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

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ClinicalTrials.gov Identifier: NCT02695160
Recruitment Status : Recruiting
First Posted : March 1, 2016
Last Update Posted : August 28, 2018
Sponsor:
Information provided by (Responsible Party):
Sangamo Therapeutics

February 24, 2016
March 1, 2016
August 28, 2018
November 15, 2016
January 2019   (Final data collection date for primary outcome measure)
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 ]
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 ]
Complete list of historical versions of study NCT02695160 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 ]
Not Provided
Not Provided
 
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
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.
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.
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Hemophilia B
Biological: SB-FIX
Single dose of each of the 3 components of SB-FIX: ZFN1, ZFN2 and cDNA Donor.
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
12
9
January 2021
January 2019   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: Male
18 Years and older   (Adult, Older Adult)
No
Contact: Medical Monitor clinicaltrials@sangamo.com
United States
 
 
NCT02695160
SB-FIX-1501
Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: No
Sangamo Therapeutics
Sangamo Therapeutics
Not Provided
Study Director: Medical Monitor Sangamo Therapeutics, Inc.
Sangamo Therapeutics
March 2018

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