Trial Outcomes & Findings for Ascending Dose Study of Genome Editing by Zinc Finger Nuclease Therapeutic SB-FIX in Subjects With Severe Hemophilia B (NCT NCT02695160)

NCT ID: NCT02695160

Last Updated: 2024-07-19

Results Overview

Number of Participants with Treatment Related Adverse Events in Subjects Who Received SB-FIX as Assessed by Common Terminology Criteria for Adverse Events (CTCAE).

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

1 participants

Primary outcome timeframe

Up to 36 months after the SB-FIX infusion

Results posted on

2024-07-19

Participant Flow

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	1
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	High Dose n=1 Participants 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.
Age, Continuous	60 years STANDARD_DEVIATION 0 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Height	173 cm n=5 Participants
Weight	74.7 kg n=5 Participants

PRIMARY outcome

Timeframe: Up to 36 months after the SB-FIX infusion

Population: All subjects in this study who received any portion of 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).

Outcome measures

Outcome measures
Measure	High Dose n=1 Participants 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.
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 adverse events	1 Participants
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 serious adverse events	0 Participants

SECONDARY outcome

Timeframe: From screening through to week 28 after SB-FIX infusion

Population: All subjects in this study who received any portion of the 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.

Outcome measures

Outcome measures
Measure	High Dose n=1 Participants 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.
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 Change from baseline of FIX activity	0.003 IU/mL
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 Change from baseline of FIX antigen levels	-0.006 IU/mL

SECONDARY outcome

Timeframe: From baseline through 36 months after the SB-FIX infusion

Population: All subjects in this study who received any portion of the SB-FIX infusion

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.

Outcome measures

Outcome measures
Measure	High Dose n=1 Participants 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.
Use of Factor IX Replacement Therapy Total factor replacements	170 Infusion
Use of Factor IX Replacement Therapy Of which, purpose of treatment was recorded as prophylactic	45 Infusion
Use of Factor IX Replacement Therapy Of which, purpose of treatment was not recorded	125 Infusion

SECONDARY outcome

Timeframe: From baseline through 36 months after the SB-FIX infusion

Population: All subjects in this study who received any portion of the SB-FIX infusion

The number and severity of bleeding events were collected from 3 weeks post-SB-FIX treatment, and for 120 weeks thereafter.

Outcome measures

Outcome measures
Measure	High Dose n=1 Participants 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.
Frequency and Severity of Bleeding Episodes Moderate bleeding episodes	1 Events
Frequency and Severity of Bleeding Episodes Mild bleeding episodes	1 Events

SECONDARY outcome

Timeframe: Change from baseline through 28 weeks after the SB-FIX infusion

Population: All subjects in this study who received any portion of the SB-FIX infusion

Neutralizing antibodies to FIX measured by FIX inhibitor levels using Nijmegen-Bethesda assays.

Outcome measures

Outcome measures
Measure	High Dose n=1 Participants 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.
Immune Response to FIX	0 BU/mL

SECONDARY outcome

Timeframe: From baseline through week 20 after SB-FIX infusion

Population: All subjects in this study who received any portion of the SB-FIX infusion

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.

Outcome measures

Outcome measures
Measure	High Dose n=1 Participants 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.
Presence of Shedding of AAV2/6 Vector DNA (in Copies/10 µL) by PCR in Plasma Plasma: AAV2/6-ZFN42906 at Week 20: <10 copies/10 μL	1 Participants
Presence of Shedding of AAV2/6 Vector DNA (in Copies/10 µL) by PCR in Plasma Plasma: AAV2/6-hF9 at Week 20: <10 copies/10 μL	1 Participants

SECONDARY outcome

Timeframe: From baseline through week 20 after SB-FIX infusion

Population: All subjects in this study who received any portion of the SB-FIX infusion

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.

Outcome measures

Outcome measures
Measure	High Dose n=1 Participants 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.
Presence and Shedding of AAV2/6 Vector DNA (in Copies/100ng) by PCR in Saliva, Stool and Semen Saliva: AAV2/6-ZFN42906 at week12: <10 copies/100ng	1 Participants
Presence and Shedding of AAV2/6 Vector DNA (in Copies/100ng) by PCR in Saliva, Stool and Semen Saliva: AAV2/6-hF9 at week 12: <10 copies/100ng	1 Participants
Presence and Shedding of AAV2/6 Vector DNA (in Copies/100ng) by PCR in Saliva, Stool and Semen Stool: AAV2/6-ZFN42906 at week 12: <10 copies/100ng	1 Participants
Presence and Shedding of AAV2/6 Vector DNA (in Copies/100ng) by PCR in Saliva, Stool and Semen Stool: AAV2/6-hF9 at week 12: <10 copies/100ng	1 Participants
Presence and Shedding of AAV2/6 Vector DNA (in Copies/100ng) by PCR in Saliva, Stool and Semen Semen: AAV2/6-ZFN42906 at week 20: <20 copies/100ng	1 Participants
Presence and Shedding of AAV2/6 Vector DNA (in Copies/100ng) by PCR in Saliva, Stool and Semen Semen: AAV2/6-hF9 at week 20: <20 copies/100ng	1 Participants

SECONDARY outcome

Timeframe: From baseline through week 12 after SB-FIX infusion

Population: All subjects in this study who received any portion of the SB-FIX infusion

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.

Outcome measures

Outcome measures
Measure	High Dose n=1 Participants 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.
Presence and Shedding of AAV2/6 Vector DNA (in Copies/250 µL) by PCR in Urine Urine: AAV2/6-ZFN42906 at Week 12: <10 copies/250 μL	1 Participants
Presence and Shedding of AAV2/6 Vector DNA (in Copies/250 µL) by PCR in Urine Urine: AAV2/6-hF9 at Week 12: <10 copies/250 μL	1 Participants

Adverse Events

High Dose

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	High Dose n=1 participants at risk 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.
Vascular disorders Flushing	100.0% 1/1 • Number of events 1 • Up to 36 months after the SB-FIX infusion
Cardiac disorders Sinus Tachycardia	100.0% 1/1 • Number of events 1 • Up to 36 months after the SB-FIX infusion
General disorders Chills	100.0% 1/1 • Number of events 1 • Up to 36 months after the SB-FIX infusion
Nervous system disorders Headache	100.0% 1/1 • Number of events 1 • Up to 36 months after the SB-FIX infusion
General disorders Pyrexia	100.0% 1/1 • Number of events 1 • Up to 36 months after the SB-FIX infusion

Additional Information

Medical Monitor

Sangamo Therapeutics

Phone: +1 510 307 7266

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER