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Trial record 1 of 1 for:    SB-525-1603 | Recruiting Studies | Hemophilia A | United States
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Dose-Ranging Study of Recombinant AAV2/6 Human Factor 8 Gene Therapy SB-525 in Subjects With Severe Hemophilia A

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ClinicalTrials.gov Identifier: NCT03061201
Recruitment Status : Recruiting
First Posted : February 23, 2017
Last Update Posted : July 8, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE February 15, 2017
First Posted Date  ICMJE February 23, 2017
Last Update Posted Date July 8, 2020
Actual Study Start Date  ICMJE June 21, 2017
Estimated Primary Completion Date July 23, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 17, 2017)
  • Number of treatment related adverse events as assessed by laboratory assessments and vital signs [ Time Frame: Up to 3 years after SB-525 infusion ]
  • Changes in circulating FVIII activity [ Time Frame: Up to 3 years after SB-525 infusion ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: February 17, 2017)
  • Frequency of administration of FVIII replacement therapy after administration of SB-525 [ Time Frame: Up to 3 years from baseline and after SB-525 infusion ]
  • Number of bleeding episodes requiring treatment after the administration of SB-525 [ Time Frame: Up to 3 years from baseline and after SB-525 infusion ]
  • Change in the EQ-5D health outcome questionnaire [ Time Frame: Up to 1 year from baseline and after SB-525 infusion ]
  • Measurement of FVIII inhibitor level [ Time Frame: Up to 3 years after SB-525 infusion ]
  • Presence of AAV2/6 vector DNA in plasma, saliva, urine, stool and semen [ Time Frame: Up to 3 years after SB-525 infusion ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose-Ranging Study of Recombinant AAV2/6 Human Factor 8 Gene Therapy SB-525 in Subjects With Severe Hemophilia A
Official Title  ICMJE 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
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Sequential Assignment
Intervention Model Description:
Dose selection based on safety and observed FVIII levels.
Masking: None (Open Label)
Masking Description:
Open Label
Primary Purpose: Treatment
Condition  ICMJE Hemophilia A
Intervention  ICMJE Biological: SB-525
Single dose of investigational product SB-525
Study Arms  ICMJE Experimental: Sequential dose escalation
SB-525 is administered as a single infusion
Intervention: Biological: SB-525
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 25, 2020)
13
Original Estimated Enrollment  ICMJE
 (submitted: February 17, 2017)
20
Estimated Study Completion Date  ICMJE July 23, 2024
Estimated Primary Completion Date July 23, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Medical Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03061201
Other Study ID Numbers  ICMJE SB-525-1603
C3731001 ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP