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The purpose of the study is to evaluate the safety, tolerability and effect on HIV viral load, of escalating doses of cyclophosphamide administered 1 day prior to SB-728-T infusion.
The objectives of the study are to augment HIV-specific T-cells and to reverse or decrease the progressive destruction of CD4+ T-cells that leads to clinical AIDS. Levels of engraftment vary from negligible to about 10% of the CD4+ T-cells in the vascular compartment. Preliminary analyses of HAART TI suggest that an anti-HIV effect may correlate with the level of SB-728-T engraftment. Concurrently, non-myeloablative lymphodepletion with cyclophosphamide has been demonstrated to enhance engraftment of adoptively transferred T-cells through a variety of mechanisms. The study is being undertaken to increase SB-728-T engraftment through the administration of low non-myeloablative doses of cyclophosphamide.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 - IV cyclophosphamide 200 mg | Experimental |
| |
| Cohort 2 - IV cyclophosphamide 0.5 g/m2 | Experimental |
| |
| Cohort 3 - IV cyclophosphamide 1.0 g/m2 | Experimental |
| |
| Cohort 4 - IV cyclophosphamide 2.0 g/m2 | Experimental |
| |
| Cohort 5 - IV cyclophosphamide 1.5 g/m2 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SB-728-T | Genetic | Infusion will be 5 to 30 billion ZFN modified CD4+ T cells 1 day following IV cyclophosphamide 200 mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Treatment-emergent Adverse Events | Number of Participants with Treatment related Adverse Events in subjects who received any portion of the SB-728-T infusion | 28 days after the SB-728-T infusion of the last subject in each Cohort and up to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of Escalating Doses of Cyclophosphamide on SB-728-T Engraftment as Measured by CCR5 Modified CD4 Cells in Blood. | Effect of repeat doses of SB-728-T on engraftment following cyclophosphamide conditioning as measured by CCR5 Modified CD4 Cells in blood at Month 12. | Up to 12 months after the last SB-728-T infusion |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCLA Care Center | Los Angeles | California | 90035 | United States | ||
| Quest Clinical Research |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 - IV Cyclophosphamide 200 mg | SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells 1 day following IV cyclophosphamide 200 mg |
| FG001 | Cohort 2 - IV Cyclophosphamide 0.5 g/m2 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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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 | Jan 30, 2014 | Mar 12, 2021 |
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| SB-728-T | Genetic | Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 0.5 g/m2 |
|
|
| SB-728-T | Genetic | Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 1.0 g/m2 |
|
|
| SB-728-T | Genetic | Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 2.0 g/m2 |
|
|
| SB-728-T | Genetic | Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 1.5 g/m2 |
|
|
| Effect of SB-728-T on Plasma HIV-1 RNA Levels Following HAART Interruption |
Effect of SB-728-T on plasma HIV-1 RNA levels following HAART interruption. The unit is log copies/mL, except for the Cohort 1, the unit is " copies/mL". Cohort 1 mean and SD are 0. All 3 subjects had NO HIV-1 RNA DETECTED. |
| Up to 12 months after the last SB-728-T infusion |
| Change From Baseline to Month 12 in CD4+ T-cell Counts in Peripheral Blood After Repeat Treatments With SB-728-T. (i.e. Month 12 Value - Baseline Value) | Change from baseline to month 12 in CD4+ T-cell counts in peripheral blood after repeat treatments with SB-728-T. (i.e. month 12 value - baseline value) | Up to 12 months after the last SB-728-T infusion |
| San Francisco |
| California |
| 94115 |
| United States |
| Circle CARE Center, LLC | Norwalk | Connecticut | 06850 | United States |
| Orlando Immunology Center | Orlando | Florida | 32803 | United States |
| Central West Clinical Research, Inc. | St Louis | Missouri | 63108 | United States |
| Southwest CARE Center | Santa Fe | New Mexico | 87505 | United States |
| Ricky K Hsu, MD, PC | New York | New York | 10011 | United States |
| Central Texas Clinical Research | Austin | Texas | 78705 | United States |
| North Texas Infectious Diseases Consultants | Dallas | Texas | 75246 | United States |
| Gordon Crofoot, MD, PA | Houston | Texas | 77098 | United States |
| Clinical Research Puerto Rico | San Juan | 00909 | Puerto Rico |
SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 0.5 g/m2
| FG002 | Cohort 3 - IV Cyclophosphamide 1.0 g/m2 | SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 1.0 g/m2 |
| FG003 | Cohort 4 - IV Cyclophosphamide 2.0 g/m2 | SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 2.0 g/m2 |
| FG004 | Cohort 5 - IV Cyclophosphamide 1.5 g/m2 | SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 1.5 g/m2 |
| COMPLETED |
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| NOT COMPLETED |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 - IV Cyclophosphamide 200 mg | SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells 1 day following IV cyclophosphamide 200 mg |
| BG001 | Cohort 2 - IV Cyclophosphamide 0.5 g/m2 | SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 0.5 g/m2 |
| BG002 | Cohort 3 - IV Cyclophosphamide 1.0 g/m2 | SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 1.0 g/m2 |
| BG003 | Cohort 4 - IV Cyclophosphamide 2.0 g/m2 | SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 2.0 g/m2 |
| BG004 | Cohort 5 - IV Cyclophosphamide 1.5 g/m2 | SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 1.5 g/m2 |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| 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 | Treatment-emergent Adverse Events | Number of Participants with Treatment related Adverse Events in subjects who received any portion of the SB-728-T infusion | Posted | Number | participants | 28 days after the SB-728-T infusion of the last subject in each Cohort and up to 12 months |
|
|
| |||||||||||||||||||||||||||||||||||||||
| Secondary | Effect of Escalating Doses of Cyclophosphamide on SB-728-T Engraftment as Measured by CCR5 Modified CD4 Cells in Blood. | Effect of repeat doses of SB-728-T on engraftment following cyclophosphamide conditioning as measured by CCR5 Modified CD4 Cells in blood at Month 12. | Safety Analysis Set | Posted | Mean | Standard Deviation | cells 10^9/L | Up to 12 months after the last SB-728-T infusion |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | Effect of SB-728-T on Plasma HIV-1 RNA Levels Following HAART Interruption | Effect of SB-728-T on plasma HIV-1 RNA levels following HAART interruption. The unit is log copies/mL, except for the Cohort 1, the unit is " copies/mL". Cohort 1 mean and SD are 0. All 3 subjects had NO HIV-1 RNA DETECTED. | Safety Analysis Set | Posted | Mean | Standard Deviation | log copies/mL | Up to 12 months after the last SB-728-T infusion |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline to Month 12 in CD4+ T-cell Counts in Peripheral Blood After Repeat Treatments With SB-728-T. (i.e. Month 12 Value - Baseline Value) | Change from baseline to month 12 in CD4+ T-cell counts in peripheral blood after repeat treatments with SB-728-T. (i.e. month 12 value - baseline value) | Safety Analysis Set | Posted | Mean | Standard Deviation | cells 10^9/L | Up to 12 months after the last SB-728-T infusion |
|
1 year
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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 | Cohort 1 - IV Cyclophosphamide 200 mg | SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells 1 day following IV cyclophosphamide 200 mg | 0 | 3 | 1 | 3 | 3 | 3 |
| EG001 | Cohort 2 - IV Cyclophosphamide 0.5 g/m2 | SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 0.5 g/m2 | 0 | 6 | 0 | 6 | 6 | 6 |
| EG002 | Cohort 3 - IV Cyclophosphamide 1.0 g/m2 | SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 1.0 g/m2 | 0 | 11 | 0 | 11 | 11 | 11 |
| EG003 | Cohort 4 - IV Cyclophosphamide 2.0 g/m2 | SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 2.0 g/m2 | 0 | 3 | 1 | 3 | 3 | 3 |
| EG004 | Cohort 5 - IV Cyclophosphamide 1.5 g/m2 | SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 1.5 g/m2 | 0 | 3 | 0 | 3 | 3 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cellulitis staphylococcal | Infections and infestations | Systematic Assessment |
| ||
| Substance abuse | Psychiatric disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
| ||
| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Abdominal discomfort | Gastrointestinal disorders | Systematic Assessment |
| ||
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| Anal skin tags | Gastrointestinal disorders | Systematic Assessment |
| ||
| Aphthous stomatitis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Constipation | Gastrointestinal disorders | Systematic Assessment |
| ||
| Flatulence | Gastrointestinal disorders | Systematic Assessment |
| ||
| Chills | General disorders | Systematic Assessment |
| ||
| Pyrexia | General disorders | Systematic Assessment |
| ||
| Fatigue | General disorders | Systematic Assessment |
| ||
| Pain | General disorders | Systematic Assessment |
| ||
| Asthenia | General disorders | Systematic Assessment |
| ||
| Malaise | General disorders | Systematic Assessment |
| ||
| Chest pain | General disorders | Systematic Assessment |
| ||
| Temperature intolerance | General disorders | Systematic Assessment |
| ||
| Hepatotoxicity | Hepatobiliary disorders | Systematic Assessment |
| ||
| Food allergy | Immune system disorders | Systematic Assessment |
| ||
| Seasonal allergy | Immune system disorders | Systematic Assessment |
| ||
| Upper respiratory tract infection | Infections and infestations | Systematic Assessment |
| ||
| Sinusitis | Infections and infestations | Systematic Assessment |
| ||
| Furuncle | Infections and infestations | Systematic Assessment |
| ||
| Nasopharyngitis | Infections and infestations | Systematic Assessment |
| ||
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Lymphadenopathy | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Tinnitus | Ear and labyrinth disorders | Systematic Assessment |
| ||
| Hypogonadism | Endocrine disorders | Systematic Assessment |
| ||
| Scintillating scotoma | Eye disorders | Systematic Assessment |
| ||
| Vision blurred | Eye disorders | Systematic Assessment |
| ||
| Balanitis candida | Infections and infestations | Systematic Assessment |
| ||
| Bronchitis | Infections and infestations | Systematic Assessment |
| ||
| Cellulitis staphylococcal | Infections and infestations | Systematic Assessment |
| ||
| Chlamydial infection | Infections and infestations | Systematic Assessment |
| ||
| Fungal skin infection | Infections and infestations | Systematic Assessment |
| ||
| Gonorrhoea | Infections and infestations | Systematic Assessment |
| ||
| Influenza | Infections and infestations | Systematic Assessment |
| ||
| Laryngitis | Infections and infestations | Systematic Assessment |
| ||
| Paronychia | Infections and infestations | Systematic Assessment |
| ||
| Pharyngitis streptococcal | Infections and infestations | Systematic Assessment |
| ||
| Syphilis | Infections and infestations | Systematic Assessment |
| ||
| Tinea pedis | Infections and infestations | Systematic Assessment |
| ||
| Urinary tract infection | Infections and infestations | Systematic Assessment |
| ||
| Exposure to communicable disease | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Laceration | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Muscle strain | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Procedural pain | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Alanine aminotransferase increased | Investigations | Systematic Assessment |
| ||
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
| ||
| Blood phosphorus decreased | Investigations | Systematic Assessment |
| ||
| Blood pressure decreased | Investigations | Systematic Assessment |
| ||
| Decreased appetite | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypertriglyceridaemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hyponatraemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Bone pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Muscle spasms | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Neck pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Anogenital warts | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Fibrous histiocytoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Nervous system disorder | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Headache | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Migraine | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Dizziness | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Psychiatric disorders | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Agitation | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Insomnia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Substance abuse | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Urinary hesitation | Renal and urinary disorders | Systematic Assessment |
| ||
| Respiratory, thoracic and mediastinal disorders | Renal and urinary disorders | Systematic Assessment |
| ||
| Cough | Renal and urinary disorders | Systematic Assessment |
| ||
| Sinus congestion | Renal and urinary disorders | Systematic Assessment |
| ||
| Oropharyngeal pain | Renal and urinary disorders | Systematic Assessment |
| ||
| Respiratory tract congestion | Renal and urinary disorders | Systematic Assessment |
| ||
| Skin odour abnormal | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Hyperhidrosis | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Night sweats | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Acne | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Actinic keratosis | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Alopecia areata | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Dry skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Hair colour changes | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Pityriasis rubra pilaris | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Pruritus generalised | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Hypertension | Vascular disorders | Systematic Assessment |
| ||
| Pallor | Vascular disorders | Systematic Assessment |
| ||
| Venous thrombosis | Vascular disorders | Systematic Assessment |
|
All proposed written materials related to the study or an outline of any proposed oral presentations, shall be submitted to Sangamo for approval at least 45 days prior to submission of materials for publication or any oral disclosure to a third party. If Sangamo determines that a description of patentable subject matter is contained in such written material or outline, it shall notify the clinical site within 1 month after receipt and Sangamo will have an additional 90 days for review.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Monitor | Sangamo Therapeutics | 510-970-6000 | clinicaltrials@sangamo.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 23, 2020 | Mar 12, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
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| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 2.0 g/m2
| OG004 | Cohort 5 - IV Cyclophosphamide 1.5 g/m2 | SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 1.5 g/m2 |
|
|
SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 2.0 g/m2
| OG004 | Cohort 5 - IV Cyclophosphamide 1.5 g/m2 | SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 1.5 g/m2 |
|
|
SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 2.0 g/m2
| OG004 | Cohort 5 - IV Cyclophosphamide 1.5 g/m2 | SB-728-T: Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 1.5 g/m2 |
|
|