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

Hemophilia B Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02695160
• Other study ID #: SB-FIX-1501
• Status: Terminated
• Phase: Phase 1
• Start date: November 15, 2016
• Est. completion date: April 19, 2021

Study information

• Verified date: March 2022
• Source: Sangamo Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: April 19, 2021
• Est. primary completion date: April 19, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Biological:
• SB-FIX
Single dose of each of the 3 components of SB-FIX: ZFN1, ZFN2 and cDNA Donor.

Locations

Country	Name	City	State
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Sangamo Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change from baseline in FIX antigen and activity levels		up to 36 months after the SB-FIX infusion
Secondary	Change from baseline in use of Factor IX replacement therapy	• Change from baseline in the number of FIX units infused per week	Baseline and up to 36 months after the SB-FIX infusion
Secondary	Change from baseline in frequency and severity of bleeding episodes		Up to 36 months after the SB-FIX infusion
Secondary	Immune response to FIX	• Change in neutralizing antibodies to FIX from baseline over time	Up to 36 months after the SB-FIX infusion
Secondary	Presence and shedding of AAV2/6 vector DNA by PCR in plasma, saliva, urine, stool and semen		Follow up until 2 consecutive measurements are negative of AAV