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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 : March 30, 2018
Sponsor:
Information provided by (Responsible Party):
Sangamo Therapeutics

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 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
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine


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.




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. 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 ]


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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

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


Contacts
Contact: Medical Monitor clinicaltrials@sangamo.com

Locations
United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Nadia P Ewing, MD         
Contact: Janice Kim    626-256-4673 ext 64350    jankim@coh.org   
Principal Investigator: Nadia P Ewing, MD         
Orthopaedic Institute for Children, Orthopaedic Hemophilia Treatment Center Recruiting
Los Angeles, California, United States, 90007
Contact: Doris Quon    213-742-1402    GEspinoza@mednet.ucla.edu   
Principal Investigator: Doris Quon, MD         
Quest Clinical Research Withdrawn
San Francisco, California, United States, 94115
United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: Tiffany Pearce    313-916-1784    Tpearce1@hfhs.org   
Principal Investigator: Philip Kuriakose, MD         
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Sponsors and Collaborators
Sangamo Therapeutics
Investigators
Study Director: Medical Monitor Sangamo Therapeutics, Inc.

Responsible Party: Sangamo Therapeutics
ClinicalTrials.gov Identifier: NCT02695160     History of Changes
Other Study ID Numbers: SB-FIX-1501
First Posted: March 1, 2016    Key Record Dates
Last Update Posted: March 30, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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