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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03061201
Recruitment Status : Recruiting
First Posted : February 23, 2017
Last Update Posted : February 27, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

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 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 13 participants
Intervention Model: Parallel 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 21, 2017
Estimated Primary Completion Date : July 24, 2024
Estimated Study Completion Date : July 24, 2024

Resource links provided by the National Library of Medicine


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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
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
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Contact: Medical Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
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United States, Arkansas
Arkansas Children's Hospital Active, not recruiting
Little Rock, Arkansas, United States, 72202
United States, California
UC Davis Hemophilia Treatment Center Active, not recruiting
Sacramento, California, United States, 95817
UCSF Medical Center Active, not recruiting
San Francisco, California, United States, 94143-0106
United States, Florida
Sylvester Comprehensive Cancer Center Active, not recruiting
Miami, Florida, United States, 33136
University of South Florida Active, not recruiting
Tampa, Florida, United States, 33612
United States, Georgia
Winship Cancer Institute Not yet recruiting
Atlanta, Georgia, United States, 30322
United States, Iowa
University of Iowa Hospitals and Clinics, Iowa Regional Hemophilia Center Recruiting
Iowa City, Iowa, United States, 52242
United States, Washington
Bloodworks NW Active, not recruiting
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03061201    
Other Study ID Numbers: SB-525-1603
C3731001 ( Other Identifier: Alias Study Number )
First Posted: February 23, 2017    Key Record Dates
Last Update Posted: February 27, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn