Human Immunodeficiency Virus
Conditions
Keywords
HIV-1
Brief summary
This is an early phase research study looking at whether an experimental gene transfer, LVsh5/C46 (also known as Cal-1), is safe and if it can protect the immune system from the effects of HIV without the use of antiretroviral drugs. Cal-1 is an experimental gene transfer agent designed to inhibit HIV infection through 2 active parts: 1. Removing a protein named CCR5 from bone marrow and white blood cells 2. Producing a protein named C46 on bone marrow and white blood cells
Detailed description
It is estimated that 33 million individuals are currently infected with HIV. HIV/AIDS is a disease that impairs immune function, primarily by decreasing CD4+ T lymphocytes. The progression can be contained by daily dosing with antiretroviral therapy (ART) but there are side effects that can be treatment limiting, and the development of HIV drug resistance can force the physician to modify the ART regimen. There are no effective vaccines currently available for HIV. LVsh5/C46 (also known as Cal-1) is a dual therapeutic, self-inactivating lentiviral vector that encodes for both a short hairpin RNA against the HIV-1 co-receptor CCR5 (sh5) and a HIV-1 fusion inhibitor, C46 and inhibits two processes required for HIV-1 infection: 1. Binding of the virus to the cellular CCR5 co-receptor and 2. Fusion of the virus with the host cell The rationale is that Cal-1 introduced into hematopoietic progenitor/stem cells (HSPC) and mature CD4+ T lymphocytes will protect these cells and their progeny cells from HIV-1 infection and its pathogenic sequelae. This may provide a continuous means of controlling HIV-1 after a single or infrequent dose(s), thereby decreasing or delaying (partially or completely) the need for antiretroviral drug therapy.
Interventions
DRUGBusulfan
Intravenous busulfan
BIOLOGICALCal-1 modified HSPC
Hematopoietic progenitor/stem cells (HSPC) modified with LVsh5/C46 (Cal-1)
BIOLOGICALCal-1 modified CD4+ T lymphocytes
CD4+ T lymphocytes modified with LVsh5/C46 (Cal-1)
Sponsors
Calimmune, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Prior to any study-related procedures, signed informed consent indicating that they understand the purpose, risks and procedures required for the study and are willing to participate in the study * Individuals aged 18 to 65 years of age (inclusive) at time of consent * Documented HIV-1 infection ≥ 6 months prior to Screening 1 * Previous treatment with antiretroviral agents that had a demonstrated suppressive effect (defined as plasma HIV RNA ≤ 50 copies/ml) * A documented viable ART regimen option, as determined by the Investigator, taking into account prior ART experience and HIV geno/phenotyping analyses * Not taking antiretroviral therapy for ≥ 6 weeks prior to Screening 1, for one or more of the following reasons: i) Concerns over short-term or long-term toxicities associated with antiretroviral agents, or ii) Treatment fatigue from the daily regimen of life-long therapy * Plasma HIV-1 viral RNA ≥ 5,000 copies/mL and ≤ 100,000 copies/ml at Screening 1 and Screening 2 * CD4+ T lymphocyte count ≥ 500 cells/µl at Screening 1 and Screening 2
Exclusion criteria
* Abnormal hematology at Screening 1: Absolute neutrophil count (ANC) \< 1.5 x 109/L, Platelet count \< 100 x 109/L, Hemoglobin \< 10 g/dL * Abnormal biochemistry at Screening 1: Alanine aminotransferase (ALT) \> 2.5 x Upper Limit of Normal (ULN), Total bilirubin \> 1.5 x ULN, Serum creatinine \> 1.5 x ULN * Detection of any CXCR4-tropic HIV-1 at Screening 1 * Evidence of co-infection with hepatitis B virus, hepatitis C virus, West Nile Virus, or HTLV-1 as detected at Screening 2 * Evidence of active TB infection determined by positive QuantiFERON®-TB Gold/IGRA test result and clinical confirmation at Screening 2 * ART or other antiretroviral therapy within 6 weeks of Screening 1 or any time during the pre-infusion period * Documented history of CD4+ T lymphocyte count \< 250 cells/µl * Any previous or current AIDS-defining illnesses (CDC Category C), including AIDS-related dementia, with the exception of Kaposi's sarcoma confined to the skin * History of malignancy or systemic chemotherapy within the last 5 years (i.e., subjects with prior malignancy must be disease-free for 5 years), except curatively-treated basal cell carcinoma, cutaneous squamous cell carcinoma, or cervical or anal intra-epithelial neoplasia * History of steroid-dependent asthma in the past 5 years * History of seizure * Any clinical history of hematologic diseases including leukemia, myelodysplasia, myeloproliferative disease, thromboembolic disease, sickle cell disorder, thrombocytopenia or leukopenia * Class II-IV heart failure, according to the New York Heart Association classification * Inadequate venous access for apheresis, as assessed at Screening 1 * Current or planned systemic immunosuppressive or immunomodulatory medication * Taking warfarin, aspirin or any medication that is likely to affect platelet function or other aspects of blood coagulation, and unable to safely cease this medication for a period of 1 week prior, during, and 1 week after administration of G-CSF (a total period of 19 days) * Participation in any study involving any investigational drug or medical device within 30 days prior to Screening 1 * Receipt of a vaccine for HIV-1 or any gene transfer product at any time * Prior treatment with recombinant G-CSF or busulfan or other stem-cell mobilizing or modulating agent within the previous 12 months * Known hypersensitivity to busulfan, G-CSF (Neupogen™) or E. coli-derived proteins * Subjects who will not accept transfusions of blood products * Pregnant or breast-feeding at any time between Screening 1 and Baseline (infusion) * History of alcohol or drug abuse within the 12 months prior to Screening 1 * Inability to understand and provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Severe and Life-threatening Adverse Events (AEs) | Up to 48 weeks | — |
| Number of Participants With Severe or Life-threatening AEs Related to CSL202 | Up to 48 weeks | — |
| Number of Participants With the Presence of Replication-competent Retrovirus | Up to 48 weeks | — |
| Number of Participants With Predominant Integration Site Analysis | Up to 48 weeks | Vector Integration Site Analysis performed only when Cal-1 Marking is \>= 1%. |
| Mean Cell Dose for CD4+ Cells (Ttn) | Up to 48 weeks | — |
| Mean Cell Dose for CD34+ Cells (HSPCtn) | Up to 48 weeks | — |
| Percent Transduction Efficiency of CD4+ Cells (Ttn) and CD34+ Cells (HSPCtn) of Final Cell Product | Up to 48 weeks | — |
| Total Area Under the Curve (AUC) for Busulfan | Up to 48 weeks | Cohort 3: Total AUC = first dose AUC value + second dose AUC value |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Cal-1 Marking in Peripheral Blood | Up to 48 weeks | — |
| Number of Participants With HIV-1 Tropism Shift | Up to 48 weeks | Shift from R5 to X4 or dual/mixed tropism |
| Cal-1 Marking in Gut-associated Lymphoid Tissue (GALT) (10-15 cm) | Up to 48 weeks | Samples were collected via endoscopic biopsy from the sigmoid colon: 10-15 cm from the anal margin |
| Cal-1 Marking in GALT (25-35 cm) | Up to 48 weeks | Samples were collected via endoscopic biopsy from the sigmoid colon: 25-35 cm from the anal margin |
| Cal-1 Marking in Bone Marrow | Up to 48 weeks | — |
| Cal-1 C46 Expression in Peripheral Blood | Up to 48 weeks | C46 relative expression will be analyzed by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and normalized to the expression of β2-microglobulin (β2M) mRNA |
| Cal-1 sh5 Expression in Peripheral Blood | Up to 48 weeks | sh5 relative expression will be analyzed by RT-qPCR and normalized to the expression of RNU38B microRNA |
| HIV Viral Load at Baseline Screening and Week 48 or at Anti-retroviral Therapy (ART) Re-commencement | Up to 48 weeks | — |
| CD4+ Count at Baseline Screening and Week 48 or at ART Re-commencement | Up to 48 weeks | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (CSL202 With No Busulfan) Cal-1 modified HSPC and Cal-1 modified CD4+ T lymphocytes (CSL202) without busulfan preconditioning | 4 |
| Cohort 2 (CSL202 With 1 Busulfan Dose) Cal-1 modified HSPC and Cal-1 modified CD4+ T lymphocytes (CSL202), with single 4mg/kg busulfan dose administered as pre-conditioning for transplant
Busulfan: Intravenous busulfan | 4 |
| Cohort 3 (CSL202 With 2 Busulfan Doses) Cal-1 modified HSPC and Cal-1 modified CD4+ T lymphocytes (CSL202), first busulfan dose = 3mg/kg and second busulfan dose adjusted (total target exposure of 8,000 μmolar/min AUC)administered as pre-conditioning for transplant
Busulfan: Intravenous busulfan | 5 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Continued to Week 48 but recommenced ART | 3 | 2 | 3 |
| Overall Study | Not infused due to manufacturing failure | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 2 (CSL202 With 1 Busulfan Dose) | Cohort 3 (CSL202 With 2 Busulfan Doses) | Total | Cohort 1 (CSL202 With No Busulfan) |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 5 Participants | 13 Participants | 4 Participants |
| Age, Continuous | 48.5 years STANDARD_DEVIATION 12.8 | 46.8 years STANDARD_DEVIATION 3.1 | 46.2 years STANDARD_DEVIATION 9.2 | 43.0 years STANDARD_DEVIATION 11.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 5 Participants | 12 Participants | 4 Participants |
| Region of Enrollment United States | 4 participants | 5 participants | 13 participants | 4 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 13 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 | 0 / 5 |
| other Total, other adverse events | 4 / 4 | 4 / 4 | 5 / 5 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 1 / 5 |
Outcome results
Primary
Mean Cell Dose for CD34+ Cells (HSPCtn)
Time frame: Up to 48 weeks
Population: SP (1 participant in Cohort 3 withdrew consent and did not receive busulfan or Ttn and HSPCtn)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1 (CSL202 With No Busulfan) | Mean Cell Dose for CD34+ Cells (HSPCtn) | 2.1 Number (10^6 cells/kg body weight) |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Mean Cell Dose for CD34+ Cells (HSPCtn) | 2.4 Number (10^6 cells/kg body weight) |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Mean Cell Dose for CD34+ Cells (HSPCtn) | 10.6 Number (10^6 cells/kg body weight) |
Primary
Mean Cell Dose for CD4+ Cells (Ttn)
Time frame: Up to 48 weeks
Population: SP (1 participant in Cohort 3 withdrew consent and did not receive busulfan or Ttn and HSPCtn)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1 (CSL202 With No Busulfan) | Mean Cell Dose for CD4+ Cells (Ttn) | 16.940 Number (10^8 cells) |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Mean Cell Dose for CD4+ Cells (Ttn) | 81.855 Number (10^8 cells) |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Mean Cell Dose for CD4+ Cells (Ttn) | 49.553 Number (10^8 cells) |
Primary
Number of Participants With Predominant Integration Site Analysis
Vector Integration Site Analysis performed only when Cal-1 Marking is \>= 1%.
Time frame: Up to 48 weeks
Population: SP (1 participant in Cohort 3 withdrew consent and did not receive busulfan or Ttn and HSPCtn)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 (CSL202 With No Busulfan) | Number of Participants With Predominant Integration Site Analysis | NA Participants |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Number of Participants With Predominant Integration Site Analysis | NA Participants |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Number of Participants With Predominant Integration Site Analysis | NA Participants |
Primary
Number of Participants With Severe and Life-threatening Adverse Events (AEs)
Time frame: Up to 48 weeks
Population: Safety Population (SP): The safety population includes all enrolled subjects signing informed consent who started the interventional phase of the trial (i.e. CD4+ Apheresis and discontinued subjects who re-commenced ART)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 (CSL202 With No Busulfan) | Number of Participants With Severe and Life-threatening Adverse Events (AEs) | Severe | 0 Participants |
| Cohort 1 (CSL202 With No Busulfan) | Number of Participants With Severe and Life-threatening Adverse Events (AEs) | Life-threatening | 0 Participants |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Number of Participants With Severe and Life-threatening Adverse Events (AEs) | Severe | 4 Participants |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Number of Participants With Severe and Life-threatening Adverse Events (AEs) | Life-threatening | 3 Participants |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Number of Participants With Severe and Life-threatening Adverse Events (AEs) | Severe | 4 Participants |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Number of Participants With Severe and Life-threatening Adverse Events (AEs) | Life-threatening | 4 Participants |
Primary
Number of Participants With Severe or Life-threatening AEs Related to CSL202
Time frame: Up to 48 weeks
Population: SP
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 (CSL202 With No Busulfan) | Number of Participants With Severe or Life-threatening AEs Related to CSL202 | 0 Participants |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Number of Participants With Severe or Life-threatening AEs Related to CSL202 | 0 Participants |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Number of Participants With Severe or Life-threatening AEs Related to CSL202 | 1 Participants |
Primary
Number of Participants With the Presence of Replication-competent Retrovirus
Time frame: Up to 48 weeks
Population: SP
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 (CSL202 With No Busulfan) | Number of Participants With the Presence of Replication-competent Retrovirus | 0 Participants |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Number of Participants With the Presence of Replication-competent Retrovirus | 0 Participants |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Number of Participants With the Presence of Replication-competent Retrovirus | 0 Participants |
Primary
Percent Transduction Efficiency of CD4+ Cells (Ttn) and CD34+ Cells (HSPCtn) of Final Cell Product
Time frame: Up to 48 weeks
Population: SP (1 participant in Cohort 3 withdrew consent and did not receive busulfan or Ttn and HSPCtn)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1 (CSL202 With No Busulfan) | Percent Transduction Efficiency of CD4+ Cells (Ttn) and CD34+ Cells (HSPCtn) of Final Cell Product | CD4+ Cells (Ttn) | 41.0 Percent transduction efficiency |
| Cohort 1 (CSL202 With No Busulfan) | Percent Transduction Efficiency of CD4+ Cells (Ttn) and CD34+ Cells (HSPCtn) of Final Cell Product | CD34+ Cells (HSPCtn) | 58.6 Percent transduction efficiency |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Percent Transduction Efficiency of CD4+ Cells (Ttn) and CD34+ Cells (HSPCtn) of Final Cell Product | CD4+ Cells (Ttn) | 29.2 Percent transduction efficiency |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Percent Transduction Efficiency of CD4+ Cells (Ttn) and CD34+ Cells (HSPCtn) of Final Cell Product | CD34+ Cells (HSPCtn) | 26.3 Percent transduction efficiency |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Percent Transduction Efficiency of CD4+ Cells (Ttn) and CD34+ Cells (HSPCtn) of Final Cell Product | CD4+ Cells (Ttn) | 66.8 Percent transduction efficiency |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Percent Transduction Efficiency of CD4+ Cells (Ttn) and CD34+ Cells (HSPCtn) of Final Cell Product | CD34+ Cells (HSPCtn) | 31.3 Percent transduction efficiency |
Primary
Total Area Under the Curve (AUC) for Busulfan
Cohort 3: Total AUC = first dose AUC value + second dose AUC value
Time frame: Up to 48 weeks
Population: SP (1 participant in Cohort 3 withdrew consent and did not receive busulfan or Ttn and HSPCtn)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1 (CSL202 With No Busulfan) | Total Area Under the Curve (AUC) for Busulfan | 6521.5 micromolar*min |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Total Area Under the Curve (AUC) for Busulfan | 8296.8 micromolar*min |
Secondary
Cal-1 C46 Expression in Peripheral Blood
C46 relative expression will be analyzed by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and normalized to the expression of β2-microglobulin (β2M) mRNA
Time frame: Up to 48 weeks
Population: SP (1 participant in Cohort 3 withdrew consent and did not receive busulfan or Ttn and HSPCtn)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1 (CSL202 With No Busulfan) | Cal-1 C46 Expression in Peripheral Blood | Peak marking | 0.0000 units of relative expression |
| Cohort 1 (CSL202 With No Busulfan) | Cal-1 C46 Expression in Peripheral Blood | Week 48 | 0.0000 units of relative expression |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Cal-1 C46 Expression in Peripheral Blood | Peak marking | 1.0496 units of relative expression |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Cal-1 C46 Expression in Peripheral Blood | Week 48 | 0.0000 units of relative expression |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Cal-1 C46 Expression in Peripheral Blood | Peak marking | 2.1701 units of relative expression |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Cal-1 C46 Expression in Peripheral Blood | Week 48 | 0.0000 units of relative expression |
Secondary
Cal-1 Marking in Bone Marrow
Time frame: Up to 48 weeks
Population: SP (1 participant in Cohort 3 withdrew consent and did not receive busulfan or Ttn and HSPCtn)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1 (CSL202 With No Busulfan) | Cal-1 Marking in Bone Marrow | Peak marking | 0.0007 copies/cell |
| Cohort 1 (CSL202 With No Busulfan) | Cal-1 Marking in Bone Marrow | Week 48 | 0.0007 copies/cell |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Cal-1 Marking in Bone Marrow | Peak marking | 0.0539 copies/cell |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Cal-1 Marking in Bone Marrow | Week 48 | 0.0015 copies/cell |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Cal-1 Marking in Bone Marrow | Peak marking | 0.0021 copies/cell |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Cal-1 Marking in Bone Marrow | Week 48 | 0.0009 copies/cell |
Secondary
Cal-1 Marking in GALT (25-35 cm)
Samples were collected via endoscopic biopsy from the sigmoid colon: 25-35 cm from the anal margin
Time frame: Up to 48 weeks
Population: SP (1 participant in Cohort 3 withdrew consent and did not receive busulfan or Ttn and HSPCtn)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1 (CSL202 With No Busulfan) | Cal-1 Marking in GALT (25-35 cm) | Peak marking | 0.0255 copies/cell |
| Cohort 1 (CSL202 With No Busulfan) | Cal-1 Marking in GALT (25-35 cm) | Week 48 | 0.0255 copies/cell |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Cal-1 Marking in GALT (25-35 cm) | Peak marking | 0.0003 copies/cell |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Cal-1 Marking in GALT (25-35 cm) | Week 48 | 0.0003 copies/cell |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Cal-1 Marking in GALT (25-35 cm) | Peak marking | 0.0068 copies/cell |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Cal-1 Marking in GALT (25-35 cm) | Week 48 | 0.0055 copies/cell |
Secondary
Cal-1 Marking in Gut-associated Lymphoid Tissue (GALT) (10-15 cm)
Samples were collected via endoscopic biopsy from the sigmoid colon: 10-15 cm from the anal margin
Time frame: Up to 48 weeks
Population: SP (1 participant in Cohort 3 withdrew consent and did not receive busulfan or Ttn and HSPCtn)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1 (CSL202 With No Busulfan) | Cal-1 Marking in Gut-associated Lymphoid Tissue (GALT) (10-15 cm) | Peak marking | 0.8121 copies/cell |
| Cohort 1 (CSL202 With No Busulfan) | Cal-1 Marking in Gut-associated Lymphoid Tissue (GALT) (10-15 cm) | Week 48 | 0.8121 copies/cell |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Cal-1 Marking in Gut-associated Lymphoid Tissue (GALT) (10-15 cm) | Peak marking | 0.0007 copies/cell |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Cal-1 Marking in Gut-associated Lymphoid Tissue (GALT) (10-15 cm) | Week 48 | 0.0004 copies/cell |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Cal-1 Marking in Gut-associated Lymphoid Tissue (GALT) (10-15 cm) | Peak marking | 0.0022 copies/cell |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Cal-1 Marking in Gut-associated Lymphoid Tissue (GALT) (10-15 cm) | Week 48 | 0.0001 copies/cell |
Secondary
Cal-1 sh5 Expression in Peripheral Blood
sh5 relative expression will be analyzed by RT-qPCR and normalized to the expression of RNU38B microRNA
Time frame: Up to 48 weeks
Population: SP (1 participant in Cohort 3 withdrew consent and did not receive busulfan or Ttn and HSPCtn)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1 (CSL202 With No Busulfan) | Cal-1 sh5 Expression in Peripheral Blood | Peak marking | 0.0000 units of relative expression |
| Cohort 1 (CSL202 With No Busulfan) | Cal-1 sh5 Expression in Peripheral Blood | Week 48 | 0.0000 units of relative expression |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Cal-1 sh5 Expression in Peripheral Blood | Peak marking | 0.2027 units of relative expression |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Cal-1 sh5 Expression in Peripheral Blood | Week 48 | 0.0000 units of relative expression |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Cal-1 sh5 Expression in Peripheral Blood | Peak marking | 1.6933 units of relative expression |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Cal-1 sh5 Expression in Peripheral Blood | Week 48 | 0.0000 units of relative expression |
Secondary
CD4+ Count at Baseline Screening and Week 48 or at ART Re-commencement
Time frame: Up to 48 weeks
Population: SP (1 participant in Cohort 3 withdrew consent and did not receive busulfan or Ttn and HSPCtn)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1 (CSL202 With No Busulfan) | CD4+ Count at Baseline Screening and Week 48 or at ART Re-commencement | Baseline screening | 680.75 CD4+ cells/cubic mm |
| Cohort 1 (CSL202 With No Busulfan) | CD4+ Count at Baseline Screening and Week 48 or at ART Re-commencement | Week 48 or at ART re-commencement | 553.3 CD4+ cells/cubic mm |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | CD4+ Count at Baseline Screening and Week 48 or at ART Re-commencement | Baseline screening | 575.13 CD4+ cells/cubic mm |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | CD4+ Count at Baseline Screening and Week 48 or at ART Re-commencement | Week 48 or at ART re-commencement | 383.5 CD4+ cells/cubic mm |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | CD4+ Count at Baseline Screening and Week 48 or at ART Re-commencement | Baseline screening | 668.63 CD4+ cells/cubic mm |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | CD4+ Count at Baseline Screening and Week 48 or at ART Re-commencement | Week 48 or at ART re-commencement | 245.5 CD4+ cells/cubic mm |
Secondary
HIV Viral Load at Baseline Screening and Week 48 or at Anti-retroviral Therapy (ART) Re-commencement
Time frame: Up to 48 weeks
Population: SP (1 participant in Cohort 3 withdrew consent and did not receive busulfan or Ttn and HSPCtn)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1 (CSL202 With No Busulfan) | HIV Viral Load at Baseline Screening and Week 48 or at Anti-retroviral Therapy (ART) Re-commencement | Baseline screening | 4.59 Log10 (copies/mL) |
| Cohort 1 (CSL202 With No Busulfan) | HIV Viral Load at Baseline Screening and Week 48 or at Anti-retroviral Therapy (ART) Re-commencement | Week 48 or at ART re-commencement | 4.56 Log10 (copies/mL) |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | HIV Viral Load at Baseline Screening and Week 48 or at Anti-retroviral Therapy (ART) Re-commencement | Baseline screening | 4.51 Log10 (copies/mL) |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | HIV Viral Load at Baseline Screening and Week 48 or at Anti-retroviral Therapy (ART) Re-commencement | Week 48 or at ART re-commencement | 4.70 Log10 (copies/mL) |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | HIV Viral Load at Baseline Screening and Week 48 or at Anti-retroviral Therapy (ART) Re-commencement | Baseline screening | 4.28 Log10 (copies/mL) |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | HIV Viral Load at Baseline Screening and Week 48 or at Anti-retroviral Therapy (ART) Re-commencement | Week 48 or at ART re-commencement | 4.61 Log10 (copies/mL) |
Secondary
Number of Participants With HIV-1 Tropism Shift
Shift from R5 to X4 or dual/mixed tropism
Time frame: Up to 48 weeks
Population: SP
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 (CSL202 With No Busulfan) | Number of Participants With HIV-1 Tropism Shift | 0 Participants |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Number of Participants With HIV-1 Tropism Shift | 0 Participants |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Number of Participants With HIV-1 Tropism Shift | 0 Participants |
Secondary
Percent Cal-1 Marking in Peripheral Blood
Time frame: Up to 48 weeks
Population: SP (1 participant in Cohort 3 withdrew consent and did not receive busulfan or Ttn and HSPCtn)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1 (CSL202 With No Busulfan) | Percent Cal-1 Marking in Peripheral Blood | Peak marking | 0.3500 percent Cal-1 marking |
| Cohort 1 (CSL202 With No Busulfan) | Percent Cal-1 Marking in Peripheral Blood | Week 48 | 0.0000 percent Cal-1 marking |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Percent Cal-1 Marking in Peripheral Blood | Peak marking | 0.7650 percent Cal-1 marking |
| Cohort 2 (CSL202 With 1 Busulfan Dose) | Percent Cal-1 Marking in Peripheral Blood | Week 48 | 0.1275 percent Cal-1 marking |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Percent Cal-1 Marking in Peripheral Blood | Peak marking | 3.1200 percent Cal-1 marking |
| Cohort 3 (CSL202 With 2 Busulfan Doses) | Percent Cal-1 Marking in Peripheral Blood | Week 48 | 0.1275 percent Cal-1 marking |