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Ascending Dose Study of Genome Editing by Zinc Finger Nuclease Therapeutic SB-FIX in Subjects With Severe Hemophilia B

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02695160
Recruitment Status : Terminated
First Posted : March 1, 2016
Last Update Posted : March 23, 2022
Sponsor:
Information provided by (Responsible Party):
Sangamo Therapeutics

Study Description
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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.

Condition or disease Intervention/treatment Phase
Hemophilia B Biological: SB-FIX Phase 1

Detailed Description:
The objective of the study is to provide long term expression of Factor IX in subjects with severe hemophilia B. SB-FIX is a therapeutic for ZFN-mediated genome editing which will be delivered by adeno-associated virus (AAV)-derived vectors. SB-FIX is intended to function by placement of a corrective copy of the Factor IX transgene into the genome of the subject's own hepatocytes, under the control of the highly expressed endogenous albumin locus, and is expected to provide permanent, liver-specific expression of Factor IX for the lifetime of a hemophilia B subject.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 15, 2016
Actual Primary Completion Date : April 19, 2021
Actual Study Completion Date : April 19, 2021

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort 1
SB-FIX: Low Dose
 Biological: SB-FIX
Single dose of each of the 3 components of SB-FIX: ZFN1, ZFN2 and cDNA Donor.
Experimental: Cohort 2
SB-FIX: Medium Dose
 Biological: SB-FIX
Single dose of each of the 3 components of SB-FIX: ZFN1, ZFN2 and cDNA Donor.
Experimental: Cohort 3
SB-FIX: High Dose
 Biological: SB-FIX
Single dose of each of the 3 components of SB-FIX: ZFN1, ZFN2 and cDNA Donor.


Outcome Measures
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Primary Outcome Measures :
  1. Treatment related Adverse Events in subjects who received SB-FIX as assessed by Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 36 months after the SB-FIX infusion ]

Secondary Outcome Measures :
  1. Change from baseline in FIX antigen and activity levels [ Time Frame: up to 36 months after the SB-FIX infusion ]
  2. Change from baseline in use of Factor IX replacement therapy [ Time Frame: Baseline and up to 36 months after the SB-FIX infusion ]
    • Change from baseline in the number of FIX units infused per week

  3. Change from baseline in frequency and severity of bleeding episodes [ Time Frame: Up to 36 months after the SB-FIX infusion ]
  4. Immune response to FIX [ Time Frame: Up to 36 months after the SB-FIX infusion ]
    • Change in neutralizing antibodies to FIX from baseline over time

  5. Presence and shedding of AAV2/6 vector DNA by PCR in plasma, saliva, urine, stool and semen [ Time Frame: Follow up until 2 consecutive measurements are negative of AAV ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male >18 years of age
  • Severe hemophilia B (native circulating FIX activity <1%, with or without cross reactive material)

Exclusion Criteria:

  • 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
  • History of malignancy except for treated basal cell or squamous cell carcinoma
  • History of alcohol or substance abuse
  • Previously received gene therapy product
  • Participation in prior investigational drug or medical device study within the previous 3 months
  • History of therapeutic non-adherence
  • Any other reason that, in the opinion of the Investigator or Medical Monitor, would render the subject unsuitable for participation in the study
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02695160


Locations
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United States, District of Columbia
Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
Sponsors and Collaborators
Sangamo Therapeutics
Investigators
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Study Director: Medical Monitor Sangamo Therapeutics, Inc.
More Information
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Responsible Party: Sangamo Therapeutics
ClinicalTrials.gov Identifier: NCT02695160    
Other Study ID Numbers: SB-FIX-1501
First Posted: March 1, 2016    Key Record Dates
Last Update Posted: March 23, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
 Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked