Study of a Gene Therapy Treatment for Hemophilia A

NCT06297486 | Withdrawn Phase 3 DMC FDA Drug

• 2 other identifiers: SPK-8011-3022023-504537-46
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 27

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.

Conditions

Hemophilia A

Keywords

Dirloctocogene samoparvovec; SPK 8011; Blood coagulation factor VIII; FVIII; AAV-Spark200-BDD-hFVIII; Gene Therapy

Outcome Measures

Primary Outcomes (1)

• Annualized Bleed Rate (ABR) for All Bleeds [Cohort A]

  Up to 66 weeks post-SPK-8011 infusion

Secondary Outcomes (20)

• Median FVIII: C levels [Cohort A]

  Up to approximately 10 years

• ABR for treated bleeds [Cohort A]

  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]

  Up to approximately 10 years

• ABR for treated spontaneous, joint, and target joint bleeds [Cohort A]

  Up to approximately 10 years

• Annualized FVIII dosage [Cohort A]

  Up to approximately 10 years

Study Arms (3)

Cohort A (Primary Cohort)

EXPERIMENTAL

Participants with severe or moderately severe hemophilia A without FVIII inhibitors using routine FVIII prophylaxis

Genetic: SPK-8011

Cohort B

EXPERIMENTAL

Participants with severe or moderately severe hemophilia A without FVIII inhibitors using on-demand FVIII replacement therapy

Genetic: SPK-8011

Cohort C

EXPERIMENTAL

Participants with severe or moderately severe hemophilia A without FVIII inhibitors using emicizumab prophylaxis

Genetic: SPK-8011

Interventions

SPK-8011 GENETIC

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

Also known as: AAV-Spark200-BDD-hFVIII, Dirloctocogene samoparvovec

Cohort A (Primary Cohort); Cohort B; Cohort C

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• Have an inherited or acquired bleeding disorder other than hemophilia A
• 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.

Sponsors & Collaborators

• Spark Therapeutics, Inc.: lead

Study Sites (27)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Loma Linda University Health

Loma Linda, California, 92354, United States

Location

Orthopaedic Institute for Children/Orthopaedic Hemophilia Treatment Center

Los Angeles, California, 90007, United States

Location

Kaiser Permanente-Oakland Medical Center

Oakland, California, 94611, United States

Location

Kaiser Permanente-Roseville Medical Center

Roseville, California, 95661, United States

Location

Kaiser Permanente -Sacramento Medical Center

Sacramento, California, 95814, United States

Location

Kaiser Permanente -San Francisco Medical Center

San Francisco, California, 94115, United States

Location

University of California - San Francisco

San Francisco, California, 94143, United States

Location

Kaiser Permanente- Santa Clara Medical Center

Santa Clara, California, 94115, United States

Location

Kaiser Permanente-Vallejo Medical Center

Vallejo, California, 94589, United States

Location

Kaiser Permanente -Walnut Creek Medical Center

Walnut Creek, California, 94596, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Newark Beth Israel

Newark, New Jersey, 07112, United States

Location

Weill Cornell Medical Hospital

New York, New York, 10065, United States

Location

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

University Hospitals Cleveland

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oregon Health & Sciences University

Portland, Oregon, 97239, United States

Location

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19103, United States

Location

Cook Children's Hospital

Fort Worth, Texas, 76104, United States

Location

The University of Texas Health Science Center at Houston-Gulf States Hemophilia & Thrombosis Center

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Bloodworks NW

Seattle, Washington, 98101, United States

Location

MeSH Terms

Conditions

Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be assigned into one of three cohorts, each receiving the same study treatment.

Study Record Dates

• First Submitted: February 29, 2024
• First Posted: March 7, 2024
• Study Start: March 13, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): September 4, 2035
• Last Updated: December 13, 2024

Record last verified: 2024-12

Locations

US (27)