Clinical trial NCT03061201: A Study of Recombinant AAV2/6 Human Factor 8 Gene Therapy SB-525 (PF-07055480) in Subjects With Severe Hemophilia A
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hemophilia A
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2017-02-23
Enrollment: 13
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Dose selection based on safety and kinetics of circulating FVIII levels observed in previously dosed participants.
Primary purpose: TREATMENT

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)

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.

Eligibility 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

Primary outcomes:
measure: Incidence of adverse events and serious adverse events
timeFrame: Up to 5 years after SB-525 (PF-07055480) infusion
measure: Changes in circulating FVIII activity
timeFrame: Up to 5 years after SB-525 (PF-07055480) infusion
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Sacramento
country: United States
facility: Midtown Ambulatory Care Center
state: California
city: Sacramento
country: United States
facility: UC Davis Ambulatory Care Clinic
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: UC Davis CTSC Clinical Research Center
state: California
city: Sacramento
country: United States
facility: UC Davis Hemophilia Treatment Center
state: California
city: Sacramento
country: United States
facility: UC Davis Investigational Drug Services Pharmacy
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco - Investigational Drug Service (IDS) Pharmacy
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco - Outpatient Hematology Clinic
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco -Moffitt Hospital
state: California
city: Miami
country: United States
facility: University Of Miami Hospital and Clinics/Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: USF Health Morsani Center For Advanced Healthcare
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Pittsburgh
country: United States
facility: Hemophilia Center of Western PA
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Montefiore Clinical and Translational Research Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC, Investigational Drug Service
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center Clinical Research Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Hemostasis Treatment Clinic
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Hemostasis-Thrombosis Clinic
state: Tennessee
city: Seattle
country: United States
facility: Washington Institute for Coagulation
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: