Ascending Dose Study of Genome Editing by Zinc Finger Nuclease Therapeutic SB-FIX in Subjects With Severe Hemophilia B
A Phase I, Open-Label, Ascending Dose Study to Assess the Safety and Tolerability of AAV2/6 Factor IX Gene Therapy Via Zinc Finger Nuclease (ZFN) Mediated Targeted Integration of SB-FIX in Adult Subjects With Severe Hemophilia B
1 other identifier
interventional
1
1 country
1
Brief Summary
The purpose of the study is to evaluate the safety, tolerability and effect on FIX antigen and activity levels of ascending doses of SB-FIX. SB-FIX is an intravenously delivered Zinc Finger Nuclease (ZFN) Therapeutic for genome editing. It inserts a correct copy of the Factor 9 gene into the albumin locus in hepatocytes with the goal of lifelong therapeutic production of the Factor IX clotting factor.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Nov 2016
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 24, 2016
CompletedFirst Posted
Study publicly available on registry
March 1, 2016
CompletedStudy Start
First participant enrolled
November 15, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 19, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
April 19, 2021
CompletedResults Posted
Study results publicly available
July 19, 2024
CompletedJuly 19, 2024
February 1, 2024
4.4 years
February 24, 2016
April 14, 2022
February 7, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants With Treatment Related Adverse Events in Subjects Who Received SB-FIX as Assessed by Common Terminology Criteria for Adverse Events (CTCAE)
Number of Participants with Treatment Related Adverse Events in Subjects Who Received SB-FIX as Assessed by Common Terminology Criteria for Adverse Events (CTCAE).
Up to 36 months after the SB-FIX infusion
Secondary Outcomes (7)
Change From Baseline in Factor 9 Antigen Levels Measured in IU/mL and Factor 9 Activity Levels Measured in IU/mL at Week 28 After SB-FIX Infusion
From screening through to week 28 after SB-FIX infusion
Use of Factor IX Replacement Therapy
From baseline through 36 months after the SB-FIX infusion
Frequency and Severity of Bleeding Episodes
From baseline through 36 months after the SB-FIX infusion
Immune Response to FIX
Change from baseline through 28 weeks after the SB-FIX infusion
Presence of Shedding of AAV2/6 Vector DNA (in Copies/10 µL) by PCR in Plasma
From baseline through week 20 after SB-FIX infusion
- +2 more secondary outcomes
Study Arms (3)
Cohort 1
EXPERIMENTALSB-FIX: Low Dose
Cohort 2
EXPERIMENTALSB-FIX: Medium Dose
Cohort 3
EXPERIMENTALSB-FIX: High Dose
Interventions
Single dose of each of the 3 components of SB-FIX: ZFN1, ZFN2 and cDNA Donor.
Eligibility Criteria
You may qualify if:
- Male \>18 years of age
- Severe hemophilia B (native circulating FIX activity \<1%, with or without cross reactive material)
You may not qualify if:
- Presence of neutralizing antibodies
- History of hypersensitivity response or an allergic reaction to FIX or FIX products
- Currently receiving long acting FIX replacement therapy
- FIX mutations known to be associated with FIX inhibitors
- Polymorphisms in the ZFN target region
- Presence of any liver mass on MRI, or elevated alpha-fetoprotein (AFP)
- Any contraindication to the use of corticosteroids for immunosuppression
- Currently receiving antiviral therapy for hepatitis B or C or with history or active hepatitis B or hepatitis C or HIV-1 or HIV1/2 antibody positive.
- Chronic anemia, leukopenia, or thrombocytopenia
- Past medical history of active tuberculosis or significant fungal disease
- Symptomatic cardiovascular disease as a co-morbid condition
- Markers of hepatic inflammation or overt or occult cirrhosis
- History of chronic renal disease or creatinine ≥ 1.5 mg/dL
- Systemic (iv or oral) immunomodulatory agent or steroid use (topical treatment is allowed)
- History of chronic infection or other chronic disorder considered an unacceptable risk
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007, United States
Related Publications (1)
Harmatz P, Prada CE, Burton BK, Lau H, Kessler CM, Cao L, Falaleeva M, Villegas AG, Zeitler J, Meyer K, Miller W, Wong Po Foo C, Vaidya S, Swenson W, Shiue LH, Rouy D, Muenzer J. First-in-human in vivo genome editing via AAV-zinc-finger nucleases for mucopolysaccharidosis I/II and hemophilia B. Mol Ther. 2022 Dec 7;30(12):3587-3600. doi: 10.1016/j.ymthe.2022.10.010. Epub 2022 Oct 25.
PMID: 36299240DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Limitations and Caveats
Due to the limited sample size of 1 subject, the primary and secondary endpoints could not be analyzed, and this study could not report any conclusions.
Results Point of Contact
- Title
- Medical Monitor
- Organization
- Sangamo Therapeutics
Study Officials
- STUDY DIRECTOR
Medical Monitor
Sangamo Therapeutics, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 24, 2016
First Posted
March 1, 2016
Study Start
November 15, 2016
Primary Completion
April 19, 2021
Study Completion
April 19, 2021
Last Updated
July 19, 2024
Results First Posted
July 19, 2024
Record last verified: 2024-02
Data Sharing
- IPD Sharing
- Will not share