Study of a Gene Therapy Treatment for Hemophilia A

Hemophilia A Clinical Trial

— KEYSTONE 1  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06297486
• Other study ID #: SPK-8011-302
• Secondary ID: 2023-504537-46
• Status: Recruiting
• Phase: Phase 3
• Start date: March 13, 2024
• Est. completion date: September 4, 2035

Study information

• Verified date: May 2024
• Source: Spark Therapeutics, Inc.
• Contact: Clinical Trial Director
• Phone: Spark Therapeutics, Inc.
• Email: clinicaltrials[@]sparktx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 85
• Est. completion date: September 4, 2035
• Est. primary completion date: May 2027
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Genetic:
• SPK-8011
Participants will receive a single dose of SPK-8011, administered by intravenous (IV) infusion, on Day 1.

Locations

Country	Name	City	State
United States	Boston Children's Hospital	Boston	Massachusetts
United States	University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	University Hospitals Cleveland	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Cook Children's Hospital	Fort Worth	Texas
United States	University of Florida	Gainesville	Florida
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	The University of Texas Health Science Center at Houston-Gulf States Hemophilia & Thrombosis Center	Houston	Texas
United States	Loma Linda University Health	Loma Linda	California
United States	Orthopaedic Institute for Children/Orthopaedic Hemophilia Treatment Center	Los Angeles	California
United States	University of Minnesota	Minneapolis	Minnesota
United States	Weill Cornell Medical Hospital	New York	New York
United States	Newark Beth Israel	Newark	New Jersey
United States	Kaiser Permanente-Oakland Medical Center	Oakland	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Oregon Health & Sciences University	Portland	Oregon
United States	Kaiser Permanente-Roseville Medical Center	Roseville	California
United States	Kaiser Permanente -Sacramento Medical Center	Sacramento	California
United States	University of Utah	Salt Lake City	Utah
United States	Kaiser Permanente -San Francisco Medical Center	San Francisco	California
United States	University of California - San Francisco	San Francisco	California
United States	Kaiser Permanente- Santa Clara Medical Center	Santa Clara	California
United States	Bloodworks NW	Seattle	Washington
United States	Kaiser Permanente-Vallejo Medical Center	Vallejo	California
United States	Kaiser Permanente -Walnut Creek Medical Center	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Spark Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

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