Hemophilia APhase 3KEYSTONE 1NCT06297486

Study of a Gene Therapy Treatment for Hemophilia A

A Phase 3 study testing SPK-8011 in people with Hemophilia A, run by Spark Therapeutics, Inc. at 27 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

The purpose of this study is to evaluate the efficacy of SPK-8011 in preventing bleed episodes compared with FVIII prophylaxis in participants with hemophilia A without FVIII inhibitors on routine FVIII prophylaxis. 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: 0 participants
Where: 27 sitesUnited States
Study dates: 13 Mar 2024to 4 Sep 2035
Phase: Phase 3
Are there results?: None posted in the registry

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

Have a negative anti-AAV-Spark200 neutralizing antibody (NAb) test result.
Are adult males with severe or moderately severe hemophilia A, defined as endogenous FVIII activity ≤3%, as documented by a certified laboratory (historically or during the Screening Period) and where the FVIII:C level is measured more than 96 hours after the prior dose of an extended-half-life FVIII
Have ≥150 documented exposure days to an FVIII protein product such as recombinant, plasma-derived, or extended half-life FVIII product
Have no prior history of hypersensitivity or anaphylaxis associated with the administration of any FVIII product.
Have screening hepatic ultrasound without evidence of cirrhosis and no laboratory or clinical evidence per the Investigator's judgment of advanced liver disease or cirrhosis.
Have a negative test for inhibitor against FVIII (ie, <0.6 Bethesda units [BU]) during screening.

Show all 13Show fewer

Have no documented FVIII inhibitor (ie, <0.6 BU), FVIII half-life <6 hours, or FVIII recovery <66% in the 5 years prior to screening.
Candidates who completed successful immune tolerance induction (ITI) at least 5 years before screening are eligible, provided they have had no evidence of inhibitor recurrence (permanent or temporary) within 5 years prior to screening as may be indicated by detection of an inhibitor, FVIII half-life <6 hours, or FVIII recovery <66% since completing ITI.
If human immunodeficiency virus (HIV)-positive at screening, have an adequate cluster of differentiation 4 (CD4) count (>200/mm3) and undetectable viral load (<50 genome copies [gc]/mL), are on an antiretroviral drug regimen, and have completed at least 12 weeks of this treatment regimen prior to screening.
Meet the following inclusion criteria by cohort:
Cohort A: have documented history of prior treatment with FVIII prophylaxis (defined as receiving a prescribed dose and frequency of FVIII infusions with the intent to treat continuously for 52 weeks per year) for a minimum of 6 months prior to screening; and are willing to continue their FVIII prophylaxis during the Lead-In Period of this study (minimum of 24 weeks).
Cohort B: have documented history of prior treatment with FVIII on demand for a minimum of 6 months that shows ≥5 treated bleeds in the last 6 months prior to screening.
Cohort C: have documented history of prior treatment with emicizumab prophylaxis for a minimum of 6 months prior to screening.

Who cannot join

Have an inherited or acquired bleeding disorder other than hemophilia A
Have inherited or acquired thrombophilia, have signs of thromboembolic disease in the Investigator's judgment, or are on current treatment for thromboembolic disease. A history of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing is not considered an exclusion criterion.
Have concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study or that would, in the opinion of the Investigator or Sponsor, preclude the candidate's safe participation in and completion of the study, or the interpretation of the study results.

Trial locations and contacts

27 sites in 1 country.

City, postcode or hospital

27 sites in 1 country

United States27 sites

Boston Children's Hospital
Boston, Massachusetts, 02115
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27514
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
University Hospitals Cleveland
Cleveland, Ohio, 44106
Nationwide Children's Hospital
Columbus, Ohio, 43205
Cook Children's Hospital
Fort Worth, Texas, 76104
University of Florida
Gainesville, Florida, 32610
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033
The University of Texas Health Science Center at Houston-Gulf States Hemophilia & Thrombosis Center
Houston, Texas, 77030
Loma Linda University Health
Loma Linda, California, 92354
Orthopaedic Institute for Children/Orthopaedic Hemophilia Treatment Center
Los Angeles, California, 90007
University of Minnesota
Minneapolis, Minnesota, 55455
Weill Cornell Medical Hospital
New York, New York, 10065
Newark Beth Israel
Newark, New Jersey, 07112
Kaiser Permanente-Oakland Medical Center
Oakland, California, 94611
University of Pennsylvania
Philadelphia, Pennsylvania, 19103
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Oregon Health & Sciences University
Portland, Oregon, 97239
Kaiser Permanente-Roseville Medical Center
Roseville, California, 95661
Kaiser Permanente -Sacramento Medical Center
Sacramento, California, 95814
University of Utah
Salt Lake City, Utah, 84112
Kaiser Permanente -San Francisco Medical Center
San Francisco, California, 94115
University of California - San Francisco
San Francisco, California, 94143
Kaiser Permanente- Santa Clara Medical Center
Santa Clara, California, 94115
Bloodworks NW
Seattle, Washington, 98101
Kaiser Permanente-Vallejo Medical Center
Vallejo, California, 94589
Kaiser Permanente -Walnut Creek Medical Center
Walnut Creek, California, 94596

Other trials in United States

About this study

Official title: A Phase 3, Single-arm, Open-label, Multicenter Study of the Safety and Efficacy of Dirloctocogene Samoparvovec (SPK 8011, Adeno-associated Viral Vector With B-domain Deleted Human Factor VIII Gene) in Adults With Severe or Moderately Severe Hemophilia A

Conditions: Hemophilia A
Being tested: SPK-8011
Keywords: Dirloctocogene samoparvovec, SPK 8011, Blood coagulation factor VIII, FVIII, AAV-Spark200-BDD-hFVIII, Gene Therapy
Medical subject headings: Hemophilia A

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SPK-8011Genetic
Also called AAV-Spark200-BDD-hFVIII, Dirloctocogene samoparvovec
Participants will receive a single dose of SPK-8011, administered by intravenous (IV) infusion, on Day 1.

Study groups in NCT06297486
Study group	Role	What they receive
Cohort A (Primary Cohort)	Experimental	Participants with severe or moderately severe hemophilia A without FVIII inhibitors using routine FVIII prophylaxis Receives: Genetic: SPK-8011
Cohort B	Experimental	Participants with severe or moderately severe hemophilia A without FVIII inhibitors using on-demand FVIII replacement therapy Receives: Genetic: SPK-8011
Cohort C	Experimental	Participants with severe or moderately severe hemophilia A without FVIII inhibitors using emicizumab prophylaxis Receives: Genetic: SPK-8011

What is being measured

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

Annualized Bleed Rate (ABR) for All Bleeds [Cohort A]
Measured: Up to 66 weeks post-SPK-8011 infusion

Secondary outcomes (20)

Median FVIII: C levels [Cohort A]
Measured: Up to approximately 10 years
ABR for treated bleeds [Cohort A]
Measured: Up to approximately 10 years
Percentage of Participants with ABR=0 for all bleeds; treated bleeds; treated spontaneous bleeds; and treated joint and target joint bleeds [Cohort A]
Measured: Up to approximately 10 years
ABR for treated spontaneous, joint, and target joint bleeds [Cohort A]
Measured: Up to approximately 10 years
Annualized FVIII dosage [Cohort A]
Measured: Up to approximately 10 years
Proportion of Resolved Target Joints [Cohort A]
Measured: Up to approximately 10 years
Mean Change of Total Hemophilia Joint Health Score [Cohort A]
Measured: Baseline, up to 66 weeks post-SPK-8011 infusion
FVIII:C levels over time [Cohort A]
Measured: Up to approximately 10 years
Mean ABR for all bleeds and treated bleeds [Cohort C]
Measured: Up to approximately 10 years
FVIII: C levels over time from Week 26 [Cohort C]
Measured: Up to approximately 10 years
Proportion of Participants Who Receive IV Methylprednisolone (IVMP) Prior to Week 8 (Early IVMP) [Cohorts A, B, C]
Measured: Up to approximately 10 years
Proportion of Participants Who Receive Secondary Oral Immunomodulation [Cohorts A, B, C]
Measured: Up to approximately 10 years
Median Time to First Immunomodulation-related Corticosteroid Dose [Cohorts A, B, C]
Measured: Up to approximately 10 years
Median Duration of Secondary Oral Immunomodulation [Cohorts A, B, C]
Measured: Up to approximately 10 years
Proportion of Participants with FVIII Inhibitor Development [Cohorts A, B, C]
Measured: Up to approximately 10 years
Proportion of participants with Treatment-related AEs of ALT Elevation [Cohorts A, B, C]
Measured: Up to approximately 10 years
Proportion of participants with treatment-related AEs of Infusion Reaction [Cohorts A, B, C]
Measured: Up to approximately 10 years
Number of participants with abnormal physical exam findings, abnormal vital signs, and abnormal selected clinical laboratory test results [Cohorts A, B, C]
Measured: Up to approximately 10 years
Proportion of participants with AEs and SAEs [Cohorts A, B, C]
Measured: Up to approximately 10 years
Proportion of participants with AESIs [Cohorts A, B, C]
Measured: Up to approximately 10 years

Timeline

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

13 Mar 20244 Sep 2035

First posted7 Mar 2024
Study start13 Mar 2024
Primary completionMay 2027 (estimated)
Study completion4 Sep 2035 (estimated)

Why it stopped: Strategic Decision

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
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 3
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Model description: Participants will be assigned into one of three cohorts, each receiving the same study treatment.
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06297486
Sponsor's protocol ID: SPK-8011-302
Other IDs: 2023-504537-46, 2023
Acronym: KEYSTONE 1
Status last verified: Dec 2024
First submitted: 29 Feb 2024
Last updated: 13 Dec 2024
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: 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

RecruitingObservational study
The CACHE Study: Coronary Artery Care in HaEmophilia
Haemophilia, Cardiovascular Diseases
Active, not recruitingObservational study
A Study to Learn About the Study Medicine -Hympavzi in Congenital Hemophilia Patients Without Inhibitors in Japan.
Hemophilia A or B
RecruitingPhase 1/2
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
Hemophilia A
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
Hemophilia B
Not yet recruiting
Safety of Intraosseous Anaesthesia in Children With Haemophilia
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All Hemophilia A trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3, Single-arm, Open-label, Multicenter Study of the Safety and Efficacy of Dirloctocogene Samoparvovec (SPK 8011, Adeno-associated Viral Vector With B-domain Deleted Human Factor VIII Gene) in Adults With Severe or Moderately Severe Hemophilia A
ClinicalTrials.gov ID: NCT06297486
Acronym / sponsor ID: KEYSTONE 1 / SPK-8011-302
Conditions: Hemophilia A
Keywords: Dirloctocogene samoparvovec, SPK 8011, Blood coagulation factor VIII, FVIII, AAV-Spark200-BDD-hFVIII, Gene Therapy
Phase: Phase 3
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Strategic Decision
Enrolment: 0 participants (actual)
Lead sponsor: Spark Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 13 Mar 2024 (actual)
Primary completion: May 2027 (estimated)
Study completion: 4 Sep 2035 (estimated)
First posted: 7 Mar 2024 (actual)
Results: Not posted in the source record

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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3
Model description: Participants will be assigned into one of three cohorts, each receiving the same study treatment.

Arm	Type	Receives
Cohort A (Primary Cohort)	Experimental	Genetic: SPK-8011Participants with severe or moderately severe hemophilia A without FVIII inhibitors using routine FVIII prophylaxis
Cohort B	Experimental	Genetic: SPK-8011Participants with severe or moderately severe hemophilia A without FVIII inhibitors using on-demand FVIII replacement therapy
Cohort C	Experimental	Genetic: SPK-8011Participants with severe or moderately severe hemophilia A without FVIII inhibitors using emicizumab prophylaxis

Who may qualify

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

Key inclusion criteria (13 listed)

Have a negative anti-AAV-Spark200 neutralizing antibody (NAb) test result.
Are adult males with severe or moderately severe hemophilia A, defined as endogenous FVIII activity ≤3%, as documented by a certified laboratory (historically or during the Screening Period) and where the FVIII:C level is measured more than 96 hours after the prior dose of an extended-half-life FVIII
Have ≥150 documented exposure days to an FVIII protein product such as recombinant, plasma-derived, or extended half-life FVIII product
Have no prior history of hypersensitivity or anaphylaxis associated with the administration of any FVIII product.
Have screening hepatic ultrasound without evidence of cirrhosis and no laboratory or clinical evidence per the Investigator's judgment of advanced liver disease or cirrhosis.

Key exclusion criteria (3 listed)

Have an inherited or acquired bleeding disorder other than hemophilia A
Have inherited or acquired thrombophilia, have signs of thromboembolic disease in the Investigator's judgment, or are on current treatment for thromboembolic disease. A history of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing is not considered an exclusion criterion.
Have concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study or that would, in the opinion of the Investigator or Sponsor, preclude the candidate's safe participation in and completion of the study, or the interpretation of the study results.

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-8011Also: AAV-Spark200-BDD-hFVIII, Dirloctocogene samoparvovecParticipants will receive a single dose of SPK-8011, administered by intravenous (IV) infusion, on Day 1.	Genetic	Cohort A (Primary Cohort), Cohort B, Cohort C

Primary outcome

Annualized Bleed Rate (ABR) for All Bleeds [Cohort A]
Time frame: Up to 66 weeks post-SPK-8011 infusion

20 secondary outcomes

Median FVIII: C levels [Cohort A]
Time frame: Up to approximately 10 years
ABR for treated bleeds [Cohort A]
Time frame: Up to approximately 10 years
Percentage of Participants with ABR=0 for all bleeds; treated bleeds; treated spontaneous bleeds; and treated joint and target joint bleeds [Cohort A]
Time frame: Up to approximately 10 years
ABR for treated spontaneous, joint, and target joint bleeds [Cohort A]
Time frame: Up to approximately 10 years
Annualized FVIII dosage [Cohort A]
Time frame: Up to approximately 10 years
Proportion of Resolved Target Joints [Cohort A]
Time frame: Up to approximately 10 years
Mean Change of Total Hemophilia Joint Health Score [Cohort A]
Time frame: Baseline, up to 66 weeks post-SPK-8011 infusion
FVIII:C levels over time [Cohort A]
Time frame: Up to approximately 10 years
Mean ABR for all bleeds and treated bleeds [Cohort C]
Time frame: Up to approximately 10 years
FVIII: C levels over time from Week 26 [Cohort C]
Time frame: Up to approximately 10 years
Proportion of Participants Who Receive IV Methylprednisolone (IVMP) Prior to Week 8 (Early IVMP) [Cohorts A, B, C]
Time frame: Up to approximately 10 years
Proportion of Participants Who Receive Secondary Oral Immunomodulation [Cohorts A, B, C]
Time frame: Up to approximately 10 years
Median Time to First Immunomodulation-related Corticosteroid Dose [Cohorts A, B, C]
Time frame: Up to approximately 10 years
Median Duration of Secondary Oral Immunomodulation [Cohorts A, B, C]
Time frame: Up to approximately 10 years
Proportion of Participants with FVIII Inhibitor Development [Cohorts A, B, C]
Time frame: Up to approximately 10 years
Proportion of participants with Treatment-related AEs of ALT Elevation [Cohorts A, B, C]
Time frame: Up to approximately 10 years
Proportion of participants with treatment-related AEs of Infusion Reaction [Cohorts A, B, C]
Time frame: Up to approximately 10 years
Number of participants with abnormal physical exam findings, abnormal vital signs, and abnormal selected clinical laboratory test results [Cohorts A, B, C]
Time frame: Up to approximately 10 years
Proportion of participants with AEs and SAEs [Cohorts A, B, C]
Time frame: Up to approximately 10 years
Proportion of participants with AESIs [Cohorts A, B, C]
Time frame: Up to approximately 10 years

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2024.

Related trials for Hemophilia A

RecruitingObservational study
The CACHE Study: Coronary Artery Care in HaEmophilia
Haemophilia, Cardiovascular Diseases
Active, not recruitingObservational study
A Study to Learn About the Study Medicine -Hympavzi in Congenital Hemophilia Patients Without Inhibitors in Japan.
Hemophilia A or B
RecruitingPhase 1/2
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
Hemophilia A
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
Hemophilia B
Not yet recruiting
Safety of Intraosseous Anaesthesia in Children With Haemophilia
Haemophilia A, Haemophilia B

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.

The record lists no contact. Use the official record to reach the sponsor.

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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing SPK-8011 in people with Hemophilia A, run by Spark Therapeutics, Inc. at 27 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 13 inclusion and 3 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: withdrawn, as of the sponsor's last update on 13 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 27 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 phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Annualized Bleed Rate (ABR) for All Bleeds [Cohort A] (time frame: Up to 66 weeks post-SPK-8011 infusion). 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 NCT06297486.

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 13 Dec 2024.