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Dose-Ranging Study of Recombinant AAV2/6 Human Factor 8 Gene Therapy SB-525 in Subjects With Severe Hemophilia A

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ClinicalTrials.gov Identifier: NCT03061201
Recruitment Status : Recruiting
First Posted : February 23, 2017
Last Update Posted : September 20, 2018
Sponsor:
Information provided by (Responsible Party):
Sangamo Therapeutics

Brief Summary:
The purpose of the study is to evaluate the safety, tolerability and time-course profile of FVIII activity levels with adaptive doses of SB-525.

Condition or disease Intervention/treatment Phase
Hemophilia A Biological: SB-525 Phase 1 Phase 2

Detailed Description:

The objective of the study is to reduce or eliminate the need for FVIII replacement therapy. The proposed SB-525 clinical study uses a recombinant adeno-associated virus 2/6 (AAV2/6) vector encoding the cDNA for the B-domain deleted human F8 (hF8). The secreted FVIII has the same amino acid sequence as approved recombinant anti hemophilic factors (Refacto® and Xyntha®). The SB-525 vector encodes a liver-specific promotor module and AAV2/6 exhibits liver tropism, thus providing the potential for long-term hepatic production of FVIII in hemophilia A subjects.

The constant production of FVIII after a single SB-525 administration may provide potential benefit in durable protection against bleeding and the complications thereof without lifelong repetitive IV factor replacement administration.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Sequential Assignment
Intervention Model Description: Dose selection based on safety and observed FVIII levels.
Masking: None (Open Label)
Masking Description: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open-Label, Adaptive, Dose-Ranging Study to Assess the Safety and Tolerability of SB-525 (Recombinant AAV2/6 Human Factor 8 Gene Therapy) in Adult Subjects With Severe Hemophilia A
Actual Study Start Date : June 2, 2017
Estimated Primary Completion Date : November 15, 2021
Estimated Study Completion Date : January 30, 2022


Arm Intervention/treatment
Experimental: Sequential dose escalation
SB-525 is administered as a single infusion
Biological: SB-525
Single dose of investigational product SB-525




Primary Outcome Measures :
  1. Number of treatment related adverse events as assessed by laboratory assessments and vital signs [ Time Frame: Up to 3 years after SB-525 infusion ]
  2. Changes in circulating FVIII activity [ Time Frame: Up to 3 years after SB-525 infusion ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male ≥18 years of age
  • Severe hemophilia A (past evidence of circulating FVIII activity of < 1% normal)
  • Treated or exposed to FVIII concentrates or cryoprecipitate for at least 150 exposure days
  • ≥12 bleeding episodes if receiving on-demand therapy over the preceding 12 months
  • Agree to use double barrier contraceptive until at least 3 consecutive semen samples are negative for AAV 2/6 after SB-525 infusion

Exclusion Criteria:

  • Presence of neutralizing antibodies
  • Current inhibitor, or history of FVIII inhibitor (except for transient low titer inhibitor detected in childhood)
  • History of hypersensitivity response to FVIII
  • History of Hepatitis B or HIV-1/2 infection
  • History of Hepatitis C, unless viral assays in two samples, collected at least 6 months apart, are negative
  • Evidence of any bleeding disorder in addition to hemophilia A
  • Markers of hepatic inflammation or overt or occult cirrhosis
  • History of chronic renal disease or creatinine ≥ 1.5 mg/dL
  • Presence of liver mass on magnetic resonance imaging (MRI), or, positive alpha fetoprotein
  • Presence of > grade 2 liver fibrosis on elastography for subjects with history of treated Hepatitis C or suspicion of chronic liver disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03061201


Contacts
Contact: Medical Monitor 510.307.7266 clinicaltrials@sangamo.com

Locations
United States, Arkansas
Arkansas Children's Hospital Recruiting
Little Rock, Arkansas, United States, 19406
Contact: Jocelyn Wright    501-364-2391    WrightJJ@archildrens.org   
United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Cara Nolan, CCRP    626-218-2341    canolan@coh.org   
UC Davis Medical Center Recruiting
Sacramento, California, United States, 95817
Contact: Adam Giermasz, MD    916-734-3469    skvasquez@ucdavis.edu   
University of California, San Francisco Recruiting
San Francisco, California, United States, 94117
Contact: Andrew Leavitt, MD    415-514-3432    Andrew.leavitt@ucsf.edu   
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Leandro Pisani    305-243-6925    lfp34@miami.edu   
University of South Florida Recruiting
Tampa, Florida, United States, 33612
Contact: Hazina Joseph    813-974-4048    hjoseph1@health.usf.edu   
Contact: Azam Rukhsana    813-974-7074    razam@health.usf.edu   
United States, Georgia
Emory University, Dept. of Hematology Recruiting
Atlanta, Georgia, United States, 30322
Contact: Stephanie Whitten    404-686-0277    stephanie.whitten@emoryhealthcare.org   
United States, Indiana
Indiana Hemophilia and Thrombosis Center, Inc. Recruiting
Indianapolis, Indiana, United States, 46260
Contact: Neelam Thukral, CCRC    317-871-0000 ext 373    nthukral@ihtc.org   
United States, Iowa
University of Iowa Hospitals & Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Meredith Wisniewski, RN BSN CPHON    319-678-8571    meredith-wisniewski@uiowa.edu   
United States, Pennsylvania
Hemophilia Center of Western PA Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Margaret Ragni, MD, MPH    412-209-7263    JKadosh@itxm.org   
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Alexandra Borst, MD    615-343-7123    carrie.greene@vumc.org   
United States, Washington
Bloodworks Recruiting
Seattle, Washington, United States, 98104
Contact: Barbara Konkle, MD    206-689-6191    BarbaraK@BloodworksNW.org   
Sponsors and Collaborators
Sangamo Therapeutics
Investigators
Study Director: Medical Monitor Sangamo Therapeutics, Inc.

Responsible Party: Sangamo Therapeutics
ClinicalTrials.gov Identifier: NCT03061201     History of Changes
Other Study ID Numbers: SB-525-1603
First Posted: February 23, 2017    Key Record Dates
Last Update Posted: September 20, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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
Factor VIII
Coagulants