Clinical trial NCT06297486: Study of a Gene Therapy Treatment for Hemophilia A
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Hemophilia A
Keywords: Dirloctocogene samoparvovec
SPK 8011
Blood coagulation factor VIII
FVIII
AAV-Spark200-BDD-hFVIII
Gene Therapy
Lead sponsor: Spark Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-03-07
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be assigned into one of three cohorts, each receiving the same study treatment.
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Annualized Bleed Rate (ABR) for All Bleeds [Cohort A]
timeFrame: Up to 66 weeks post-SPK-8011 infusion
Secondary outcomes:
measure: Median FVIII: C levels [Cohort A]
timeFrame: Up to approximately 10 years
measure: ABR for treated bleeds [Cohort A]
timeFrame: Up to approximately 10 years
measure: Percentage of Participants with ABR=0 for all bleeds; treated bleeds; treated spontaneous bleeds; and treated joint and target joint bleeds [Cohort A]
timeFrame: Up to approximately 10 years
measure: ABR for treated spontaneous, joint, and target joint bleeds [Cohort A]
timeFrame: Up to approximately 10 years
measure: Annualized FVIII dosage [Cohort A]
timeFrame: Up to approximately 10 years
measure: Proportion of Resolved Target Joints [Cohort A]
timeFrame: Up to approximately 10 years
measure: Mean Change of Total Hemophilia Joint Health Score [Cohort A]
timeFrame: Baseline, up to 66 weeks post-SPK-8011 infusion
measure: FVIII:C levels over time [Cohort A]
timeFrame: Up to approximately 10 years
measure: Mean ABR for all bleeds and treated bleeds [Cohort C]
timeFrame: Up to approximately 10 years
measure: FVIII: C levels over time from Week 26 [Cohort C]
timeFrame: Up to approximately 10 years
measure: Proportion of Participants Who Receive IV Methylprednisolone (IVMP) Prior to Week 8 (Early IVMP) [Cohorts A, B, C]
timeFrame: Up to approximately 10 years
measure: Proportion of Participants Who Receive Secondary Oral Immunomodulation [Cohorts A, B, C]
timeFrame: Up to approximately 10 years
measure: Median Time to First Immunomodulation-related Corticosteroid Dose [Cohorts A, B, C]
timeFrame: Up to approximately 10 years
measure: Median Duration of Secondary Oral Immunomodulation [Cohorts A, B, C]
timeFrame: Up to approximately 10 years
measure: Proportion of Participants with FVIII Inhibitor Development [Cohorts A, B, C]
timeFrame: Up to approximately 10 years
measure: Proportion of participants with Treatment-related AEs of ALT Elevation [Cohorts A, B, C]
timeFrame: Up to approximately 10 years
measure: Proportion of participants with treatment-related AEs of Infusion Reaction [Cohorts A, B, C]
timeFrame: Up to approximately 10 years
measure: Number of participants with abnormal physical exam findings, abnormal vital signs, and abnormal selected clinical laboratory test results [Cohorts A, B, C]
timeFrame: Up to approximately 10 years
measure: Proportion of participants with AEs and SAEs [Cohorts A, B, C]
timeFrame: Up to approximately 10 years
measure: Proportion of participants with AESIs [Cohorts A, B, C]
timeFrame: Up to approximately 10 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University Health
state: California
city: Los Angeles
country: United States
facility: Orthopaedic Institute for Children/Orthopaedic Hemophilia Treatment Center
state: California
city: Oakland
country: United States
facility: Kaiser Permanente-Oakland Medical Center
state: California
city: Roseville
country: United States
facility: Kaiser Permanente-Roseville Medical Center
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente -Sacramento Medical Center
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente -San Francisco Medical Center
state: California
city: San Francisco
country: United States
facility: University of California - San Francisco
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente- Santa Clara Medical Center
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente-Vallejo Medical Center
state: California
city: Walnut Creek
country: United States
facility: Kaiser Permanente -Walnut Creek Medical Center
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Newark
country: United States
facility: Newark Beth Israel
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medical Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina - Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Sciences University
state: Oregon
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Fort Worth
country: United States
facility: Cook Children's Hospital
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston-Gulf States Hemophilia & Thrombosis Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Bloodworks NW
state: Washington
Study officials:
References: