A Study of Recombinant AAV2/6 Human Factor 8 Gene Therapy SB-525 (PF-07055480) in Subjects With Severe Hemophilia A

NCT03061201 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: SB-525-1603C3731001
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 22

Brief Summary

The purpose of the study is to evaluate the safety, tolerability and time-course profile of FVIII activity after dosing with SB-525 (PF-07055480)

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (21)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the criteria as follows: death, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect and other situations per protocol. AEs included both SAEs and all non-SAEs.

  From Baseline (1 week prior to infusion) up to 5 years post-infusion (approximately 5 Years)

• Central FVIII Activity Levels by Chromogenic Assay at Year 1 (Week 52)

  FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by chromogenic assay are reported.

  At Year 1 (Week 52)

• Central FVIII Activity Levels by Chromogenic Assay at Year 2 (Week 104)

  FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by chromogenic assay are reported.

  At Year 2 (Week 104)

• Central FVIII Activity Levels by Chromogenic Assay at Year 3 (Week 156)

  FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by chromogenic assay are reported.

  At Year 3 (Week 156)

• Central FVIII Activity Levels by Chromogenic Assay at Year 4 (Week 208)

  FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by chromogenic assay are reported.

  At Year 4 (Week 208)

• Central FVIII Activity Levels by Chromogenic Assay at Year 5 (Week 260)

  FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by chromogenic assay are reported.

  At Year 5 (Week 260)

• Central FVIII Activity Levels by One-Stage Clotting Assay at Year 1 (Week 52)

  FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by one-stage clotting assay are reported.

  At Year 1 (Week 52)

• Central FVIII Activity Levels by One-Stage Clotting Assay at Year 2 (Week 104)

  FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by one-stage clotting assay are reported.

  At Year 2 (Week 104)

• Central FVIII Activity Levels by One-Stage Clotting Assay at Year 3 (Week 156)

  FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by one-stage clotting assay are reported.

  At Year 3 (Week 156)

• Central FVIII Activity Levels by One-Stage Clotting Assay at Year 4 (Week 208)

  FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by one-stage clotting assay are reported.

  At Year 4 (Week 208)

• Central FVIII Activity Levels by One-Stage Clotting Assay at Year 5 (Week 260)

  FVIII activity levels were assessed using chromogenic and one-stage clotting assay and which were analyzed in the central laboratory. In this outcome measure results by one-stage clotting assay are reported.

  At Year 5 (Week 260)

• Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 1 (Week 9 Through Week 53)

  FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by chromogenic assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 1 included assessments from Week 9 through Week 53). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.

  Year 1 (Week 9 through Week 53)

• Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 2 (Week 54 Through Week 108)

  FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by chromogenic assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 2 included assessments from Week 54 through Week 108). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.

  Year 2 (Week 54 through Week 108)

• Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 3 (Week 109 Through Week 160)

  FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by chromogenic assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 3 included assessments from Week 109 through Week 160). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.

  Year 3 (Week 109 through Week 160)

• Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 4 (Week 161 Through Week 212)

  FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by chromogenic assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 4 included assessments from Week 161 through Week 212). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.

  Year 4 (Week 161 through Week 212)

• Geometric Mean of Central FVIII Activity Levels for Cohort 4 by Chromogenic Assay at Yearly Interval 5 (Week 213 Through Week 264)

  FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by chromogenic assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 5 included assessments from Week 213 through Week 264). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.

  Year 5 (Week 213 through Week 264)

• Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 1 (Week 9 Through Week 53)

  FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by one-stage clotting assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 1 included assessments from Week 9 through Week 53). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.

  Year 1 (Week 9 through Week 53)

• Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 2 (Week 54 Through Week 108)

  FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by one-stage clotting assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 2 included assessments from Week 54 through Week 108). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.

  Year 2 (Week 54 through Week 108)

• Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 3 (Week 109 Through Week 160)

  FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by one-stage clotting assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 3 included assessments from Week 109 through Week 160). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.

  Year 3 (Week 109 through Week 160)

• Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 4 (Week 161 Through Week 212)

  FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by one-stage clotting assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 4 included assessments from Week 161 through Week 212). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.

  Year 4 (Week 161 through Week 212)

• Geometric Mean of Central FVIII Activity Levels for Cohort 4 by One-Stage Clotting Assay at Yearly Interval 5 (Week 213 Through Week 264)

  FVIII activity levels were analyzed in the central laboratory using chromogenic and one-stage clotting assay. In this outcome measure FVIII activity levels were assessed by one-stage clotting assay. As pre-specified, for each participant geometric mean of central FVIII activity levels was calculated of all eligible FVIII activity measurements for each yearly interval (for this outcome measure: Yearly Interval 5 included assessments from Week 213 through Week 264). Following this mean and standard deviation as summary statistics across all evaluable participants was calculated and is reported as data for this outcome measure.

  Year 5 (Week 213 through Week 264)

Secondary Outcomes (11)

• Total Annualized Bleeding Rate (ABR)

  Pre-screening period: 12 months prior to screening; Post-infusion period: 3 weeks post-infusion up to date of day before start of prophylaxis or date of data cut or conclusion date, whichever was earlier (maximum up to 5 years)

• Total ABR by Severity

  Post-infusion period: 3 weeks post-infusion up to date of day before start of prophylaxis or date of data cut or conclusion date, whichever was earlier (maximum up to 5 years)

• Annualized Infusion Rate (AIR)

  Pre-infusion period: 30 days before screening up to pre-infusion (approximately up to 3.23 months); post-infusion period: 3 weeks post-infusion up to up to date of data cut or conclusion date (maximum up to 5 years)

• Change From Baseline in the EuroQol, 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score at Weeks 12, 24 and 52; Months 24, 36, 48 and 60

  Baseline; Weeks 12, 24, and 52; Months 24, 36, 48, and 60

• Change From Baseline in the EQ-5D-5L- VAS Score at Week 12, 24, 52 and Month 24, 36, 48, 60

  Baseline; Weeks 12, 24, and 52; Months 24, 36, 48, and 60

Study Arms (1)

Sequential dose escalation

EXPERIMENTAL

SB-525 (PF-07055480) is administered as a single infusion

Biological: SB-525 (PF-07055480)

Interventions

SB-525 (PF-07055480) BIOLOGICAL

Single dose of investigational product SB-525 (PF-07055480)

Sequential dose escalation

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (22)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Midtown Ambulatory Care Center

Sacramento, California, 95817, United States

Location

UC Davis Ambulatory Care Clinic

Sacramento, California, 95817, United States

Location

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UC Davis CTSC Clinical Research Center

Sacramento, California, 95817, United States

Location

UC Davis Hemophilia Treatment Center

Sacramento, California, 95817, United States

Location

UC Davis Investigational Drug Services Pharmacy

Sacramento, California, 95817, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

University of California, San Francisco - Investigational Drug Service (IDS) Pharmacy

San Francisco, California, 94143-0622, United States

Location

University of California, San Francisco - Outpatient Hematology Clinic

San Francisco, California, 94143, United States

Location

University of California, San Francisco -Moffitt Hospital

San Francisco, California, 94143, United States

Location

University Of Miami Hospital and Clinics/Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

USF Health Morsani Center For Advanced Healthcare

Tampa, Florida, 33612, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Hemophilia Center of Western PA

Pittsburgh, Pennsylvania, 15213, United States

Location

UPMC Montefiore Clinical and Translational Research Center

Pittsburgh, Pennsylvania, 15213, United States

Location

UPMC, Investigational Drug Service

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt University Medical Center Clinical Research Center

Nashville, Tennessee, 37212-8646, United States

Location

Vanderbilt Hemostasis Treatment Clinic

Nashville, Tennessee, 37232, United States

Location

Vanderbilt Hemostasis-Thrombosis Clinic

Nashville, Tennessee, 37232, United States

Location

Washington Institute for Coagulation

Seattle, Washington, 98101, United States

Location

Related Publications (2)

• Leavitt AD, Konkle BA, Stine KC, Visweshwar N, Harrington TJ, Giermasz A, Arkin S, Fang A, Plonski F, Yver A, Ganne F, Agathon D, Resa MLA, Tseng LJ, Di Russo G, Cockroft BM, Cao L, Rupon J. Giroctocogene fitelparvovec gene therapy for severe hemophilia A: 104-week analysis of the phase 1/2 Alta study. Blood. 2024 Feb 29;143(9):796-806. doi: 10.1182/blood.2022018971.

  PMID: 37871576 DERIVED

• Cao L, Ledeboer A, Pan Y, Lu Y, Meyer K. Clinical enrollment assay to detect preexisting neutralizing antibodies to AAV6 with demonstrated transgene expression in gene therapy trials. Gene Ther. 2023 Feb;30(1-2):150-159. doi: 10.1038/s41434-022-00353-2. Epub 2022 Jul 1.

  PMID: 35778500 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

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

Limitations and Caveats

Any untoward clinically significant changes from pre vector dosing identified on physical examinations, clinical laboratory assessments, immune parameters, liver imaging, vital signs, Electrocardiogram during the during study were captured as AEs.

Results Point of Contact

• Title: Pfizer Clinical Trials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

18007181021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose selection based on safety and kinetics of circulating FVIII levels observed in previously dosed participants.

Study Record Dates

• First Submitted: February 15, 2017
• First Posted: February 23, 2017
• Study Start: June 21, 2017
• Primary Completion: July 16, 2024
• Study Completion: July 16, 2024
• Last Updated: September 30, 2025
• Results First Posted: September 30, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

US (22)