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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 : Active, not recruiting
First Posted : March 1, 2016
Last Update Posted : July 2, 2019
Sponsor:
Information provided by (Responsible Party):
Sangamo Therapeutics

Tracking Information
First Submitted Date  ICMJE February 24, 2016
First Posted Date  ICMJE March 1, 2016
Last Update Posted Date July 2, 2019
Actual Study Start Date  ICMJE November 15, 2016
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 6, 2017)
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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 24, 2016)
Treatment related Adverse Events on subjects who received SB-FIX [ Time Frame: 8 weeks after the SB-FIX infusion of the last subject in each cohort and up to 36 months after the SB-FIX infusion ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 6, 2017)
  • Change from baseline in FIX antigen and activity levels [ Time Frame: up to 36 months after the SB-FIX infusion ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 24, 2016)
  • Effect of SB-FIX on FIX antigen and activity levels [ Time Frame: up to 36 months after the SB-FIX infusion ]
  • Effect of SB-FIX on the number of FIX units infused per week [ Time Frame: up to 36 months after the SB-FIX infusion ]
  • Effect of SB-FIX on neutralizing antibodies in serum [ Time Frame: up to 36 months after the SB-FIX infusion ]
  • Effect of SB-FIX on immunogenicity response to FIX [ Time Frame: up to 36 months after the SB-FIX infusion ]
  • Effect of SB-FIX on presence and shedding in AAV2/6 vector DNA [ Time Frame: up to 36 months after the SB-FIX infusion ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ascending Dose Study of Genome Editing by Zinc Finger Nuclease Therapeutic SB-FIX in Subjects With Severe Hemophilia B
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hemophilia B
Intervention  ICMJE Biological: SB-FIX
Single dose of each of the 3 components of SB-FIX: ZFN1, ZFN2 and cDNA Donor.
Study Arms  ICMJE
  • Experimental: Cohort 1
    SB-FIX: Low Dose
    Intervention: Biological: SB-FIX
  • Experimental: Cohort 2
    SB-FIX: Medium Dose
    Intervention: Biological: SB-FIX
  • Experimental: Cohort 3
    SB-FIX: High Dose
    Intervention: Biological: SB-FIX
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 Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: October 12, 2016)
12
Original Estimated Enrollment  ICMJE
 (submitted: February 24, 2016)
9
Estimated Study Completion Date  ICMJE January 2021
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT02695160
Other Study ID Numbers  ICMJE SB-FIX-1501
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sangamo Therapeutics
Study Sponsor  ICMJE Sangamo Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Monitor Sangamo Therapeutics, Inc.
PRS Account Sangamo Therapeutics
Verification Date February 2019

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