Long-Term Safety and Efficacy of Spark-Sponsored Gene Therapies in Males With Hemophilia A

• ClinicalTrials.gov Identifier: NCT03432520
• Recruitment Status: Enrolling by invitation
• First Posted: February 14, 2018
• Last Update Posted: February 10, 2022
• Sponsor: Spark Therapeutics
• Information provided by (Responsible Party): Spark Therapeutics

Study Description

Brief Summary:

This long-term follow-up study will continue to evaluate the long-term safety and efficacy of SPK-8011 and SPK-8016 in males with hemophilia A, who have received a single intravenous administration of SPK-8011 or SPK-8016 in any Spark-sponsored SPK-8011 or SPK-8016 study.

Condition or disease	Intervention/treatment
Hemophilia A	Genetic: SPK-8011

Detailed Description:

This study will follow patients with hemophilia A, who have received a single intravenous administration of SPK-8011 or SPK-8016 in any prior Spark-sponsored SPK-8011 or SPK-8016 study. Subjects will be followed for up to a total of 5 years post infusion (including the time on the dosing study).

Study Design

• Study Type: Observational
• Estimated Enrollment: 40 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: A Multi-Center Evaluation of the Long-Term Safety and Efficacy of Spark-sponsored Gene Therapies in Males With Hemophilia A
• Actual Study Start Date: August 14, 2018
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2022

Groups and Cohorts

Intervention Details:

• Genetic: SPK-8011
  Observational long-term safety follow-up study of subjects previously treated with SPK-8011 in any Spark-sponsored SPK-8011 study

Outcome Measures

Primary Outcome Measures :

1. Incidence of FVIII Inhibitors [ Time Frame: 4 years ]
   Incidence of FVIII Inhibitors
2. Incidence of all adverse events [ Time Frame: 4 years ]
   Incidence of all adverse events
3. Incidence(s) of new or exacerbation of adverse events of interest [ Time Frame: 4 years ]
   Such as: malignancies, neurologic, rheumatologic or other autoimmune, or hematologic disorders
4. Annual bleeding rate [ Time Frame: 4 years ]
   Annual bleeding rate
5. FVIII activity levels [ Time Frame: 4 years ]
   FVIII activity levels
6. Total FVIII consumption [ Time Frame: 4 years ]
   Total FVIII consumption
7. Number of FVIII infusions [ Time Frame: 4 years ]
   Number of FVIII infusions

Secondary Outcome Measures :

1. Joint Health Assessment [ Time Frame: 4 years ]
   Assessment of joint health for six index joints using a modified Hemophilia Joint Health Score (HJHS). The HJHS is a physical examination assessment tool, that measures joint health in the domain of body structure and function (i.e. impairment), of the joints most commonly affected by bleeding in hemophilia: the knees, ankles, and elbows
2. Target Joint Assessment [ Time Frame: 4 years ]
   Investigator assessment of bleeding in target joints (e.g., hip, elbow, wrist, shoulder, knee, and ankle)
3. Haem-A-QoL [ Time Frame: 4 years ]
   Quality-of-life (QoL) assessment
4. EQ-5D-5L [ Time Frame: 4 years ]
   Quality-of-life (QoL) assessment
5. Activities Assessments [ Time Frame: 4 years ]
   Hemophilia Activities List
6. Health Economics Assessment [ Time Frame: 4 years ]
   Collection of information including number of hospitalizations, emergency room visits, physician visits and work/school days missed

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Genetic males
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Males with hemophilia A, who received a single intravenous administration of SPK-8011 in any Spark-sponsored SPK-8011 study.

Criteria

Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply:

1. Have received a single intravenous administration of SPK-8011 or SPK-8016 in any Spark-sponsored gene therapy study; and
2. Understand the purpose and risks of the study and provide signed and dated informed consent before undergoing any study-specific procedures.

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

1.Unable or unwilling to comply with the schedule of visits and study assessments as described in this study protocol.

Contacts and Locations

Locations

United States, Massachusetts

Boston Children's Hospital

Boston, Massachusetts, United States, 02115

United States, Mississippi

Mississippi Center for Advanced Medicine

Madison, Mississippi, United States, 39110

United States, Missouri

Truman Medical Centers

Kansas City, Missouri, United States, 64108

United States, Oregon

Oregon Health & Science University

Portland, Oregon, United States, 97239

United States, Pennsylvania

Pennsylvania State University Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States, 10733

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

Thomas Jefferson University

Philadelphia, Pennsylvania, United States, 19107

Hemophilia Center of Western Pennsylvania

Pittsburgh, Pennsylvania, United States, 15213

United States, Virginia

Virginia Commonwealth University

Richmond, Virginia, United States, 23298

Australia, New South Wales

Royal Prince Alfred Hospital Department of Cell & Molecular Therapies

Sydney, New South Wales, Australia, 2050

Sponsors and Collaborators

Spark Therapeutics

Investigators

• Study Director: Clinical Trial Director; Spark Therapeutics, Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

George LA, Monahan PE, Eyster ME, Sullivan SK, Ragni MV, Croteau SE, Rasko JEJ, Recht M, Samelson-Jones BJ, MacDougall A, Jaworski K, Noble R, Curran M, Kuranda K, Mingozzi F, Chang T, Reape KZ, Anguela XM, High KA. Multiyear Factor VIII Expression after AAV Gene Transfer for Hemophilia A. N Engl J Med. 2021 Nov 18;385(21):1961-1973. doi: 10.1056/NEJMoa2104205.

• Responsible Party: Spark Therapeutics
• ClinicalTrials.gov Identifier: NCT03432520
• Other Study ID Numbers: SPK-8011/8016-LTFU
• First Posted: February 14, 2018
• Last Update Posted: February 10, 2022
• Last Verified: February 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hemophilia A; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn