ADA-SCID
Conditions
Keywords
gene therapy, hematopoietic stem cell, ADA-SCID, lentiviral vector
Brief summary
The aim of this study is to assess the safety and efficacy of autologous transplantation of hematopoietic stem cells (CD34+ cells) from the bone marrow (BM) of ADA-deficient SCID infants and children following human ADA cDNA transfer by the EFS-ADA lentiviral vector. The level of gene transfer in blood cells and immune function will be measured as endpoints.
Detailed description
The study is open to twenty (20) infants and children diagnosed with ADA-deficient SCID who did not have a medically eligible, human leukocyte antigen (HLA)-identical sibling donor for bone marrow transplantation. The EFS-ADA lentiviral vector with the human ADA cDNA will be used to transduce autologous CD34+ cells from the bone marrow of these subjects. The subjects will receive 4 mg/kg busulfan prior to re-infusion of their gene-modified cells. Safety is the primary endpoint. During the follow-up phase, the investigators aim to determine whether the cells could engraft and produce mature cells that contain and express the corrected ADA gene in the absence of pegademase bovine (PEG-ADA) enzyme replacement therapy (ERT), which will be withheld at Day +30 following transplant. Efficacy studies to evaluate the level of immune reconstitution, will be performed in the first and second years of the study.
Interventions
GENETICInfusion of autologous EFS-ADA LV CD34+ (OTL-101)
autologous EFS-ADA LV CD34+ cells (OTL-101) are infused intravenously
DRUGbusulfan
Busulfan is used for non-myeloablative conditioning
DRUGPEG-ADA ERT
PEG-ADA ERT is discontinued at Day +30 (-3/+15 days) after successful engraftment
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
National Human Genome Research Institute (NHGRI)
National Heart, Lung, and Blood Institute (NHLBI)
Orchard Therapeutics
University of California, Los Angeles
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 17 Years
Healthy volunteers
No
Inclusion criteria
-Children ≥ 1.0 months of age with a diagnosis of ADA-deficient SCID based on A. Decreased ADA enzymatic activity in erythrocytes, leukocytes, skin fibroblasts, or in cultured fetal cells to levels consistent with ADA-deficient SCID as determined by reference laboratory or confirmed ADA gene mutation(s) known to cause disease , AND B. Evidence of severe combined immunodeficiency based on either: 1. Family history of first order relative with ADA deficiency and clinical and laboratory evidence of severe immunologic deficiency, OR 2. Evidence of severe immunologic deficiency in subject prior to institution of immune restorative therapy, based on 1. lymphopenia (absolute lymphocyte count \<400 cells/mcL) OR absence or low number of T cells (absolute CD3+ count \<300 cells/mcL) OR 2. severely decreased T lymphocyte blastogenic responses to phytohemagglutinin (either \<10% of lower limit of normal controls for the diagnostic laboratory, \<10% of the response of the normal control of the day, or stimulation index \<10) * Ineligible for matched sibling allogeneic bone marrow transplantation: absence of a medically eligible HLA-identical sibling, with normal immune function, who may serve as an allogeneic bone marrow donor * Signed written informed consent according to guidelines of the Institutional Review Board (IRB) (UCLA Office of Human Research Protection Program and National Human Genome Research Institute (NHGRI) IRB
Exclusion criteria
1. Age ≤ 1.0 months Appropriate organ function as outlined below must be observed within 60 days of entering this trial. 2. Hematologic 1. Anemia (hemoglobin \< 10.5 g/dl at \< 2 years of age, or \< 11.5 g/dl at \> 2 years of age). 2. Neutropenia (absolute granulocyte count \<500/mm3. 3. Thrombocytopenia (platelet count \< 150,000/mm3, at any age). 4. International Normalised Ratio (INR) or Prothrombin Time (PT) \> 2 times the upper limits of normal or Partial Thromboplastin Time (PTT) \> 2.33 times the upper limit of normal (patients with a correctable deficiency controlled on medication will not be excluded). 5. Cytogenetic abnormalities on peripheral blood or bone marrow or amniotic fluid (if available). 6. Prior allogeneic Hematopoietic Stem Cell Transplant (HSCT) with cytoreductive conditioning 3. Infectious a. Evidence of infection with HIV-1, hepatitis B, Hepatitis C, or parvovirus B 19 by DNA Polymerase Chain Reaction (PCR) within 90 days prior to bone marrow harvest. If other infection is present, it must be under control (e.g. stable or decreasing viral load) at the time of screening 4. Pulmonary 1. Resting O2 saturation by pulse oximetry \< 95% on room air. 2. Chest x-ray indicating active or progressive pulmonary disease. 5. Cardiac 1. Abnormal electrocardiogram (EKG) indicating cardiac pathology. 2. Uncorrected congenital cardiac malformation with clinical symptomatology. 3. Active cardiac disease, including clinical evidence of congestive heart failure, cyanosis, hypotension. 4. Poor cardiac function as evidenced by LV ejection fraction \< 40% on echocardiogram. 6. Neurologic 1. Significant neurologic abnormality by examination. 2. Uncontrolled seizure disorder. 7. Renal 1. Renal insufficiency: serum creatinine \>= 1.2 mg/dl, or \>= 3+ proteinuria. 2. Abnormal serum sodium, potassium, calcium, magnesium, phosphate at grade III or IV by Division of AIDS Toxicity Scale. 8. Hepatic/GI: 1. Serum transaminases \> 5 times the upper limit of normal (ULN). 2. Serum bilirubin \> 2 times ULN. 3. Serum glucose \> 1.5 times ULN. 4. Intractable severe diarrhea. 9. Oncologic 1. Evidence of active malignant disease other than dermatofibrosarcoma protuberans (DFSP) 2. Evidence of DFSP expected to require anti-neoplastic therapy within the 5 years following the infusion of genetically corrected cells 3. Evidence of DFSP expected to be life limiting within the 5 years following the infusion of genetically corrected cells 10. Known sensitivity to Busulfan 11. General 1. Expected survival \< 6 months. 2. Pregnant. 3. Major congenital anomaly. 4. Ineligible for autologous HSCT by the criteria at the clinical site. 5. Other conditions which in the opinion of the principal investigator and/or co-investigators, contra-indicate the bone marrow harvest, the administration of busulfan, infusion of transduced cells or indicate the patient or patient's parents/primary caregivers inability to follow protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 12 months | Overall survival is defined as the percentage of subjects alive at 12 months post- treatment with OTL-101 or HSCT |
| Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 12 months | Event-free survival is defined as the percentage of subjects alive with no event, an event being the resumption of PEG-ADA ERT or the need for a rescue allogeneic Hematopoietic Stem Cell Transplant (HSCT), or death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vector Copy Number (VCN) in Peripheral Blood (PB) Granulocytes. | 24 months | Vector copy number in the PB granulocyte fraction that was T cell depleted, is a surrogate for amount of engrafted genetically modified Hematopoietic stem cell (HSC) that are producing granulocytes every 3-5 days. VCN analysis was performed by Droplet Digital PCR (ddPCR) on DNA extracted from peripheral blood granulocytes. |
| VCN in Peripheral Blood Mononuclear Cells (PBMCs) | 24 months | PBMC VCN is a measure of the accumulation of peripheral blood leukocytes arising from engrafted, genetically modified HSC. VCN analysis was performed by ddPCR on DNA extracted from PBMC. |
| ADA Activity in Erythrocytes | 24 months | ADA enzyme activity measured to assess the amount of functional gene product produced from the normal ADA transgene delivered by EFS-ADA LV; persistence of ADA enzyme activity over time demonstrates successful engraftment and differentiation of genetically modified HSC. |
| OS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years) | 24 months | OS is defined as the percentage of subjects alive at 24 months post- treatment with OTL-101 or HSCT |
| Change From Baseline in CD3+ T Cell Counts (2 Years) | 24 months | Immune reconstitution was assessed by change in CD3+ T Cell counts at baseline to Month 24. |
| Number of Single Integration Sites Representing >30% of the Total Integration Sites (2 Years) | 24 months | Vector Integration Site Analysis (VISA) allowed determination of the distribution of vector integration sites in each subject's genome, as well as the relative clonal abundance. VISA was to be considered abnormal for a subject if, in 2 or more instances during the course of follow-up, a single integration site was found to represent \>30% of the total integration sites detected. |
| Severe Infection Rate Excluding the First Three Months After Treatment | 24 months | The infections of interest in this study were severe infections or opportunistic infectious episodes, defined as infections requiring hospitalization or prolonging hospitalization and/or documented infections by opportunistic pathogens. Infections that took place in the first 3 months of follow-up post treatment were excluded from calculations to avoid possible bias introduced in the data by the effects of conditioning. |
| Reduction in Deoxyadenosine Nucleotide (dAXP) in Erythrocytes | 24 months | Decreased dAXP levels coincide with increased ADA enzyme activity, detoxification was used to demonstrate functional ADA enzyme production from the introduced ADA transgene. The threshold for detoxification was \<100 μmol/L. |
| EvFS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years) | 24 months | Event-free survival is defined as the percentage of subjects alive with no event, an event being the resumption of PEG-ADA ERT or the need for a rescue allogenic Hematopoietic Stem Cell Transplant (HSCT), or death. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gene Therapy Infusion of autologous CD34+ cells genetically modified by the EF1αS-ADA (EFS-ADA) lentiviral vector (LV)
Busulfan: Busulfan is used for non-myeloablative conditioning
Polyethylene glycol-modified adenosine deaminase (PEG-ADA): PEG-ADA enzyme replacement therapy (ERT) is discontinued at Day 30 +/- 3 days from date of infusion of OTL-101. | 20 |
| Historical Control Group Historical data from patients with Severe Combined Immunodeficiency Due to ADA Deficiency (ADA-SCID) who were treated with Hematopoietic Stem Cell Transplantation (HSCT): Historical data from a database of ADA-SCID patients treated with allogeneic HSCT from Great Ormond Street Hospital (GOSH) and Duke University Children's Hospital were collected as comparator group. | 26 |
| Total | 46 |
Baseline characteristics
| Characteristic | Gene Therapy | Historical Control Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 20 Participants | 26 Participants | 46 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized African American | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic | 6 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized Native American or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 26 Participants | 26 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 10 Participants | 0 Participants | 10 Participants |
| Region of Enrollment United Kingdom | 0 participants | 16 participants | 16 participants |
| Region of Enrollment United States | 20 participants | 10 participants | 30 participants |
| Sex/Gender, Customized Sex, n Female | 11 Participants | 0 Participants | 11 Participants |
| Sex/Gender, Customized Sex, n Male | 9 Participants | 0 Participants | 9 Participants |
| Sex/Gender, Customized Sex, n Not Reported | 0 Participants | 26 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 9 / 20 |
Outcome results
Primary
Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)
Event-free survival is defined as the percentage of subjects alive with no event, an event being the resumption of PEG-ADA ERT or the need for a rescue allogeneic Hematopoietic Stem Cell Transplant (HSCT), or death.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTL-101 Gene Therapy | Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 100 percentage of participants |
| HSCT Controls Without MRD | Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 64.29 percentage of participants |
| HSCT Controls With MRD | Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 100 percentage of participants |
| All HSCT Control Group | Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 80.77 percentage of participants |
Comparison: Percentage of patients with EvFS at 1-year post-treatment in the historical control groups (without MRD) were compared to the percentage of study patients with EvFS at 1-year post-treatment with OTL-101. Results are reported as percentage difference in EvFS of historical control group from OTL-101 on-study subjects.95% CI: [11.21, 64.86]
Comparison: Percentage of patients with EvFS at 1-year post-treatment in the historical control groups (with MRD) were compared to the percentage of study patients with EvFS at 1-year post-treatment with OTL-101. Results are reported as percentage difference in EvFS of historical control group from OTL-101 on-study subjects.
Comparison: Percentage of patients with EvFS at 1-year post-treatment in the historical control groups (all control patients) were compared to the percentage of study patients with EvFS at 1-year post-treatment with OTL-101. Results are reported as percentage difference in EvFS of historical control group from OTL-101 on-study subjects.95% CI: [0.71, 39.35]
Primary
Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)
Overall survival is defined as the percentage of subjects alive at 12 months post- treatment with OTL-101 or HSCT
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTL-101 Gene Therapy | Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 100 percentage of participants |
| HSCT Controls Without MRD | Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 85.71 percentage of participants |
| HSCT Controls With MRD | Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 100 percentage of participants |
| All HSCT Control Group | Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year) | 92.31 percentage of participants |
Comparison: Percentage of patients alive at 1-year post-treatment in the historical control groups (without MRD) were compared to the percentage of study patients alive at 1-year post-treatment with OTL-101. Results are reported as percentage difference in OS of historical control group from OTL-101 on-study subjects.95% CI: [-5.4, 42.81]
Comparison: Percentage of patients alive at 1-year post-treatment in the historical control groups (with MRD) were compared to the percentage of study patients alive at 1-year post-treatment with OTL-101. Results are reported as percentage difference in OS of historical control group from OTL-101 on-study subjects.
Comparison: Percentage of patients alive at 1-year post-treatment in the historical control groups (all control patients) were compared to the percentage of study patients alive at 1-year post-treatment with OTL-101. Results are reported as percentage difference in OS of historical control group from OTL-101 on-study subjects.95% CI: [-10.08, 25.13]
Secondary
ADA Activity in Erythrocytes
ADA enzyme activity measured to assess the amount of functional gene product produced from the normal ADA transgene delivered by EFS-ADA LV; persistence of ADA enzyme activity over time demonstrates successful engraftment and differentiation of genetically modified HSC.
Time frame: 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OTL-101 Gene Therapy | ADA Activity in Erythrocytes | 105.50 nmol/h/mg |
| HSCT Controls Without MRD | ADA Activity in Erythrocytes | 48.500 nmol/h/mg |
| HSCT Controls With MRD | ADA Activity in Erythrocytes | 1.000 nmol/h/mg |
| All HSCT Control Group | ADA Activity in Erythrocytes | 2.000 nmol/h/mg |
Secondary
Change From Baseline in CD3+ T Cell Counts (2 Years)
Immune reconstitution was assessed by change in CD3+ T Cell counts at baseline to Month 24.
Time frame: 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OTL-101 Gene Therapy | Change From Baseline in CD3+ T Cell Counts (2 Years) | 569.0 cells/μL |
| HSCT Controls Without MRD | Change From Baseline in CD3+ T Cell Counts (2 Years) | 340.0 cells/μL |
| HSCT Controls With MRD | Change From Baseline in CD3+ T Cell Counts (2 Years) | 538.0 cells/μL |
| All HSCT Control Group | Change From Baseline in CD3+ T Cell Counts (2 Years) | 395.5 cells/μL |
Secondary
EvFS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years)
Event-free survival is defined as the percentage of subjects alive with no event, an event being the resumption of PEG-ADA ERT or the need for a rescue allogenic Hematopoietic Stem Cell Transplant (HSCT), or death.
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTL-101 Gene Therapy | EvFS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years) | 100 percentage of participants |
| HSCT Controls Without MRD | EvFS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years) | 50.00 percentage of participants |
| HSCT Controls With MRD | EvFS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years) | 63.64 percentage of participants |
| All HSCT Control Group | EvFS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years) | 56.00 percentage of participants |
Comparison: Percentage of patients with EvFS at 2-years post-treatment in the historical control groups (without MRD) were compared to the percentage of study patients with EvFS at 2-years post-treatment with OTL-101. Results are reported as percentage difference in EvFS of historical control group from OTL-101 on-study subjects.95% CI: [22.71, 76.96]
Comparison: Percentage of patients with EvFS at 2-years post-treatment in the historical control groups (with MRD) were compared to the percentage of study patients with EvFS at 2-years post-treatment with OTL-101. Results are reported as percentage difference in EvFS of historical control group from OTL-101 on-study subjects.95% CI: [9.8, 69.21]
Comparison: Percentage of patients with EvFS at 2-years post-treatment in the historical control groups (all control patients) were compared to the percentage of study patients with EvFS at 2-years post-treatment with OTL-101. Results are reported as percentage difference in EvFS of historical control group from OTL-101 on-study subjects.95% CI: [22.78, 65.23]
Secondary
Number of Single Integration Sites Representing >30% of the Total Integration Sites (2 Years)
Vector Integration Site Analysis (VISA) allowed determination of the distribution of vector integration sites in each subject's genome, as well as the relative clonal abundance. VISA was to be considered abnormal for a subject if, in 2 or more instances during the course of follow-up, a single integration site was found to represent \>30% of the total integration sites detected.
Time frame: 24 months
Population: Historical control groups/arms are not included in the analysis population for this outcome measure as these subjects did not receive gene therapy, and so measurement of VISA is not relevant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTL-101 Gene Therapy | Number of Single Integration Sites Representing >30% of the Total Integration Sites (2 Years) | 0 number of participants |
Secondary
OS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years)
OS is defined as the percentage of subjects alive at 24 months post- treatment with OTL-101 or HSCT
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTL-101 Gene Therapy | OS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years) | 100 percentage of participants |
| HSCT Controls Without MRD | OS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years) | 85.71 percentage of participants |
| HSCT Controls With MRD | OS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years) | 90.91 percentage of participants |
| All HSCT Control Group | OS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years) | 88.00 percentage of participants |
Comparison: Percentage of patients alive at 2-years post-treatment in the historical control groups (without MRD) were compared to the percentage of study patients alive at 2-years post-treatment with OTL-101. Results are reported as percentage difference in OS of historical control group from OTL-101 on-study subjects.95% CI: [-5.4, 42.81]
Comparison: Percentage of patients alive at 2-years post-treatment in the historical control groups (with MRD) were compared to the percentage of study patients alive at 2-years post-treatment with OTL-101. Results are reported as percentage difference in OS of historical control group from OTL-101 on-study subjects.95% CI: [-9.55, 41.28]
Comparison: Percentage of patients alive at 2-years post-treatment in the historical control groups (all control patients) were compared to the percentage of study patients alive at 2-years post-treatment with OTL-101. Results are reported as percentage difference in OS of historical control group from OTL-101 on-study subjects.95% CI: [-5.62, 31.22]
Secondary
Reduction in Deoxyadenosine Nucleotide (dAXP) in Erythrocytes
Decreased dAXP levels coincide with increased ADA enzyme activity, detoxification was used to demonstrate functional ADA enzyme production from the introduced ADA transgene. The threshold for detoxification was \<100 μmol/L.
Time frame: 24 months
Population: HSCT Controls With MRD arm is not included in the analysis population for this outcome measure as dAXP data was not reported between 17-30 months post-HSCT for any patients in this arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OTL-101 Gene Therapy | Reduction in Deoxyadenosine Nucleotide (dAXP) in Erythrocytes | 0.0330 umol/mL |
| HSCT Controls Without MRD | Reduction in Deoxyadenosine Nucleotide (dAXP) in Erythrocytes | 0.0360 umol/mL |
| HSCT Controls With MRD | Reduction in Deoxyadenosine Nucleotide (dAXP) in Erythrocytes | 0.0360 umol/mL |
Secondary
Severe Infection Rate Excluding the First Three Months After Treatment
The infections of interest in this study were severe infections or opportunistic infectious episodes, defined as infections requiring hospitalization or prolonging hospitalization and/or documented infections by opportunistic pathogens. Infections that took place in the first 3 months of follow-up post treatment were excluded from calculations to avoid possible bias introduced in the data by the effects of conditioning.
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTL-101 Gene Therapy | Severe Infection Rate Excluding the First Three Months After Treatment | 0.20 Infection rate per person per year |
| HSCT Controls Without MRD | Severe Infection Rate Excluding the First Three Months After Treatment | 0.56 Infection rate per person per year |
| HSCT Controls With MRD | Severe Infection Rate Excluding the First Three Months After Treatment | 0.15 Infection rate per person per year |
| All HSCT Control Group | Severe Infection Rate Excluding the First Three Months After Treatment | 0.36 Infection rate per person per year |
Secondary
VCN in Peripheral Blood Mononuclear Cells (PBMCs)
PBMC VCN is a measure of the accumulation of peripheral blood leukocytes arising from engrafted, genetically modified HSC. VCN analysis was performed by ddPCR on DNA extracted from PBMC.
Time frame: 24 months
Population: Historical control groups/arms are not included in the analysis population for this outcome measure as these subjects did not receive gene therapy, and so measurement of VCN levels is not relevant
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OTL-101 Gene Therapy | VCN in Peripheral Blood Mononuclear Cells (PBMCs) | 0.972 copies/cell |
Secondary
Vector Copy Number (VCN) in Peripheral Blood (PB) Granulocytes.
Vector copy number in the PB granulocyte fraction that was T cell depleted, is a surrogate for amount of engrafted genetically modified Hematopoietic stem cell (HSC) that are producing granulocytes every 3-5 days. VCN analysis was performed by Droplet Digital PCR (ddPCR) on DNA extracted from peripheral blood granulocytes.
Time frame: 24 months
Population: Historical control groups/arms are not included in the analysis population for this outcome measure as these subjects did not receive gene therapy, and so measurement of VCN levels is not relevant
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OTL-101 Gene Therapy | Vector Copy Number (VCN) in Peripheral Blood (PB) Granulocytes. | 0.093 copies/cell |