	1/9 (11.1%)	9/9 (100%)
SPK-8011 1.5x10^12 vg/kg	0/11 (0%)	3/11 (27.3%)	11/11 (100%)

Most frequent serious events

Most frequent serious events
Event	SPK-8011 5x10^11 vg/kg	SPK-8011 1x10^12 vg/kg	SPK-8011 2x10^12 vg/kg	SPK-8011 1.5x10^12 vg/kg
AppendicitisInfections and infestations	0/2	1/3	0/9	0/11
Transaminases IncreasedInvestigations	0/2	0/3	1/9	0/11
Abdominal Pain UpperGastrointestinal disorders	0/2	0/3	0/9	1/11
HypersensitivityImmune system disorders	0/2	0/3	0/9	1/11
RhabdomyolysisMusculoskeletal and connective tissue disorders	0/2	0/3	0/9	1/11

Most frequent other events

Showing 10 of 128

Most frequent other events
Event	SPK-8011 5x10^11 vg/kg	SPK-8011 1x10^12 vg/kg	SPK-8011 2x10^12 vg/kg	SPK-8011 1.5x10^12 vg/kg
Normocytic AnaemiaBlood and lymphatic system disorders	1/2	0/3	0/9	0/11
ConjunctivitisInfections and infestations	1/2	0/3	0/9	1/11
Pulpitis DentalInfections and infestations	1/2	0/3	0/9	0/11
Iron DeficiencyMetabolism and nutrition disorders	1/2	0/3	0/9	0/11
Alanine Aminotransferase IncreasedInvestigations	0/2	0/3	1/9	5/11
Transaminases IncreasedInvestigations	0/2	0/3	2/9	5/11
ConstipationGastrointestinal disorders	0/2	0/3	0/9	4/11
Upper Respiratory Tract InfectionInfections and infestations	0/2	0/3	1/9	4/11
HeadacheNervous system disorders	0/2	0/3	1/9	4/11
InsomniaPsychiatric disorders	0/2	0/3	2/9	4/11

Baseline characteristics

The Full Analysis Set included all participants who received the infusion of SPK-8011.

Age, Categorical
Age, Categorical(Participants)	SPK-8011 5x10^11 vg/kg	SPK-8011 1x10^12 vg/kg	SPK-8011 2x10^12 vg/kg	SPK-8011 1.5x10^12 vg/kg	Total
<=18 years	0	0	0	0	0
Between 18 and 65 years	2	3	9	11	25
>=65 years	0	0	0	0	0

Sex: Female, Male
Sex: Female, Male(Participants)	SPK-8011 5x10^11 vg/kg	SPK-8011 1x10^12 vg/kg	SPK-8011 2x10^12 vg/kg	SPK-8011 1.5x10^12 vg/kg	Total
Female	0	0	0	0	0
Male	2	3	9	11	25

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	SPK-8011 5x10^11 vg/kg	SPK-8011 1x10^12 vg/kg	SPK-8011 2x10^12 vg/kg	SPK-8011 1.5x10^12 vg/kg	Total
Hispanic or Latino	0	0	0	0	0
Not Hispanic or Latino	2	3	9	11	25
Unknown or Not Reported	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	SPK-8011 5x10^11 vg/kg	SPK-8011 1x10^12 vg/kg	SPK-8011 2x10^12 vg/kg	SPK-8011 1.5x10^12 vg/kg	Total
American Indian or Alaska Native	0	0	0	0	0
Asian	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	0	1	0	1	2
White	2	2	9	10	23
More than one race	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0

Study locations

16 sites

University of California Davis - Hemostasis and Thrombosis Center
Sacramento, California 94817, United States
University of Florida Health
Gainesville, Florida 32610, United States
Boston Children's Hospital
Boston, Massachusetts 02115, United States
Mississippi Center for Advanced Medicine
Madison, Mississippi 39110, United States
Weill Cornell Medicine-Comprehensive Center for Hemophilia and Coagulation Disorders
New York, New York 10065, United States
Oregon Health & Science University
Portland, Oregon 97239, United States
Pennsylvania State University Milton S. Hershey Medical Center
Hershey, Pennsylvania 10733, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania 19104, United States
Jefferson University Hospitals
Philadelphia, Pennsylvania 19107, United States
Hemophilia Center of Western Pennsylvania
Pittsburgh, Pennsylvania 15213, United States
Virginia Commonwealth University School of Medicine
Richmond, Virginia 23219, United States
Royal Prince Alfred Hosptial
Camperdown, New South Wales 2050, Australia
The Alfred Hospital
Melbourne, 3004, Australia
McMaster University Medical Centre and Juravinski Hospital
Hamilton, Ontario L8N 3Z5, Canada
Chaim Sheba Center
Ramat Gan, Tel Hashomer 526000, Israel
Mahidol University - Ramathibody Hospital
Bangkok, 10400, Thailand

References and documents

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. PubMed 34788507 ↗
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. PubMed 32258217 ↗

Study documents

Study protocol · Feb 9, 2021
Statistical analysis plan · Mar 8, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 30, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03003533
Lead sponsor: Spark Therapeutics, Inc.
Responsible party: Sponsor
First posted: Dec 28, 2016
Start date: Jan 26, 2017
Primary completion: Dec 5, 2023
Completion: Dec 5, 2023
Results posted: Dec 30, 2024
Last update: Dec 30, 2024

Study contacts

Clinical Trial Director

study director · Spark Therapeutics, Inc.

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Dec 2024. You cannot join it, but the record below documents what was studied.

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