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

A PHASE 1/2, OPEN-LABEL, ADAPTIVE, DOSE-RANGING STUDY TO ASSESS THE SAFETY AND TOLERABILITY OF SB-525 (PF-07055480) (RECOMBINANT AAV2/6 HUMAN FACTOR 8 GENE THERAPY) IN ADULT SUBJECTS WITH SEVERE HEMOPHILIA A

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)

Study Overview

• Status: Completed
• Conditions: Hemophilia A
• Intervention / Treatment: Biological: SB-525 (PF-07055480)

Detailed Description

The proposed 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 (PF-07055480) 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 (PF-07055480) administration may provide potential benefit in durable protection against bleeding and the complications thereof without lifelong repetitive IV factor replacement administration.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis CTSC Clinical Research Center
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center
    • Sacramento, California, United States, 95817
      • UC Davis Hemophilia Treatment Center
    • Sacramento, California, United States, 95817
      • Midtown Ambulatory Care Center
    • Sacramento, California, United States, 95817
      • UC Davis Ambulatory Care Clinic
    • Sacramento, California, United States, 95817
      • UC Davis Investigational Drug Services Pharmacy
    • San Francisco, California, United States, 94143
      • University of California, San Francisco - Outpatient Hematology Clinic
    • San Francisco, California, United States, 94143-0622
      • University of California, San Francisco - Investigational Drug Service (IDS) Pharmacy
    • San Francisco, California, United States, 94143
      • University of California, San Francisco -Moffitt Hospital
  • Florida
    • Miami, Florida, United States, 33136
      • University Of Miami Hospital and Clinics/Sylvester Comprehensive Cancer Center
    • Tampa, Florida, United States, 33612
      • USF Health Morsani Center For Advanced Healthcare
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Hemophilia Center of Western PA
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Montefiore Clinical and Translational Research Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC, Investigational Drug Service
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Hemostasis-Thrombosis Clinic
    • Nashville, Tennessee, United States, 37212-8646
      • Vanderbilt University Medical Center Clinical Research Center
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Hemostasis Treatment Clinic
  • Washington
    • Seattle, Washington, United States, 98101
      • Washington Institute for Coagulation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequential dose escalation; SB-525 (PF-07055480) is administered as a single infusion	Biological: SB-525 (PF-07055480); Single dose of investigational product SB-525 (PF-07055480)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Annualized Bleeding Rate (ABR)	Total ABR included both treated and untreated bleeding episodes. In this outcome measure total ABR for pre-screening and post-infusion are reported. Pre-screening total ABR was based on the total number of reported bleeding episodes during 12 months prior to screening visit as reported on CRF's Hemophilia A History page. Screening was 2 months before baseline. Post- infusion total ABR = number of all bleeding episodes starting 3 weeks after investigational product/ PF-07055480 (IP) infusion up to date of day before start of prophylaxis (or date of data cut or conclusion date)/ observation period in years, where observation period in years = date of day before start of prophylaxis or date of data cut or conclusion date - 3 weeks after date of IP infusion + 1)/365.25. For a participant who did not start prophylaxis the data cut date or conclusion date is used.	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	Total ABR include both treated and untreated bleeding episodes. In this outcome measure total ABR by severity for post-infusion period is reported. Severity was categorized as mild, moderate and severe. Post- infusion total ABR = number of all bleeding episodes starting 3 weeks after IP infusion up to date of day before start of prophylaxis (or date of data cut or conclusion date)/ observation period in years, where observation period in years = date of day before start of prophylaxis or date of data cut or conclusion date - 3 weeks after date of IP infusion + 1)/365.25. For a participant who did not start prophylaxis the data cut date or conclusion date is used.	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)	AIR was calculated and reported for pre-infusion and post-infusion. AIR for pre-infusion was calculated as, a) Excluding prophylaxis: number of FVIII replacement infusions for reasons other than prophylaxis prior to IP infusion/ ([date of IP infusion - date of screening] + 30)] *365.25, or b) number of FVIII replacement infusions for any reason prior to IP infusion/ ([date of IP infusion - date of screening] + 30)] *365.25. Screening was 2 months before baseline and baseline was approximately 1-week prior to IP infusion. AIR for post- infusion was calculated as: number of FVIII replacement infusions started at 3 weeks after IP infusion up to date of data cut or conclusion date/ number of days in the observation period for the participant in years, where observation period in years = date of data cut or conclusion date - 3 weeks after date of IP infusion + 1)/365.25.	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	EQ-5D-5L is a standardized measure of health status developed by the EuroQol Group. It measures 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) of health on a 5-point scale. Each dimension had 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. EQ-5D-5L had 2 components: Index score and visual analogue scale (VAS). Index score was obtained, according to the health state defined by the 5 dimensions scores, from the Crosswalk Index value calculator and table lookup document under the target country population. A health state is defined by the combination of one level from each of the 5 dimensions. For this study, weights under the US population were used to obtain the Index score. Index score ranged between 0-1, where higher score indicates a better health state, and lower score indicate worse health state. Baseline was defined as the latest non-missing value before IP infusion.	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	EQ-5D-5L is a standardized measure of health status developed by the EuroQol Group. It measures 5 dimensions of health on a 5-point scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is assessed with 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. EQ-5D-5L had 2 components: Index score and VAS. EQ-5D-5L VAS: Participants were asked to indicate their current health status on a scale of 0 (worst health) to 100 (best imaginable health), higher scores signified better health status. Baseline was defined as the latest non-missing value before IP infusion.	Baseline; Weeks 12, 24, and 52; Months 24, 36, 48, and 60
Number of Participants With Positive FVIII Inhibitor Levels During the Study	Positive FVIII inhibitor was assessed using central laboratory using Nijmegen method of the Bethesda assay in an individual with no prior history of FVIII inhibitor. Inhibitor assay results >0.6 Bethesda units (BU) were considered as positive. Positive results at any timepoint were considered, even if subsequent inhibitor assessment was negative.	Baseline (one week prior to IP infusion) up to 5 years post-infusion
Peak Value of AAV2/6 (Adeno-associated Vector 2/6) Deoxyribonucleic Acid (DNA) in Plasma, Saliva, Semen, Stool and Urine	Peak (maximum) AAV2/6 vector DNA concentration (vg/mL) in plasma, saliva, semen, stool and urine were analyzed with quantitative real-time polymerase chain reaction (PCR). Participants must achieve 3 consecutive negative results for analysis for each sample.	All samples: Baseline, Day 7, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and every month after Week 52 until Month 60 until 3 consecutive negative samples are obtained on a sample-type basis; additional for plasma at 12 hours post-infusion
Time to Peak Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine	Time to peak (maximum) AAV2/6 vector DNA concentration (vg/mL) in plasma, saliva, urine, stool and semen were analyzed with quantitative real-time PCR. Participants must achieve 3 consecutive negative results for analysis for each sample; where negative suggests values under the limit of detection.	All samples: Baseline, Day 7, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and every month after Week 52 until Month 60 until 3 consecutive negative samples are obtained on a sample-type basis; additional for plasma at 12 hours post-infusion
Time to Undetectable (Negative) Value of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine	Time to undetectable (negative) value of AAV2/6 vector DNA concentration (vg/mL) in plasma, saliva, urine, stool and semen were analyzed with quantitative real-time PCR. Time to undetectable is defined as the number of days from IP infusion until the first of 3 consecutive specimens under the limit of detection (negative).	All samples: Baseline, Day 7, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and every month after Week 52 until Month 60 until 3 consecutive negative samples are obtained on a sample-type basis; additional for plasma at 12 hours post-infusion
Time to Last of 3 Consecutive Negative Values of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine	Time to last of 3 consecutive negative value of AAV2/6 vector DNA concentration (vg/mL) in plasma, saliva, urine, stool and semen were analyzed with quantitative real-time PCR.	All samples: Baseline, Day 7, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and every month after Week 52 until Month 60 until 3 consecutive negative samples are obtained on a sample-type basis; additional for plasma at 12 hours post-infusion
Time to Last Positive Value Prior to First of 3 Consecutive Negatives of AAV2/6 Vector DNA in Plasma, Saliva, Semen, Stool and Urine	Time to last positive value prior to first of 3 consecutive negatives of AAV2/6 vector DNA concentration (vg/mL) in plasma, saliva, urine, stool and semen were analyzed with quantitative real-time PCR, where positive suggests values above the limit of detection.	All samples: Baseline, Day 7, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and every month after Week 52 until Month 60 until 3 consecutive negative samples are obtained on a sample-type basis; additional for plasma at 12 hours post-infusion

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2017
• Primary Completion (Actual): July 16, 2024
• Study Completion (Actual): July 16, 2024

Study Registration Dates

• First Submitted: February 15, 2017
• First Submitted That Met QC Criteria: February 17, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Estimated): September 30, 2025
• Last Update Submitted That Met QC Criteria: September 9, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hemophilia A
• Other Study ID Numbers: SB-525-1603; C3731001 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No