A Study of the Efficacy and Safety of Hematopoietic Stem Cells Transduced With Lenti-D Lentiviral Vector for the Treatment of Cerebral Adrenoleukodystrophy (CALD)
Study Details
Study Description
Brief Summary
This trial assessed the efficacy and safety of autologous cluster of differentiation 34 (CD34+) hematopoietic stem cells, transduced ex-vivo with Lenti-D lentiviral vector (also called elivaldogene autotemcel or eli-cel), for the treatment of cerebral adrenoleukodystrophy (CALD). A participant's blood stem cells were collected and modified (transduced) using the Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein. After modification (transduction) with the Lenti-D lentiviral vector, the cells were transplanted back into the participant following myeloablative conditioning. Participants in this study will be continuously followed in study LTF-304.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
For study ALD-102 the Transplant Population (TP), Neutrophil Engraftment Population (NEP), and Intent-to-Treat Population (ITT) were identical.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Lenti-D Drug Product Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
Genetic: Lenti-D Drug Product (eli-cel)
Participants received a single IV infusion of Lenti-D Drug Product.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Who Were Alive and Have None of the 6 Major Functional Disabilities (MFDs) at Month 24 and Without Allo-HSCT or Rescue Cell Administration [At Month 24]
The 6 MFDs consisted of loss of communication, cortical blindness, tube feeding, total incontinence, wheelchair dependence, complete loss of voluntary movement. Month 24 MFD-Free survival criteria was defined as: alive at 24 months post-infusion; had not developed any of the MFDs by 24 months post-infusion; had not received rescue cell administration or allo-HSCT by 24 months post-infusion; and had not withdrawn from the study or had not been lost to follow-up by 24 months post-infusion. Percentage of participants who were alive and have none of the 6 major functional disabilities (MFDs) at Month 24 were reported.
- Proportion of Participants Who Had Experienced Either Acute ([>or=] Grade II) or Chronic Graft Versus Host Disease (GVHD) by Month 24 [By Month 24]
Acute GVHD graded on the Acute GVHD Grading Scale (I-IV): Grade I is characterized as mild disease, Grade II as moderate, Grade III as severe (involvement of any organ system), and Grade IV as life-threatening; chronic GVHD was determined by the Investigator. Percentage of participants who experienced with either acute (>= Grade II) or chronic GVHD at Month 24 were reported.
Secondary Outcome Measures
- Percentage of Participants Who Demonstrated Resolution of Gadolinium Positivity on Magnetic Resonance Imaging (MRI) at Month 24 [At Month 24]
Percentage of participants who demonstrated resolution of gadolinium positivity (i.e., GdE-) on MRI at Month 24 were reported.
- Time to Sustained Resolution of Gadolinium Positivity on MRI [Up to Month 24]
Sustained resolution of gadolinium positivity was defined as having at least two consecutive GdE- results by MRI without a subsequent evaluation indicating GdE+.
- Number of Participants With Change in Total Neurologic Function Score (NFS) From Baseline up to Month 24 [Baseline up to Month 24]
NFS was a 25-point score used to evaluate the severity of gross neurologic dysfunction in CALD by scoring 15 symptoms (functional domains) across 6 categories. Listed here are the 15 symptoms followed by their maximal score out of 25 points: a) Hearing / auditory processing problems-1, b) Aphasia/apraxia-1, c) Loss of communication-3, d) Vision impairment/field cut-1, e) Cortical blindness-2, f) Swallowing/other CNS dysfunctions-2, g) Tube feeding-2, h) Running difficulties/hyperreflexia-1, i) Walking difficulties/spasticity/spastic gait (no assistance)-1, j) Spastic gait (needs assistance)-2, k) Wheelchair dependence-2, l) Complete loss of voluntary movement-3, m) Episodes of incontinence -1, n) Total incontinence-2, o) Nonfebrile seizures-1. A score of "0" denoted absence of clinical signs of cerebral disease. Maximal signs within a domain score the total of all grades within that domain. Number of participants with change in total NFS from baseline up to Month 24 were reported.
- Major Functional Disability (MFD)-Free Survival Rate [At 24 months after Lenti-D drug infusion]
MFD-free survival rate was defined as percentage of participants from drug product infusion to either second transplant, MFD, or death due to any cause, whichever occurs first. MFD-free survival rate was analyzed using Kaplan-Meier Analysis. Kaplan-Meier estimated MFD-free survival rate at 24 months after Lenti-D drug infusion was reported.
- Overall Survival Rate [At 24 months after Lenti-D drug infusion]
Overall survival rate was defined as percentage of participants alive from date of Lenti-D drug product infusion (Day 0) to date of death of all causes. Overall survival rate was censored at the date of last visit if the participant were alive. Participants who are alive were censored at the date of last contact. Overall survival rate was analyzed using Kaplan-Meier Analysis. Kaplan-Meier estimated overall survival rate at 24 months after Lenti-D drug infusion was reported.
- Proportion of Participants With Neutrophil Engraftment by 42 Days Post-drug Product Infusion [By 42 days post-drug infusion]
Neutrophil engraftment (NE) was defined as achieving 3 consecutive absolute neutrophil count (ANC) laboratory values of >= 0.5×10^9 cells/Liter (L) (after initial post-infusion nadir) obtained on different days by 42 days post-infusion of Lenti-D Drug Product (Relative Day 43). Percentage of participants with neutrophil engraftment by 42 Days post-drug product infusion were reported.
- Time to Neutrophil Engraftment Post-drug Product Infusion [By 42 days post-drug infusion]
Neutrophil Engraftment was defined as achieving 3 consecutive ANC laboratory values of >= 0.5×10^9 cells/L (after initial post-infusion nadir) obtained on different days by 42 days post-infusion of Lenti-D Drug Product (Relative Day 43). Time to neutrophil engraftment post-drug product infusion was reported.
- Proportion of Participants With Platelet Engraftment by Month 24 [By Month 24]
Platelet Engraftment was defined as achieving 3 consecutive unsupported platelet counts of >=20 × 10^9 cells/L (after initial post-infusion nadir) obtained on different days while no platelet transfusions were administered for 7 days immediately preceding and during the evaluation period. The first day of 3 consecutive platelet counts >=20 × 10^9 cells/L was the day of PE. Percentage of participants with Platelet Engraftment by Month 24 (Rel Day 730) were reported.
- Time to Platelet Engraftment Post-drug Product Infusion [By Month 24]
Platelet Engraftment was defined as achieving 3 consecutive unsupported platelet counts of > or =20 × 10^9 cells/L (after initial post-infusion nadir) obtained on different days while no platelet transfusions were administered for 7 days immediately preceding and during the evaluation period. The first day of 3 consecutive platelet counts >=20 × 10^9 cells/L was the day of PE. Time to Platelet Engraftment post-drug product infusion up to Month 24 was reported.
- Proportion of Participants With Engraftment Failure By Month 24 [By Month 24]
Participants were considered to have primary engraftment failure if they did not achieve NE by Relative Day 43. A participant was considered to have secondary engraftment failure if they achieved and then subsequently lost NE by the Month 24, i.e., if they met both the conditions; Achieved NE by Relative Day 43 as defined above and had sustained decline in ANC to < 0.5×10^9 cells/L for 3 consecutive measurements on different days after Relative Day 43, without alternate etiology. First day of the 3 consecutive ANC decline to < 0.5×10^9 cells/L was considered the day of secondary engraftment failure. Percentage of participants with both primary and secondary engraftment failure at Month 24 were reported.
- Proportion of Participants Who Underwent a Subsequent Allo-Hematopoietic Stem Cell (HSC) Infusion by Month 24 [By Month 24]
Percentage of Participants who have undergone a subsequent allo-HSC infusion at Month 24 were reported.
- Percentage of Participants With Transplant-related Mortality Through 100 and 365 Days Post-drug Product Infusion [From time of drug product infusion through 100 and 365 days post-drug product infusion]
Transplant-related mortality was determined by the Investigator in participants who had died from transplant-related causes by 100 days post-drug product infusion (Rel Day 101) or 365 days post-drug product infusion (Rel Day 366) respectively or had been followed to at least Rel Day 101 or 366 respectively if no events yet. Percentage of participants with transplant-related mortality through 100 and 365 days post-drug product infusion were reported.
- Percentage of Participants With Adverse Events (AEs), Serious AEs, Grade >=3 AE, Related AEs, Related SAEs and Related Grade >=3 AEs [From date of informed consent up to Month 24]
Adverse event was defined as any untoward medical occurrence associated with the use of a drug product in participants, whether or not considered drug related. SAE was any AE, occurring at any dose and regardless of causality, that resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or was considered an important medical event that may jeopardize the participant and may require medical or surgical intervention to prevent an outcome listed previously. Percentage of participants with all AEs, all SAEs, all drug-product related AEs and SAEs Grade >=3 (severe or medically significant but not immediately life threatening AE) and related Grade >=3 AEs were reported.
- Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 [From time of drug product infusion up to Month 24]
Laboratory parameters included hematology (Leukocytes [with a threshold (TS) range <4.0 x 10^9/L, >=18 x 10^9/L], Neutrophils [<1.0 x 10^9/L], Erythrocytes [<=3.0 x 10^12/L], Platelets [<=75 x 10^9/L]); clinical chemistry (Sodium [<=126 millimoles per liter (mmol/L), >=156 mmol/L], Potassium [<=3 mmol/L, >=6 mmol/L], Glucose [<=3.0 mmol/L], Urea Nitrogen [>=10.7 mmol/L], Creatinine [>=150 umol/L]) and liver function tests (LFT) (Alanine Aminotransferase [ALA]. Aspartate Aminotransferase [ASA], Alkaline Phosphatase [AP] with TS range of >=3 x upper limit of normal (ULN), Bilirubin [>=34.2 micromoles per liter (umol/L)]). Clinical significance was decided by investigator.
- Number of Emergency Room Visits (Post-Neutrophil Engraftment) By Month 24 [From Post-Neutrophil Engraftment up to Month 24]
Number of emergency room visits (post-neutrophil engraftment) up to Month 24 were reported.
- Number of In-patient Hospitalizations (Post-Neutrophil Engraftment) By Month 24 [From post-neutrophil engraftment up to Month 24]
Number of In-patient hospitalizations (post-neutrophil engraftment) by Month 24 were reported.
- Duration of In-patient Hospitalizations (Post-Neutrophil Engraftment) up to Month 24 [From post-neutrophil engraftment up to Month 24]
Duration of in-patient hospitalizations was calculated as: Duration = (Date of hospital discharge) - (Date of hospital admission before NE) + 1. Duration of In-patient hospitalizations (post-neutrophil engraftment) up to Month 24 was reported.
- Number of Intensive Care Units (ICU) Stays (Post-neutrophil Engraftment) By Month 24 [From post-neutrophil engraftment up to Month 24]
Number of ICU Stays (Post-neutrophil Engraftment) By Month 24 were reported.
- Duration of ICU Stays (Post-neutrophil Engraftment) By Month 24 [From post-neutrophil engraftment up to Month 24]
Duration of ICU Stays was calculated as: Duration = (Date of hospital discharge) - (Date of hospital admission before NE) + 1. Duration of ICU Stays (Post-neutrophil Engraftment) by Month 24 was reported.
- Number of Participants With Vector-Derived Replication Competent Lentivirus (RCL) Detected by Month 24 [By Month 24]
Number of Participants with Vector-derived RCL detected at Month 24 were reported. Screening participants blood samples for RCL at month 24 following Lenti-D Drug infusion was performed, with the more rigorous co-culture assays used to distinguish any false positives as applicable.
- Number of Participants With Insertional Oncogenesis By Month 24 [By Month 24]
Insertional oncogenesis including myelodysplasia, leukemia, lymphoma. Number of participants with insertional oncogenesis at Month 24 were reported.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Informed consent was obtained from a competent custodial parent or guardian with legal capacity to execute a local institutional review board (IRB)/Independent Ethics Committee (IEC) approved consent (informed assent will be sought from capable participants, in accordance with the directive of the IRB/IEC and with local requirements).
-
Males aged 17 years and younger, at the time of parental/guardian consent and, where appropriate, participant assent.
-
Active cerebral adrenoleukodystrophy (ALD) as defined by:
-
Elevated very long chain fatty acids (VLCFA) values, and
-
Active CNS disease established by central radiographic review of brain magnetic resonance imaging (MRI) demonstrating:
-
Loes score between 0.5 and 9 (inclusive) on the 34-point scale, and
-
Gadolinium enhancement on MRI of demyelinating lesions.
-
NFS less than or equal to (<or=) 1.
Exclusion Criteria:
-
Receipt of an allogeneic transplant or gene therapy.
-
Availability of a willing 10/10 HLA-matched sibling donor (excluding female heterozygotes).
-
Use of statins, Lorenzo's Oil, or dietary regimens used to lower very long chain fatty acids (VLCFA) levels. Note: participants must discontinue use of these medications at time of consent.
-
Receipt of an investigational study drug or procedure within 3 months before Screening that might confound study outcomes. Use of investigational study drugs is prohibited throughout the course of the study.
-
Any conditions that make it impossible to perform MRI studies (including allergies to anesthetics or contrast agents).
-
Hematological compromise as evidenced by:
-
Peripheral blood absolute neutrophil count (ANC) count < 1500 cells/ cubic milli meter (mm3),
-
Platelet count < 100,000 cells/mm3, or
-
Hemoglobin < 10 gram per deciliter (g/dL).
-
Uncorrected bleeding disorder.
- Hepatic compromise as evidenced by:
-
Aspartate transaminase (AST) value > 2.5×upper limit of normal (ULN)
-
Alanine transaminase (ALT) value > 2.5×ULN
-
Total bilirubin value > 3.0 milligram per deciliter (mg/dL), except if there is a diagnosis of Gilbert's Syndrome and the participant is otherwise stable
-
Renal compromise as evidenced by abnormal renal function (actual or calculated creatinine clearance < 50 milliliter per minute [mL/min])
-
Cardiac compromise as evidenced by left ventricular ejection fraction <40 percent (%)
-
Immediate family member with a known or suspected Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome, and familial adenomatous polyposis).
-
Clinically significant active bacterial, viral, fungal, parasitic, or prion-associated infection
-
Positive for human immunodeficiency virus type 1 or 2 (HIV-1, HIV-2); hepatitis B; hepatitis C; human T lymphotrophic virus 1 (HTLV-1). (Note that participants who have been vaccinated against hepatitis B [hepatitis B surface antibody-positive] who are negative for other markers of prior hepatitis B infection [eg, negative for hepatitis B core antibody (Ab)] are eligible. Participants with past exposure to hepatitis B virus (HBV [HBcAb positive and/or HBeAb positive]) are also eligible for the study provided they have a negative test for HBV DNA. Also note that participants who are positive for anti-hepatitis C antibody are eligible as long as they have a negative hepatitis C viral load.
-
Any clinically significant cardiovascular or pulmonary disease, or other disease or condition that would be contraindicated for any of the other study procedures.
-
Absence of adequate contraception for fertile participants. Male participants and their female partners are required to use two different effective methods of contraception from Screening through at least 6 months after drug product infusion. If subjects are truly sexually abstinent (where true sexual abstinence is defined as being in line with the preferred and usual lifestyle of the subject), no second method is required.
-
Any contraindications to the use of granulocyte colony stimulating (G-CSF) during the mobilization of HSCs, and any contraindications to the use of busulfan or cyclophosphamide, including known hypersensitivity to the active substances or to any of the excipients in their formulations.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mattel Children's Hospital UCLA/Ronald Reagan UCLA Medical Center | Los Angeles | California | United States | 90095 |
| 2 | Boston Children's Hospital/Massachusetts General Hospital | Boston | Massachusetts | United States | 02115 |
| 3 | University of Minnesota | Minneapolis | Minnesota | United States | 55455 |
| 4 | Medeos SRL | Buenos Aires | Argentina | C1022 | |
| 5 | Women and Children's Hospital | North Adelaide | South Australia | Australia | 5006 |
| 6 | Hôpital Bicêtre | Le Kremlin-Bicêtre Cedex | France | 94275 | |
| 7 | University of Leipzig | Leipzig | Germany | 04103 | |
| 8 | Great Ormond Street Hospital for Children NHS Foundation Trust | London | United Kingdom | WC1N3JH |
Sponsors and Collaborators
- bluebird bio
Investigators
- Study Director: Jakob Sieker, MD., bluebird bio, Inc.
- Principal Investigator: David Williams, MD, Boston Children's Hospital
- Principal Investigator: Christine Duncan, MD, Boston Children's Hospital
- Principal Investigator: Florian Eichler, MD, Massachusetts General Hospital
- Principal Investigator: Satiro de Oliveira, MD, University of California, Los Angeles
- Principal Investigator: Paul Orchard, MD, University of Minnesota
- Principal Investigator: Adrian Thrasher, MD, PhD, Great Ormond Street Hospital for Chidren NHS Foundation Trust
- Principal Investigator: Patrick Aubourg, MD, PhD, Hôpital Bicêtre
- Principal Investigator: Jorn-Sven Kuhl, MD, University of Leipzig
- Principal Investigator: Nicholas Smith, MD, Women and Children's Hospital
- Principal Investigator: Hernan Amartino, MD, Medeos SRL
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- ALD-102
- 2011-001953-10
Study Results
Participant Flow
| Recruitment Details | This study was conducted at 8 centers from 21 August 2013 (first participants first visit) to 26 March 2021 (last participants last visit). |
|---|---|
| Pre-assignment Detail | A total of 32 Participants were enrolled and treated in this study. All male participants with Cerebral Adrenoleukodystrophy (CALD) were treated with Lenti-D Drug Product also referred to as eli-cel (elivaldogene autotemcel) in this study. For study ALD-102 the Transplant Population (TP), Neutrophil Engraftment Population (NEP), and Intent-to-Treat Population (ITT) are identical. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contains cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. Neutrophil Engraftment Population (NEP) is identical to the Transplant Population (TP). |
| Period Title: Overall Study | |
| STARTED | 32 |
| COMPLETED | 29 |
| NOT COMPLETED | 3 |
Baseline Characteristics
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contains cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Overall Participants | 32 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
6
(2.4)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
0
0%
|
| Male |
32
100%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
12
37.5%
|
| Not Hispanic or Latino |
17
53.1%
|
| Unknown or Not Reported |
3
9.4%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
1
3.1%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
1
3.1%
|
| White |
15
46.9%
|
| More than one race |
5
15.6%
|
| Unknown or Not Reported |
10
31.3%
|
Outcome Measures
| Title | Percentage of Participants Who Were Alive and Have None of the 6 Major Functional Disabilities (MFDs) at Month 24 and Without Allo-HSCT or Rescue Cell Administration |
|---|---|
| Description | The 6 MFDs consisted of loss of communication, cortical blindness, tube feeding, total incontinence, wheelchair dependence, complete loss of voluntary movement. Month 24 MFD-Free survival criteria was defined as: alive at 24 months post-infusion; had not developed any of the MFDs by 24 months post-infusion; had not received rescue cell administration or allo-HSCT by 24 months post-infusion; and had not withdrawn from the study or had not been lost to follow-up by 24 months post-infusion. Percentage of participants who were alive and have none of the 6 major functional disabilities (MFDs) at Month 24 were reported. |
| Time Frame | At Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Transplant Population (TP) consisted of participants who received Lenti-D Drug Product infusion. Evaluable participants were defined as those who had been followed for 24 months (i.e. Rel DLC >= 730) or have had completed Month 24, or discontinued from the study but would have been followed for 24 months if still on the study (i.e. Rel Day of data cut >= 730). |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contains cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 32 |
| Number (95% Confidence Interval) [Percentage of participants] |
90.6
283.1%
|
| Title | Proportion of Participants Who Had Experienced Either Acute ([>or=] Grade II) or Chronic Graft Versus Host Disease (GVHD) by Month 24 |
|---|---|
| Description | Acute GVHD graded on the Acute GVHD Grading Scale (I-IV): Grade I is characterized as mild disease, Grade II as moderate, Grade III as severe (involvement of any organ system), and Grade IV as life-threatening; chronic GVHD was determined by the Investigator. Percentage of participants who experienced with either acute (>= Grade II) or chronic GVHD at Month 24 were reported. |
| Time Frame | By Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP consisted of participants who received Lenti-D Drug Product infusion. To be evaluable participants must have either experienced the event by Month 24 (Rel Day 730) or have been followed for at least 12 months (Rel Day of DLC >= 365) without GVHD. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 32 |
| Number (95% Confidence Interval) [Percentage of participants] |
0.0
0%
|
| Title | Percentage of Participants Who Demonstrated Resolution of Gadolinium Positivity on Magnetic Resonance Imaging (MRI) at Month 24 |
|---|---|
| Description | Percentage of participants who demonstrated resolution of gadolinium positivity (i.e., GdE-) on MRI at Month 24 were reported. |
| Time Frame | At Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP consisted of participants who received Lenti-D Drug Product infusion. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure. Evaluable participants are defined as participants who completed the Month 24 assessment. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 30 |
| Number (95% Confidence Interval) [Percentage of participants] |
86.7
270.9%
|
| Title | Time to Sustained Resolution of Gadolinium Positivity on MRI |
|---|---|
| Description | Sustained resolution of gadolinium positivity was defined as having at least two consecutive GdE- results by MRI without a subsequent evaluation indicating GdE+. |
| Time Frame | Up to Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP consisted of participants who received Lenti-D Drug Product infusion. Here, "Overall Number of participants Analyzed" signifies those participants who were evaluable for this outcome measure. Evaluable participants are defined as participants who have completed the Month 24 assessment of GdE status. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 24 |
| Median (Full Range) [Days] |
77
|
| Title | Number of Participants With Change in Total Neurologic Function Score (NFS) From Baseline up to Month 24 |
|---|---|
| Description | NFS was a 25-point score used to evaluate the severity of gross neurologic dysfunction in CALD by scoring 15 symptoms (functional domains) across 6 categories. Listed here are the 15 symptoms followed by their maximal score out of 25 points: a) Hearing / auditory processing problems-1, b) Aphasia/apraxia-1, c) Loss of communication-3, d) Vision impairment/field cut-1, e) Cortical blindness-2, f) Swallowing/other CNS dysfunctions-2, g) Tube feeding-2, h) Running difficulties/hyperreflexia-1, i) Walking difficulties/spasticity/spastic gait (no assistance)-1, j) Spastic gait (needs assistance)-2, k) Wheelchair dependence-2, l) Complete loss of voluntary movement-3, m) Episodes of incontinence -1, n) Total incontinence-2, o) Nonfebrile seizures-1. A score of "0" denoted absence of clinical signs of cerebral disease. Maximal signs within a domain score the total of all grades within that domain. Number of participants with change in total NFS from baseline up to Month 24 were reported. |
| Time Frame | Baseline up to Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP consisted of participants who received Lenti-D Drug Product infusion. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure. Evaluable participants are defined as participants who have non-missing Baseline and have completed the Month 24 NFS assessment. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 30 |
| Count of Participants [Participants] |
4
12.5%
|
| Title | Major Functional Disability (MFD)-Free Survival Rate |
|---|---|
| Description | MFD-free survival rate was defined as percentage of participants from drug product infusion to either second transplant, MFD, or death due to any cause, whichever occurs first. MFD-free survival rate was analyzed using Kaplan-Meier Analysis. Kaplan-Meier estimated MFD-free survival rate at 24 months after Lenti-D drug infusion was reported. |
| Time Frame | At 24 months after Lenti-D drug infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP consisted of participants who received Lenti-D Drug Product infusion. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 32 |
| Number (95% Confidence Interval) [Percentage of participants] |
90.6
283.1%
|
| Title | Overall Survival Rate |
|---|---|
| Description | Overall survival rate was defined as percentage of participants alive from date of Lenti-D drug product infusion (Day 0) to date of death of all causes. Overall survival rate was censored at the date of last visit if the participant were alive. Participants who are alive were censored at the date of last contact. Overall survival rate was analyzed using Kaplan-Meier Analysis. Kaplan-Meier estimated overall survival rate at 24 months after Lenti-D drug infusion was reported. |
| Time Frame | At 24 months after Lenti-D drug infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP consisted of participants who received Lenti-D Drug Product infusion. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 32 |
| Number (95% Confidence Interval) [Percentage of participants] |
96.7
302.2%
|
| Title | Proportion of Participants With Neutrophil Engraftment by 42 Days Post-drug Product Infusion |
|---|---|
| Description | Neutrophil engraftment (NE) was defined as achieving 3 consecutive absolute neutrophil count (ANC) laboratory values of >= 0.5×10^9 cells/Liter (L) (after initial post-infusion nadir) obtained on different days by 42 days post-infusion of Lenti-D Drug Product (Relative Day 43). Percentage of participants with neutrophil engraftment by 42 Days post-drug product infusion were reported. |
| Time Frame | By 42 days post-drug infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP consisted of participants who received Lenti-D Drug Product infusion. Evaluable participants for NE if they achieved neutrophil engraftment by Rel Day 43, or had discontinued or were lost to follow-up before Rel Day 43 without achieving NE, or had been followed to at least Rel Day 43 but had not achieved NE. Participants who discontinued or were lost to follow-up before Rel Day 43 without achieving NE were considered failures for NE. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 32 |
| Number (95% Confidence Interval) [Percentage of participants] |
100.0
312.5%
|
| Title | Time to Neutrophil Engraftment Post-drug Product Infusion |
|---|---|
| Description | Neutrophil Engraftment was defined as achieving 3 consecutive ANC laboratory values of >= 0.5×10^9 cells/L (after initial post-infusion nadir) obtained on different days by 42 days post-infusion of Lenti-D Drug Product (Relative Day 43). Time to neutrophil engraftment post-drug product infusion was reported. |
| Time Frame | By 42 days post-drug infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP consisted of Participants who received Lenti-D Drug Product infusion. Participants were evaluable for NE if: 1) They achieved Neutrophil Engraftment by Rel Day 43 2)Had discontinued or were lost to follow-up before Rel Day 43 without achieving NE 3) Had been followed to at least Rel Day 43 but had not achieved NE. Participants who discontinued or were lost to follow-up before Rel Day 43 without achieving NE were considered failures for NE. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 32 |
| Median (Full Range) [Days] |
13.0
|
| Title | Proportion of Participants With Platelet Engraftment by Month 24 |
|---|---|
| Description | Platelet Engraftment was defined as achieving 3 consecutive unsupported platelet counts of >=20 × 10^9 cells/L (after initial post-infusion nadir) obtained on different days while no platelet transfusions were administered for 7 days immediately preceding and during the evaluation period. The first day of 3 consecutive platelet counts >=20 × 10^9 cells/L was the day of PE. Percentage of participants with Platelet Engraftment by Month 24 (Rel Day 730) were reported. |
| Time Frame | By Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP consisted of participants who received Lenti-D Drug Product infusion. Participants were evaluable for platelet engraftment if they achieved Platelet Engraftment by 24 months (Rel Day 730), or had been followed for at least 24 months without any events. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 32 |
| Number (95% Confidence Interval) [Percentage of participants] |
100
312.5%
|
| Title | Time to Platelet Engraftment Post-drug Product Infusion |
|---|---|
| Description | Platelet Engraftment was defined as achieving 3 consecutive unsupported platelet counts of > or =20 × 10^9 cells/L (after initial post-infusion nadir) obtained on different days while no platelet transfusions were administered for 7 days immediately preceding and during the evaluation period. The first day of 3 consecutive platelet counts >=20 × 10^9 cells/L was the day of PE. Time to Platelet Engraftment post-drug product infusion up to Month 24 was reported. |
| Time Frame | By Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP consisted of participants who received Lenti-D Drug Product infusion. Participants were evaluable for Platelet Engraftment if they had achieved platelet engraftment by 24 months (Rel Day 730), or had been followed for at least 24 months without any events. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 32 |
| Median (Full Range) [Days] |
32
|
| Title | Proportion of Participants With Engraftment Failure By Month 24 |
|---|---|
| Description | Participants were considered to have primary engraftment failure if they did not achieve NE by Relative Day 43. A participant was considered to have secondary engraftment failure if they achieved and then subsequently lost NE by the Month 24, i.e., if they met both the conditions; Achieved NE by Relative Day 43 as defined above and had sustained decline in ANC to < 0.5×10^9 cells/L for 3 consecutive measurements on different days after Relative Day 43, without alternate etiology. First day of the 3 consecutive ANC decline to < 0.5×10^9 cells/L was considered the day of secondary engraftment failure. Percentage of participants with both primary and secondary engraftment failure at Month 24 were reported. |
| Time Frame | By Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP consisted of participants who received Lenti-D Drug Product infusion. Here, "Overall number of participants analyzed" signified those participants who were evaluable for this outcome measure. Evaluable participants for secondary Neutrophil Engraftment failure included participants who had achieved neutrophil engraftment, and 1) have secondary engraftment failure by Rel Day 730, or 2) had been followed for at least 24 months without any events. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 29 |
| Number (95% Confidence Interval) [Percentage of participants] |
0.0
0%
|
| Title | Proportion of Participants Who Underwent a Subsequent Allo-Hematopoietic Stem Cell (HSC) Infusion by Month 24 |
|---|---|
| Description | Percentage of Participants who have undergone a subsequent allo-HSC infusion at Month 24 were reported. |
| Time Frame | By Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP consisted of participants who received Lenti-D Drug Product infusion. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure. Evaluable participants were defined as those who decided to receive subsequent allo-HSCT thus discontinued from the study, or participants who have been followed for at least 24 months (Rel Day of last contact >= 730 or completed Month 24 visit) if no events. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 31 |
| Number (95% Confidence Interval) [Percentage of participants] |
6.5
20.3%
|
| Title | Percentage of Participants With Transplant-related Mortality Through 100 and 365 Days Post-drug Product Infusion |
|---|---|
| Description | Transplant-related mortality was determined by the Investigator in participants who had died from transplant-related causes by 100 days post-drug product infusion (Rel Day 101) or 365 days post-drug product infusion (Rel Day 366) respectively or had been followed to at least Rel Day 101 or 366 respectively if no events yet. Percentage of participants with transplant-related mortality through 100 and 365 days post-drug product infusion were reported. |
| Time Frame | From time of drug product infusion through 100 and 365 days post-drug product infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP consisted of participants who received Lenti-D Drug Product infusion. Evaluable participants included participants who had died from transplant-related causes by Rel Day 101 or 366 respectively or have been followed to at least Rel Day 101 or 366 respectively if no events yet. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 32 |
| Transplant-related mortality within 100 days |
0.0
0%
|
| Transplant-related mortality within 365 days |
0.0
0%
|
| Title | Percentage of Participants With Adverse Events (AEs), Serious AEs, Grade >=3 AE, Related AEs, Related SAEs and Related Grade >=3 AEs |
|---|---|
| Description | Adverse event was defined as any untoward medical occurrence associated with the use of a drug product in participants, whether or not considered drug related. SAE was any AE, occurring at any dose and regardless of causality, that resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or was considered an important medical event that may jeopardize the participant and may require medical or surgical intervention to prevent an outcome listed previously. Percentage of participants with all AEs, all SAEs, all drug-product related AEs and SAEs Grade >=3 (severe or medically significant but not immediately life threatening AE) and related Grade >=3 AEs were reported. |
| Time Frame | From date of informed consent up to Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population consisted of participants who initiated any study procedures, beginning with mobilization by G-CSF |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 32 |
| Percentage of participants with at least 1 AE |
100.0
312.5%
|
| Percentage of participants with at least 1 SAE |
65.6
205%
|
| Percentage of participants with at least 1 AE related to Lenti-D Drug |
9.4
29.4%
|
| Percentage of participants with at least 1 SAE related to Lenti-D Drug |
3.1
9.7%
|
| Percentage of participants with at least 1 Grade >=3 AE |
93.8
293.1%
|
| Percentage of participants with at least 1 Grade>=3 AE related to Lenti-D Drug |
3.1
9.7%
|
| Title | Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 |
|---|---|
| Description | Laboratory parameters included hematology (Leukocytes [with a threshold (TS) range <4.0 x 10^9/L, >=18 x 10^9/L], Neutrophils [<1.0 x 10^9/L], Erythrocytes [<=3.0 x 10^12/L], Platelets [<=75 x 10^9/L]); clinical chemistry (Sodium [<=126 millimoles per liter (mmol/L), >=156 mmol/L], Potassium [<=3 mmol/L, >=6 mmol/L], Glucose [<=3.0 mmol/L], Urea Nitrogen [>=10.7 mmol/L], Creatinine [>=150 umol/L]) and liver function tests (LFT) (Alanine Aminotransferase [ALA]. Aspartate Aminotransferase [ASA], Alkaline Phosphatase [AP] with TS range of >=3 x upper limit of normal (ULN), Bilirubin [>=34.2 micromoles per liter (umol/L)]). Clinical significance was decided by investigator. |
| Time Frame | From time of drug product infusion up to Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population consisted of participants who initiated any study procedures, beginning with mobilization by G-CSF. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 32 |
| Hematology: Leukocytes (<4.0 x 10^9/L) |
100.0
312.5%
|
| Hematology: Leukocytes (>=18 x 10^9/L) |
0.0
0%
|
| Hematology: Neutrophils (<1.0 x 10^9/L) |
78.1
244.1%
|
| Hematology: Erythrocytes (<=3.0 x 10^12/L) |
43.8
136.9%
|
| Hematology: Platelets (<=75 x 10^9/L) |
96.9
302.8%
|
| Chemistry: Sodium (<=126 mmol/L) |
0.0
0%
|
| Chemistry: Sodium (>=156 mmol/L) |
0.0
0%
|
| Chemistry: Potassium (<=3 mmol/L) |
21.9
68.4%
|
| Chemistry: Potassium (>=6 mmol/L) |
0.0
0%
|
| Chemistry: Glucose (<=3.0 mmol/L) |
0.0
0%
|
| Chemistry: Urea Nitrogen (>=10.7 mmol/L) |
0.0
0%
|
| Chemistry: Creatinine (>=150 umol/L) |
0.0
0%
|
| LFT: ALA (>=3 x ULN) |
3.1
9.7%
|
| LFT: ASA (>=3 x ULN) |
3.1
9.7%
|
| LFT: AP (>=3 x ULN) |
0.0
0%
|
| LFT: Bilirubin (>=34.2 umol/L) |
0.0
0%
|
| Title | Number of Emergency Room Visits (Post-Neutrophil Engraftment) By Month 24 |
|---|---|
| Description | Number of emergency room visits (post-neutrophil engraftment) up to Month 24 were reported. |
| Time Frame | From Post-Neutrophil Engraftment up to Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The successful Neutrophil Engraftment Population (NEP) consisted of participants who achieved NE defined as having 3 consecutive ANC laboratory values of >= 0.5×10^9 cells/L (after initial post-infusion) obtained on different days of post-infusion of Lenti-D Drug Product. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 32 |
| Number [Emergency room visits] |
13
|
| Title | Number of In-patient Hospitalizations (Post-Neutrophil Engraftment) By Month 24 |
|---|---|
| Description | Number of In-patient hospitalizations (post-neutrophil engraftment) by Month 24 were reported. |
| Time Frame | From post-neutrophil engraftment up to Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The successful NEP consisted of participants who achieved NE defined as having 3 consecutive ANC laboratory values of >= 0.5×10^9 cells/L (after initial post-infusion) obtained on different days of post-infusion of Lenti-D Drug Product. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 32 |
| Number [Hospitalizations] |
14
|
| Title | Duration of In-patient Hospitalizations (Post-Neutrophil Engraftment) up to Month 24 |
|---|---|
| Description | Duration of in-patient hospitalizations was calculated as: Duration = (Date of hospital discharge) - (Date of hospital admission before NE) + 1. Duration of In-patient hospitalizations (post-neutrophil engraftment) up to Month 24 was reported. |
| Time Frame | From post-neutrophil engraftment up to Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The successful NEP consisted of participants who achieved NE defined as having 3 consecutive ANC laboratory values of >= 0.5×10^9 cells/L (after initial post-infusion) obtained on different days of post-infusion of Lenti-D Drug Product. Here, "overall number of participants analyzed" signified those participants who were evaluable for this outcome measure. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 14 |
| Median (Full Range) [Days] |
3.0
|
| Title | Number of Intensive Care Units (ICU) Stays (Post-neutrophil Engraftment) By Month 24 |
|---|---|
| Description | Number of ICU Stays (Post-neutrophil Engraftment) By Month 24 were reported. |
| Time Frame | From post-neutrophil engraftment up to Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The successful NEP consisted of participants who achieved NE defined as having 3 consecutive ANC laboratory values of >= 0.5×10^9 cells/L (after initial post-infusion) obtained on different days by of post-infusion of Lenti-D Drug Product. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 32 |
| Number [ICU Stays] |
1
|
| Title | Duration of ICU Stays (Post-neutrophil Engraftment) By Month 24 |
|---|---|
| Description | Duration of ICU Stays was calculated as: Duration = (Date of hospital discharge) - (Date of hospital admission before NE) + 1. Duration of ICU Stays (Post-neutrophil Engraftment) by Month 24 was reported. |
| Time Frame | From post-neutrophil engraftment up to Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The successful NEP consisted of participants who achieved NE defined as having 3 consecutive ANC laboratory values of >= 0.5×10^9 cells/L (after initial post-infusion) obtained on different days of post-infusion of Lenti-D Drug Product. Here, "overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 1 |
| Median (Full Range) [Days] |
12.0
|
| Title | Number of Participants With Vector-Derived Replication Competent Lentivirus (RCL) Detected by Month 24 |
|---|---|
| Description | Number of Participants with Vector-derived RCL detected at Month 24 were reported. Screening participants blood samples for RCL at month 24 following Lenti-D Drug infusion was performed, with the more rigorous co-culture assays used to distinguish any false positives as applicable. |
| Time Frame | By Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP consisted of participants who received Lenti-D Drug Product infusion. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 32 |
| Count of Participants [Participants] |
0
0%
|
| Title | Number of Participants With Insertional Oncogenesis By Month 24 |
|---|---|
| Description | Insertional oncogenesis including myelodysplasia, leukemia, lymphoma. Number of participants with insertional oncogenesis at Month 24 were reported. |
| Time Frame | By Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| TP consisted of participants who received Lenti-D Drug Product infusion. |
| Arm/Group Title | Lenti-D Drug Product |
|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. |
| Measure Participants | 32 |
| Count of Participants [Participants] |
0
0%
|
Adverse Events
| Time Frame | From date of informed consent up to Month 24 | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Lenti-D Drug Product | |
| Arm/Group Description | Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (>=) 5.0 × 10^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contains cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0. | |
All Cause Mortality |
||
| Lenti-D Drug Product | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/32 (3.1%) | |
Serious Adverse Events |
||
| Lenti-D Drug Product | ||
| Affected / at Risk (%) | # Events | |
| Total | 21/32 (65.6%) | |
| Blood and lymphatic system disorders | ||
| Febrile neutropenia | 8/32 (25%) | 8 |
| Cardiac disorders | ||
| Cardio-respiratory arrest | 1/32 (3.1%) | 1 |
| Endocrine disorders | ||
| Adrenal insufficiency | 2/32 (6.3%) | 2 |
| Gastrointestinal disorders | ||
| Abdominal pain | 1/32 (3.1%) | 1 |
| Stomatitis | 1/32 (3.1%) | 1 |
| Vomiting | 1/32 (3.1%) | 1 |
| General disorders | ||
| Pyrexia | 6/32 (18.8%) | 6 |
| Hepatobiliary disorders | ||
| Acute hepatic failure | 1/32 (3.1%) | 1 |
| Infections and infestations | ||
| Vascular device infection | 3/32 (9.4%) | 3 |
| Cystitis viral | 1/32 (3.1%) | 1 |
| Gastroenteritis | 1/32 (3.1%) | 1 |
| Influenza | 1/32 (3.1%) | 1 |
| Otitis media | 1/32 (3.1%) | 1 |
| Viral infection | 1/32 (3.1%) | 1 |
| Sinusitis | 1/32 (3.1%) | 1 |
| Injury, poisoning and procedural complications | ||
| Head injury | 1/32 (3.1%) | 1 |
| Procedural Pain | 1/32 (3.1%) | 1 |
| Spinal fracture | 1/32 (3.1%) | 1 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 1/32 (3.1%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Rhabdomyolysis | 1/32 (3.1%) | 1 |
| Nervous system disorders | ||
| Dyskinesia | 1/32 (3.1%) | 1 |
| Neurological decompensation | 1/32 (3.1%) | 1 |
| Seizure | 1/32 (3.1%) | 1 |
| Renal and urinary disorders | ||
| Acute kidney injury | 1/32 (3.1%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Respiratory distress | 1/32 (3.1%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Lenti-D Drug Product | ||
| Affected / at Risk (%) | # Events | |
| Total | 32/32 (100%) | |
| Blood and lymphatic system disorders | ||
| Thrombocytopenia | 31/32 (96.9%) | 31 |
| Anaemia | 31/32 (96.9%) | 31 |
| Neutropenia | 30/32 (93.8%) | 30 |
| Febrile neutropenia | 20/32 (62.5%) | 20 |
| Leukopenia | 11/32 (34.4%) | 11 |
| Lymphopenia | 6/32 (18.8%) | 6 |
| Cardiac disorders | ||
| Bradycardia | 2/32 (6.3%) | 2 |
| Tachycardia | 2/32 (6.3%) | 2 |
| Sinus bradycardia | 2/32 (6.3%) | 2 |
| Gastrointestinal disorders | ||
| Nausea | 30/32 (93.8%) | 30 |
| Vomiting | 28/32 (87.5%) | 28 |
| Stomatitis | 27/32 (84.4%) | 27 |
| Abdominal pain | 17/32 (53.1%) | 17 |
| Diarrhoea | 14/32 (43.8%) | 14 |
| Constipation | 9/32 (28.1%) | 9 |
| Oral pain | 3/32 (9.4%) | 3 |
| Proctitis | 3/32 (9.4%) | 3 |
| Toothache | 2/32 (6.3%) | 2 |
| General disorders | ||
| Pyrexia | 11/32 (34.4%) | 11 |
| Catheter site pain | 8/32 (25%) | 8 |
| Catheter site hemorrhage | 2/32 (6.3%) | 2 |
| Fatigue | 2/32 (6.3%) | 2 |
| Infections and infestations | ||
| Vascular device infection | 3/32 (9.4%) | 3 |
| Enterobiasis | 2/32 (6.3%) | 2 |
| Oral candiasis | 2/32 (6.3%) | 2 |
| Rhinovirus infection | 2/32 (6.3%) | 2 |
| Viral infection | 2/32 (6.3%) | 2 |
| Injury, poisoning and procedural complications | ||
| Procedural Pain | 7/32 (21.9%) | 7 |
| Allergic transfusion reaction | 4/32 (12.5%) | 4 |
| Fall | 2/32 (6.3%) | 2 |
| Head injury | 2/32 (6.3%) | 2 |
| Investigations | ||
| Alanine aminotransferase increased | 8/32 (25%) | 8 |
| Aspartate aminotransferase increased | 6/32 (18.8%) | 6 |
| Blood creatinine increased | 2/32 (6.3%) | 2 |
| C-reactive protein increased | 2/32 (6.3%) | 2 |
| International normalised ratio increased | 2/32 (6.3%) | 2 |
| Protein total decreased | 2/32 (6.3%) | 2 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 22/32 (68.8%) | 22 |
| Hypokalaemia | 20/32 (62.5%) | 20 |
| Hypomagnesaemia | 9/32 (28.1%) | 9 |
| Hyphophosphataemia | 5/32 (15.6%) | 5 |
| Fluid Retention | 4/32 (12.5%) | 4 |
| Iron deficiency | 2/32 (6.3%) | 2 |
| Hyponatraemia | 2/32 (6.3%) | 2 |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 2/32 (6.3%) | 2 |
| Bone pain | 2/32 (6.3%) | 2 |
| Nervous system disorders | ||
| Headache | 13/32 (40.6%) | 13 |
| Lethargy | 2/32 (6.3%) | 2 |
| Sensory loss | 2/32 (6.3%) | 2 |
| Visual field defect | 2/32 (6.3%) | 2 |
| Dizziness | 2/32 (6.3%) | 2 |
| Dystonia | 2/32 (6.3%) | 2 |
| Speech disorder | 2/32 (6.3%) | 2 |
| Psychiatric disorders | ||
| Insomnia | 2/32 (6.3%) | 2 |
| Irritability | 2/32 (6.3%) | 2 |
| Enuresis | 3/32 (9.4%) | 3 |
| Agitation | 2/32 (6.3%) | 2 |
| Depression | 2/32 (6.3%) | 2 |
| Encopresis | 2/32 (6.3%) | 2 |
| Renal and urinary disorders | ||
| Dysuria | 2/32 (6.3%) | 2 |
| Urinary incontinence | 2/32 (6.3%) | 2 |
| Skin and subcutaneous tissue disorders | ||
| Alopecia | 23/32 (71.9%) | 23 |
| Pruritus | 7/32 (21.9%) | 7 |
| Rash | 6/32 (18.8%) | 6 |
| Skin Hyperpigmentation | 4/32 (12.5%) | 4 |
| Rash Maculo papular | 3/32 (9.4%) | 3 |
| Dermatitis diaper | 2/32 (6.3%) | 2 |
| Vascular disorders | ||
| Hypertension | 4/32 (12.5%) | 4 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Study Medical Director |
|---|---|
| Organization | bluebird bio, Inc |
| Phone | 339-499-9300 |
| medinfo@bluebirdbio.com |
- ALD-102
- 2011-001953-10