Hemophilia BPhase 1NCT02695160
Ascending Dose Study of Genome Editing by Zinc Finger Nuclease Therapeutic SB-FIX in Subjects With Severe Hemophilia B
A Phase 1 study testing SB-FIX in people with Hemophilia B, run by Sangamo Therapeutics at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Hemophilia B
- What is being tested?
- SB-FIX
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Nov 2016to 19 Apr 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male >18 years of age
- Severe hemophilia B (native circulating FIX activity <1%, with or without cross reactive material)
Who cannot join
- 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)
Show all 21Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
About this study
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
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.
Read the 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.
- Conditions
- Hemophilia B
- Being tested
- SB-FIX
- Medical subject headings
- Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SB-FIXBiological
Single dose of each of the 3 components of SB-FIX: ZFN1, ZFN2 and cDNA Donor.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | SB-FIX: Low Dose Receives: Biological: SB-FIX |
| Cohort 2 | Experimental | SB-FIX: Medium Dose Receives: Biological: SB-FIX |
| Cohort 3 | Experimental | SB-FIX: High Dose Receives: Biological: SB-FIX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Related Adverse Events in Subjects Who Received SB-FIX as Assessed by Common Terminology Criteria for Adverse Events (CTCAE)
Number of Participants with Treatment Related Adverse Events in Subjects Who Received SB-FIX as Assessed by Common Terminology Criteria for Adverse Events (CTCAE).
Measured: Up to 36 months after the SB-FIX infusion
Secondary outcomes (7)
Change From Baseline in Factor 9 Antigen Levels Measured in IU/mL and Factor 9 Activity Levels Measured in IU/mL at Week 28 After SB-FIX Infusion
FIX antigen levels measured in IU/mL using Enzyme-Linked Immunosorbent Assay (ELISA).
FIX activity levels measured in IU/mL using One-Stage Clot.
Measured: From screening through to week 28 after SB-FIX infusion
Use of Factor IX Replacement Therapy
Participants received a single intravenous infusion of SB-FIX which is formed of 3 components (ZFN1, ZFN2, and cDNA donor) in 200mL of diluent adjusted to 0.25% human serum albumin on day 0 over a period of 2-8 hours.
Measured: From baseline through 36 months after the SB-FIX infusion
Frequency and Severity of Bleeding Episodes
The number and severity of bleeding events were collected from 3 weeks post-SB-FIX treatment, and for 120 weeks thereafter.
Measured: From baseline through 36 months after the SB-FIX infusion
Immune Response to FIX
Neutralizing antibodies to FIX measured by FIX inhibitor levels using Nijmegen-Bethesda assays.
Measured: Change from baseline through 28 weeks after the SB-FIX infusion
Presence of Shedding of AAV2/6 Vector DNA (in Copies/10 µL) by PCR in Plasma
Two laboratory tests were run: AAV2/6-ZFN 42906 and AAV2/6-hF9. Presence in plasma was measured in number of copies/10 µL of whole plasma.
Measured: From baseline through week 20 after SB-FIX infusion
Presence and Shedding of AAV2/6 Vector DNA (in Copies/100ng) by PCR in Saliva, Stool and Semen
Subject data were collected at baseline and post infusion. Two laboratory tests were run for each sample type: AAV2/6-ZFN 42906 and AAV2/6-hF9. The presence of AAV2/6 vector DNA in saliva and stool was measured in number of copies/100 ng of sample DNA.
Measured: From baseline through week 20 after SB-FIX infusion
Presence and Shedding of AAV2/6 Vector DNA (in Copies/250 µL) by PCR in Urine
Two laboratory tests were run: AAV2/6-ZFN 42906 and AAV2/6-hF9. Its presence in urine was measured in number of copies/250 µL of whole urine.
Measured: From baseline through week 12 after SB-FIX infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2016 (estimated)
- Study start15 Nov 2016
- Primary completion19 Apr 2021
- Study completion19 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hemophilia BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sangamo Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Sangamo Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02695160
- Sponsor's protocol ID
- SB-FIX-1501
- Status last verified
- Feb 2024
- First submitted
- 24 Feb 2016
- Last updated
- 19 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Harmatz P, Prada CE, Burton BK, Lau H, Kessler CM, Cao L, Falaleeva M, Villegas AG, Zeitler J, Meyer K, Miller W, Wong Po Foo C, Vaidya S, Swenson W, Shiue LH, Rouy D, Muenzer J. First-in-human in vivo genome editing via AAV-zinc-finger nucleases for mucopolysaccharidosis I/II and hemophilia B. Mol Ther. 2022 Dec 7;30(12):3587-3600. doi: 10.1016/j.ymthe.2022.10.010. Epub 2022 Oct 25.
PubMed 36299240
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02695160
- Acronym / sponsor ID
- SB-FIX-1501
- Conditions
- Hemophilia B
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Sangamo TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 15 Nov 2016 (actual)
- Primary completion
- 19 Apr 2021 (actual)
- Study completion
- 19 Apr 2021 (actual)
- First posted
- 1 Mar 2016 (estimated)
- Results
- Posted 19 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: SB-FIXSB-FIX: Low Dose |
| Cohort 2 | Experimental | Biological: SB-FIXSB-FIX: Medium Dose |
| Cohort 3 | Experimental | Biological: SB-FIXSB-FIX: High Dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Male >18 years of age
- Severe hemophilia B (native circulating FIX activity <1%, with or without cross reactive material)
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SB-FIXSingle dose of each of the 3 components of SB-FIX: ZFN1, ZFN2 and cDNA Donor. | Biological | Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
Number of Participants With 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
Number of Participants with Treatment Related Adverse Events in Subjects Who Received SB-FIX as Assessed by Common Terminology Criteria for Adverse Events (CTCAE).
7 secondary outcomes
Change From Baseline in Factor 9 Antigen Levels Measured in IU/mL and Factor 9 Activity Levels Measured in IU/mL at Week 28 After SB-FIX Infusion
Time frame: From screening through to week 28 after SB-FIX infusion
Use of Factor IX Replacement Therapy
Time frame: From baseline through 36 months after the SB-FIX infusion
Frequency and Severity of Bleeding Episodes
Time frame: From baseline through 36 months after the SB-FIX infusion
Immune Response to FIX
Time frame: Change from baseline through 28 weeks after the SB-FIX infusion
Presence of Shedding of AAV2/6 Vector DNA (in Copies/10 µL) by PCR in Plasma
Time frame: From baseline through week 20 after SB-FIX infusion
Presence and Shedding of AAV2/6 Vector DNA (in Copies/100ng) by PCR in Saliva, Stool and Semen
Time frame: From baseline through week 20 after SB-FIX infusion
Presence and Shedding of AAV2/6 Vector DNA (in Copies/250 µL) by PCR in Urine
Time frame: From baseline through week 12 after SB-FIX infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36299240Harmatz P, Prada CE, Burton BK, Lau H, Kessler CM, Cao L, Falaleeva M, Villegas AG, Zeitler J, Meyer K, Miller W, Wong Po Foo C, Vaidya S, Swenson W, Shiue LH, Rouy D, Muenzer J. First-in-human in vivo genome editing via AAV-zinc-finger nucleases for mucopolysaccharidosis I/II and hemophilia B. Mol Ther. 2022 Dec 7;30(12):3587-3600. doi: 10.1016/j.ymthe.2022.10.010. Epub 2022 Oct 25.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Sangamo Therapeutics, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SB-FIX in people with Hemophilia B, run by Sangamo Therapeutics at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02695160, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2024.