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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | SB-FIX: Low Dose |
|
| Cohort 2 | Experimental | SB-FIX: Medium Dose |
|
| Cohort 3 | Experimental | SB-FIX: High Dose |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SB-FIX | Biological | Single dose of each of the 3 components of SB-FIX: ZFN1, ZFN2 and cDNA Donor. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Up to 36 months after the SB-FIX infusion |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From screening through to week 28 after SB-FIX infusion |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Sangamo Therapeutics, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Georgetown University Medical Center | Washington D.C. | District of Columbia | 20007 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36299240 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | High Dose | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
All subjects in this study who received any portion of the SB-FIX infusion
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| ID | Title | Description |
|---|---|---|
| BG000 | High Dose | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | All subjects in this study who received any portion of the SB-FIX infusion | Posted | Count of Participants | Participants | Up to 36 months after the SB-FIX infusion |
|
Up to 36 months after the SB-FIX infusion
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | High Dose | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Flushing | Vascular disorders | Non-systematic Assessment |
Due to the limited sample size of 1 subject, the primary and secondary endpoints could not be analyzed, and this study could not report any conclusions.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Monitor | Sangamo Therapeutics | +1 510 307 7266 | clinicaltrials@sangamo.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 20, 2020 | Apr 14, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 10, 2020 | Apr 14, 2022 | SAP_001.pdf |
| ID | Term |
|---|---|
| D002836 | Hemophilia B |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| 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. | 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. | 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. | 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. | 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. | 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. | From baseline through week 12 after SB-FIX infusion |
| years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Race (NIH/OMB) | Count of Participants | Participants | No |
|
| Height | Number | cm |
|
| Weight | Number | kg |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | 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. | All subjects in this study who received any portion of the SB-FIX infusion | Posted | Number | IU/mL | From screening through to week 28 after SB-FIX infusion |
|
|
|
| Secondary | 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. | All subjects in this study who received any portion of the SB-FIX infusion | Posted | Number | Infusion | From baseline through 36 months after the SB-FIX infusion |
|
|
|
| Secondary | 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. | All subjects in this study who received any portion of the SB-FIX infusion | Posted | Number | Events | From baseline through 36 months after the SB-FIX infusion |
|
|
|
| Secondary | Immune Response to FIX | Neutralizing antibodies to FIX measured by FIX inhibitor levels using Nijmegen-Bethesda assays. | All subjects in this study who received any portion of the SB-FIX infusion | Posted | Number | BU/mL | Change from baseline through 28 weeks after the SB-FIX infusion |
|
|
|
| Secondary | 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. | All subjects in this study who received any portion of the SB-FIX infusion | Posted | Count of Participants | Participants | From baseline through week 20 after SB-FIX infusion |
|
|
|
| Secondary | 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. | All subjects in this study who received any portion of the SB-FIX infusion | Posted | Count of Participants | Participants | From baseline through week 20 after SB-FIX infusion |
|
|
|
| Secondary | 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. | All subjects in this study who received any portion of the SB-FIX infusion | Posted | Count of Participants | Participants | From baseline through week 12 after SB-FIX infusion |
|
|
|
| 0 |
| 1 |
| 0 |
| 1 |
| 1 |
| 1 |
| Sinus Tachycardia | Cardiac disorders | Non-systematic Assessment |
|
| Chills | General disorders | Non-systematic Assessment |
|
| Headache | Nervous system disorders | Non-systematic Assessment |
|
| Pyrexia | General disorders | Non-systematic Assessment |
|
All proposed written materials related to the study or an outline of proposed oral presentations, shall be submitted to Sangamo for approval at least 30 days prior to submission of materials for publication or oral disclosure to a third party. If Sangamo determines that a description of patentable subject matter is contained in written material or outline, it shall notify the clinical site within 1 month after receipt and Sangamo will have an additional 60 days for further review and action.
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D040181 | Genetic Diseases, X-Linked |
| Title | Measurements |
|---|---|
|
|
| Stool: AAV2/6-hF9 at week 12: <10 copies/100ng |
|
| Semen: AAV2/6-ZFN42906 at week 20: <20 copies/100ng |
|
| Semen: AAV2/6-hF9 at week 20: <20 copies/100ng |
|