Adeno-Associated Virus (AAV)Phase 1/2NCT03734588

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

A Phase 1/2 study testing SPK-8016 in people with Adeno-Associated Virus (AAV) and Blood Coagulation Disorder, run by Spark Therapeutics, Inc. at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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 to evaluate the safety, efficacy, and tolerability of SPK-8016 in adult males with severe hemophilia A and no measurable inhibitor against FVIII. Read more about this study

Who is it for?: Ages 18 years and older, men only
Conditions the study is for: Adeno-Associated Virus (AAV), Blood Coagulation Disorder, Blood Coagulation Disorders, Inherited
What is being tested?: SPK-8016
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 4 participants
Where: 11 sitesUnited States
Study dates: 30 Jan 2019to 19 Jan 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

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

Show all 9Show fewer

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.

Who cannot join

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.

Trial locations and contacts

11 sites in 1 country.

City, postcode or hospital

11 sites in 1 country

United States11 sites

University of Michigan
Ann Arbor, Michigan, 48109
Penn State Health
Hershey, Pennsylvania, 17033
Orthopaedic Institute for Children
Los Angeles, California, 90007
Mississippi Center for Advanced Medicine
Madison, Mississippi, 39110
Weill Cornell Medicine
New York, New York, 10065
Illinois Bleeding and Clotting Disorders Institute
Peoria, Illinois, 61615
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

Other trials in United States

About this study

Conditions: Adeno-Associated Virus (AAV), Blood Coagulation Disorder, Blood Coagulation Disorders, Inherited, Coagulation Protein Disorders, Factor VIII (FVIII), Factor VIII (FVIII) Deficiency
Being tested: SPK-8016
Medical subject headings: Blood Coagulation Disorders, Blood Coagulation Disorders, Inherited, Coagulation Protein Disorders, Hemophilia A, 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-8016Genetic
adeno-associated viral vector

Study groups in NCT03734588
Study group	Role	What they receive
SPK-8016	Experimental	All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8016. Receives: Genetic: SPK-8016

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Measured: Up to week 52
Number of Participants With Hepatic Transaminase Elevation Requiring Immunosuppression.
Measured: Up to week 52
Peak FVIII Activity Levels Assessed by Coagulation Clotting Assays
Measured: Up to week 52
Steady-state FVIII Activity Levels Assessed by Coagulation Clotting Assays
Measured: Up to week 52
Number of Bleeding Events (Spontaneous and Traumatic) Since 28 Day Post Vector Administration
Measured: From 28 days post vector administration up to week 52
Annualized Infusion Rate
Measured: From 28 days post vector administration up to week 52

Secondary outcomes (3)

Time to Achieve Steady-state FVIII Activity Levels
Measured: Up to week 52
Number of Participants With Vector-shedding of SPK-8016 in Bodily Fluids
Measured: Up to week 52
Number of Participants With Immune Responses to AAV Capsid Protein and BDD-hFVIII Transgene
Measured: Up to week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Jan 201919 Jan 2023

First posted8 Nov 2018
Study start30 Jan 2019
Primary completion14 Oct 2020
Study completion19 Jan 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.
Other trials for Adeno-Associated Virus (AAV)Studies 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 4 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03734588
Sponsor's protocol ID: SPK-8016-101
Status last verified: Feb 2024
First submitted: 6 Nov 2018
Last updated: 23 Feb 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 23 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Dose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors
ClinicalTrials.gov ID: NCT03734588
Acronym / sponsor ID: SPK-8016-101
Conditions: Adeno-Associated Virus (AAV), Blood Coagulation Disorder, Blood Coagulation Disorders, Inherited, Coagulation Protein Disorders, Factor VIII (FVIII), Factor VIII (FVIII) Deficiency
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 4 participants (actual)
Lead sponsor: Spark Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 30 Jan 2019 (actual)
Primary completion: 14 Oct 2020 (actual)
Study completion: 19 Jan 2023 (actual)
First posted: 8 Nov 2018 (actual)
Results: Posted 23 Feb 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
SPK-8016	Experimental	Genetic: SPK-8016All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8016.

Who may qualify

Ages: 18 years and older
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Be male and ≥18 years of age;
Have clinically severe hemophilia A, defined as:
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)

Key exclusion criteria (8 listed)

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

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-8016adeno-associated viral vector	Genetic	SPK-8016

Primary outcome

Number of Participants With Adverse Events (AEs)
Time frame: Up to week 52
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Number of Participants With Hepatic Transaminase Elevation Requiring Immunosuppression.
Time frame: Up to week 52
Peak FVIII Activity Levels Assessed by Coagulation Clotting Assays
Time frame: Up to week 52
Steady-state FVIII Activity Levels Assessed by Coagulation Clotting Assays
Time frame: Up to week 52
Number of Bleeding Events (Spontaneous and Traumatic) Since 28 Day Post Vector Administration
Time frame: From 28 days post vector administration up to week 52
Annualized Infusion Rate
Time frame: From 28 days post vector administration up to week 52

3 secondary outcomes

Time to Achieve Steady-state FVIII Activity Levels
Time frame: Up to week 52
Number of Participants With Vector-shedding of SPK-8016 in Bodily Fluids
Time frame: Up to week 52
Number of Participants With Immune Responses to AAV Capsid Protein and BDD-hFVIII Transgene
Time frame: Up to week 52

Results and safety

Results posted to the registry on 23 Feb 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
SPK-8016	4	4

Primary outcome: Number of Participants With Adverse Events (AEs)

Time frame: Up to week 52. Count of participants. Unit: Participants

Measure	SPK-8016 n = 4
Value	4

Population analysed: The FAS included all enrolled participants who received the infusion of SPK-8016.

Primary outcome: Number of Participants With Hepatic Transaminase Elevation Requiring Immunosuppression.

Time frame: Up to week 52. Count of participants. Unit: Participants

Measure	SPK-8016 n = 4
Value	0

Population analysed: The FAS included all enrolled participants who received the infusion of SPK-8016.

Primary outcome: Peak FVIII Activity Levels Assessed by Coagulation Clotting Assays

Time frame: Up to week 52. Number. Unit: percentage of normal activity

Measure	SPK-8016 n = 4
Value	NA

Population analysed: The FAS included all enrolled participants who received the infusion of SPK-8016.

Primary outcome: Steady-state FVIII Activity Levels Assessed by Coagulation Clotting Assays

Time frame: Up to week 52. Mean (Standard Deviation). Unit: percentage of normal activity

Measure	SPK-8016 n = 4
Value	NA (NA)

Population analysed: The FAS included all enrolled participants who received the infusion of SPK-8016.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to week 52. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
SPK-8016	2 of 4 (50%)	4 of 4 (100%)	0 of 4

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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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.

Tiffany Chang, MD study director

Spark Therapeutics, Inc.

11 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing SPK-8016 in people with Adeno-Associated Virus (AAV) and Blood Coagulation Disorder, run by Spark Therapeutics, Inc. at 11 sites in United States.

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 9 inclusion and 8 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 23 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. 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 23 Feb 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 Adverse Events (AEs) (time frame: Up to week 52). 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 NCT03734588.

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 23 Feb 2024.