Hemophilia APhase 1/2NCT03003533
A Gene Transfer Study for Hemophilia A
A Phase 1/2 study testing SPK-8011 in people with Hemophilia A, run by Spark Therapeutics, Inc. at 16 sites in 5 countries.
Trial 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 more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Hemophilia A
- What is being tested?
- SPK-8011
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 16 sitesin 5 countries
- Study dates
- 26 Jan 2017to 5 Dec 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
16 sites in 5 countries.
16 sites in 5 countries
United States11 sites
Boston Children's Hospital
Boston, Massachusetts, 02115
University of Florida Health
Gainesville, Florida, 32610
Pennsylvania State University Milton S. Hershey Medical Center
Hershey, Pennsylvania, 10733
Mississippi Center for Advanced Medicine
Madison, Mississippi, 39110
Weill Cornell Medicine-Comprehensive Center for Hemophilia and Coagulation Disorders
New York, New York, 10065
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Jefferson University Hospitals
Philadelphia, Pennsylvania, 19107
Hemophilia Center of Western Pennsylvania
Pittsburgh, Pennsylvania, 15213
Oregon Health & Science University
Portland, Oregon, 97239
Virginia Commonwealth University School of Medicine
Richmond, Virginia, 23219
University of California Davis - Hemostasis and Thrombosis Center
Sacramento, California, 94817
Australia2 sites
Royal Prince Alfred Hosptial
Camperdown, New South Wales, 2050
The Alfred Hospital
Melbourne, 3004
Canada1 site
McMaster University Medical Centre and Juravinski Hospital
Hamilton, Ontario, L8N 3Z5
About this study
Official 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
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
- Hemophilia A
- Being tested
- SPK-8011
- 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
- Medical subject headings
- Hemophilia A, Blood Coagulation Disorders, Blood Coagulation Disorders, Inherited, Coagulation Protein Disorders, Genetic Diseases, Inborn, Genetic Diseases, X-Linked, Hematologic Diseases, Hemorrhagic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SPK-8011Genetic
A novel, bio-engineered, recombinant adeno-associated viral vector carrying human factor VIII gene
| Study group | Role | What they receive |
|---|---|---|
| SPK-8011 5x10^11 vg/kg | Experimental | Participants received a single intravenous (IV) infusion of SPK-8011 5x10^11 vector genomes per kilogram (vg/kg) body weight. Receives: Genetic: SPK-8011 |
| SPK-8011 1x10^12 vg/kg | Experimental | Participants received a single IV infusion of SPK-8011 1x10^12 vg/kg. Receives: Genetic: SPK-8011 |
| SPK-8011 2x10^12 vg/kg | Experimental | Participants received a single IV infusion of SPK-8011 2x10^12 vg/kg. Receives: Genetic: SPK-8011 |
| SPK-8011 1.5x10^12 vg/kg | Experimental | Participants received a single IV infusion of SPK-8011 1.5x10^12 vg/kg. Receives: Genetic: SPK-8011 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From date of first dose to Week 52/End of Study (EOS) Visit
Number of Participants Who Received Corticosteroids for Presumed Immune Response
Measured: 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
Measured: 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.
Measured: Up to Week 52/EOS Visit
Spontaneous Bleeds Annualized Bleeding Rate
Measured: Week 5 up to Week 52/EOS Visit
Total Annualized FVIII Infusion Rate
Measured: Week 5 up to Week 52/EOS Visit
Secondary outcomes (3)
Time to Achieve Peak FVIII Activity Level
Measured: Up to Week 52/EOS Visit
Number of Participants With Vector-shedding Confirmed Below Quantifiable Limits (BQL) of SPK-8011-101 in Bodily Fluids
Measured: Up to Week 52/EOS Visit
Incidence of Immune Response to the BDD-hFVIII Transgene
Measured: Up to Week 52/EOS Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2016 (estimated)
- Study start26 Jan 2017
- Primary completion5 Dec 2023
- Study completion5 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spark Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Director, Study director, Spark Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03003533
- Sponsor's protocol ID
- SPK-8011-101
- Status last verified
- Dec 2024
- First submitted
- 16 Dec 2016
- Last updated
- 30 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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 34788507Ran 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 at a glance
From the registry record, last updated by the sponsor on 30 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT03003533
- Acronym / sponsor ID
- SPK-8011-101
- Conditions
- Hemophilia A
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Spark Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 26 Jan 2017 (actual)
- Primary completion
- 5 Dec 2023 (actual)
- Study completion
- 5 Dec 2023 (actual)
- First posted
- 28 Dec 2016 (estimated)
- Results
- Posted 30 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| SPK-8011 5x10^11 vg/kg | Experimental | Genetic: SPK-8011Participants received a single intravenous (IV) infusion of SPK-8011 5x10^11 vector genomes per kilogram (vg/kg) body weight. |
| SPK-8011 1x10^12 vg/kg | Experimental | Genetic: SPK-8011Participants received a single IV infusion of SPK-8011 1x10^12 vg/kg. |
| SPK-8011 2x10^12 vg/kg | Experimental | Genetic: SPK-8011Participants received a single IV infusion of SPK-8011 2x10^12 vg/kg. |
| SPK-8011 1.5x10^12 vg/kg | Experimental | Genetic: SPK-8011Participants received a single IV infusion of SPK-8011 1.5x10^12 vg/kg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SPK-8011A novel, bio-engineered, recombinant adeno-associated viral vector carrying human factor VIII gene | Genetic | SPK-8011 1.5x10^12 vg/kg, SPK-8011 1x10^12 vg/kg, SPK-8011 2x10^12 vg/kg, SPK-8011 5x10^11 vg/kg |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: From date of first dose to Week 52/End of Study (EOS) Visit
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.
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)
Time frame: Up to Week 52/EOS visit
Median peak FVIII activity up to Week 52
Nominal FVIII Level by OSA at Week 52/EOS
Time frame: Up to Week 52/EOS Visit
Steady-state FVIII activity measured by median FVIII levels at week 52 by OSA.
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
3 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 and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34788507George 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.
- Derived from this study: PubMed 32258217Ran 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trial Director study director
Spark Therapeutics, Inc.
16 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SPK-8011 in people with Hemophilia A, run by Spark Therapeutics, Inc. at 16 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, Australia, Canada, Israel, Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: From date of first dose to Week 52/End of Study (EOS) Visit). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03003533, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2024.