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

Sponsor
Pfizer (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03061201
Collaborator
(none)
11
Enrollment
20
Locations
1
Arm
85.1
Anticipated Duration (Months)
0.6
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease Intervention/Treatment Phase
  • Biological: SB-525 (PF-07055480)
 Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
11 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Intervention Model Description:
Dose selection based on safety and kinetics of circulating FVIII levels observed in previously dosed participants.Dose selection based on safety and kinetics of circulating FVIII levels observed in previously dosed participants.
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 (PF-07055480) (RECOMBINANT AAV2/6 HUMAN FACTOR 8 GENE THERAPY) IN ADULT SUBJECTS WITH SEVERE HEMOPHILIA A
Actual Study Start Date :
Jun 21, 2017
Anticipated Primary Completion Date :
Jul 23, 2024
Anticipated Study Completion Date :
Jul 23, 2024

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

  1. Incidence of adverse events and serious adverse events [Up to 5 years after SB-525 (PF-07055480) infusion]

  2. Changes in circulating FVIII activity [Up to 5 years after SB-525 (PF-07055480) infusion]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Arkansas Children's Hospital Little Rock Arkansas United States 72202
2 City of Hope Medical Center Duarte California United States 91010
3 Midtown Ambulatory Care Center Sacramento California United States 95817
4 UC Davis Ambulatory Care Clinic Sacramento California United States 95817
5 UC Davis Comprehensive Cancer Center Sacramento California United States 95817
6 UC Davis CTSC Clinical Research Center Sacramento California United States 95817
7 UC Davis Hemophilia Treatment Center Sacramento California United States 95817
8 UC Davis Investigational Drug Services Pharmacy Sacramento California United States 95817
9 UC Davis Medical Center Sacramento California United States 95817
10 University of California, San Francisco - Investigational Drug Service (IDS) Pharmacy San Francisco California United States 94143-0622
11 University of California, San Francisco - Outpatient Hematology Clinic San Francisco California United States 94143
12 University of California, San Francisco -Moffitt Hospital San Francisco California United States 94143
13 University Of Miami Hospital and Clinics/Sylvester Comprehensive Cancer Center Miami Florida United States 33136
14 USF Health Morsani Center For Advanced Healthcare Tampa Florida United States 33612
15 Emory University School of Medicine Atlanta Georgia United States 30322
16 Hemophilia Center of Western PA Pittsburgh Pennsylvania United States 15213
17 UPMC Montefiore Clinical and Translational Research Center Pittsburgh Pennsylvania United States 15213
18 UPMC, Investigational Drug Service Pittsburgh Pennsylvania United States 15213
19 Vanderbilt Hemostasis-Thrombosis Clinic Nashville Tennessee United States 37232
20 Washington Institute for Coagulation Seattle Washington United States 98101

Sponsors and Collaborators

  • Pfizer

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT03061201
Other Study ID Numbers:
  • SB-525-1603
  • C3731001
First Posted:
Feb 23, 2017
Last Update Posted:
Dec 13, 2021
Last Verified:
Dec 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Hemophilia A

Study Results

No Results Posted as of Dec 13, 2021