Trial Outcomes & Findings for A Study of the Efficacy and Safety of Hematopoietic Stem Cells Transduced With Lenti-D Lentiviral Vector for the Treatment of Cerebral Adrenoleukodystrophy (CALD) (NCT NCT01896102)

Last Updated: 2022-04-25

Results Overview

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months post-infusion; had not received rescue cell administration or allo-HSCT by 24 months post-infusion; and had not withdrawn from the study or had not been lost to follow-up by 24 months post-infusion.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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

32 participants

Primary outcome timeframe

At Month 24

Results posted on

2022-04-25

Participant Flow

This study was conducted at 8 centers from 21 August 2013 (first participants first visit) to 26 March 2021 (last participants last visit).

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.

Participant milestones

Participant milestones
Measure	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 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).
Overall Study STARTED	32
Overall Study COMPLETED	29
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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 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).
Overall Study Death	1
Overall Study Participant to receive allogenic transplant	2

Baseline Characteristics

A Study of the Efficacy and Safety of Hematopoietic Stem Cells Transduced With Lenti-D Lentiviral Vector for the Treatment of Cerebral Adrenoleukodystrophy (CALD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lenti-D Drug Product n=32 Participants 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.
Age, Continuous	6 years STANDARD_DEVIATION 2.4 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants
Race (NIH/OMB) More than one race	5 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: At Month 24

Population: 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).

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=32 Participants 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.
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	90.6 Percentage of participants Interval 75.0 to 98.0

PRIMARY outcome

Timeframe: By Month 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=32 Participants 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.
Proportion of Participants Who Had Experienced Either Acute ([>or=] Grade II) or Chronic Graft Versus Host Disease (GVHD) by Month 24	0.0 Percentage of participants Interval 0.0 to 10.9

SECONDARY outcome

Timeframe: At Month 24

Percentage of participants who demonstrated resolution of gadolinium positivity (i.e., GdE-) on MRI at Month 24 were reported.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=30 Participants 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.
Percentage of Participants Who Demonstrated Resolution of Gadolinium Positivity on Magnetic Resonance Imaging (MRI) at Month 24	86.7 Percentage of participants Interval 69.3 to 96.2

SECONDARY outcome

Timeframe: Up to Month 24

Population: 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.

Sustained resolution of gadolinium positivity was defined as having at least two consecutive GdE- results by MRI without a subsequent evaluation indicating GdE+.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=24 Participants 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.
Time to Sustained Resolution of Gadolinium Positivity on MRI	77 Days Interval 25.0 to 551.0

SECONDARY outcome

Timeframe: Baseline up to Month 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=30 Participants 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.
Number of Participants With Change in Total Neurologic Function Score (NFS) From Baseline up to Month 24	4 Participants

SECONDARY outcome

Timeframe: At 24 months after Lenti-D drug infusion

Population: TP consisted of participants who received Lenti-D Drug Product 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.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=32 Participants 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.
Major Functional Disability (MFD)-Free Survival Rate	90.6 Percentage of participants Interval 73.7 to 96.9

SECONDARY outcome

Timeframe: At 24 months after Lenti-D drug infusion

Population: TP consisted of participants who received Lenti-D Drug Product 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.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=32 Participants 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 Survival Rate	96.7 Percentage of participants Interval 78.6 to 99.5

SECONDARY outcome

Timeframe: By 42 days post-drug infusion

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=32 Participants 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.
Proportion of Participants With Neutrophil Engraftment by 42 Days Post-drug Product Infusion	100.0 Percentage of participants Interval 89.1 to 100.0

SECONDARY outcome

Timeframe: By 42 days post-drug infusion

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=32 Participants 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.
Time to Neutrophil Engraftment Post-drug Product Infusion	13.0 Days Interval 11.0 to 41.0

SECONDARY outcome

Timeframe: By Month 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=32 Participants 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.
Proportion of Participants With Platelet Engraftment by Month 24	100 Percentage of participants Interval 89.1 to 100.0

SECONDARY outcome

Timeframe: By Month 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=32 Participants 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.
Time to Platelet Engraftment Post-drug Product Infusion	32 Days Interval 16.0 to 60.0

SECONDARY outcome

Timeframe: By Month 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=29 Participants 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.
Proportion of Participants With Engraftment Failure By Month 24	0.0 Percentage of participants Interval 0.0 to 11.9

SECONDARY outcome

Timeframe: By Month 24

Population: 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.

Percentage of Participants who have undergone a subsequent allo-HSC infusion at Month 24 were reported.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=31 Participants 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.
Proportion of Participants Who Underwent a Subsequent Allo-Hematopoietic Stem Cell (HSC) Infusion by Month 24	6.5 Percentage of participants Interval 0.8 to 21.4

SECONDARY outcome

Timeframe: From time of drug product infusion through 100 and 365 days post-drug product infusion

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=32 Participants 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.
Percentage of Participants With Transplant-related Mortality Through 100 and 365 Days Post-drug Product Infusion Transplant-related mortality within 100 days	0.0 Percentage of participants Interval 0.0 to 10.9
Percentage of Participants With Transplant-related Mortality Through 100 and 365 Days Post-drug Product Infusion Transplant-related mortality within 365 days	0.0 Percentage of participants Interval 0.0 to 10.9

SECONDARY outcome

Timeframe: From date of informed consent up to Month 24

Population: ITT population consisted of participants who initiated any study procedures, beginning with mobilization by G-CSF

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.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=32 Participants 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.
Percentage of Participants With Adverse Events (AEs), Serious AEs, Grade >=3 AE, Related AEs, Related SAEs and Related Grade >=3 AEs Percentage of participants with at least 1 AE	100.0 Percentage of participants
Percentage of Participants With Adverse Events (AEs), Serious AEs, Grade >=3 AE, Related AEs, Related SAEs and Related Grade >=3 AEs Percentage of participants with at least 1 SAE	65.6 Percentage of participants
Percentage of Participants With Adverse Events (AEs), Serious AEs, Grade >=3 AE, Related AEs, Related SAEs and Related Grade >=3 AEs Percentage of participants with at least 1 AE related to Lenti-D Drug	9.4 Percentage of participants
Percentage of Participants With Adverse Events (AEs), Serious AEs, Grade >=3 AE, Related AEs, Related SAEs and Related Grade >=3 AEs Percentage of participants with at least 1 SAE related to Lenti-D Drug	3.1 Percentage of participants
Percentage of Participants With Adverse Events (AEs), Serious AEs, Grade >=3 AE, Related AEs, Related SAEs and Related Grade >=3 AEs Percentage of participants with at least 1 Grade >=3 AE	93.8 Percentage of participants
Percentage of Participants With Adverse Events (AEs), Serious AEs, Grade >=3 AE, Related AEs, Related SAEs and Related Grade >=3 AEs Percentage of participants with at least 1 Grade>=3 AE related to Lenti-D Drug	3.1 Percentage of participants

SECONDARY outcome

Timeframe: From time of drug product infusion up to Month 24

Population: ITT population consisted of participants who initiated any study procedures, beginning with mobilization by G-CSF.

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.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=32 Participants 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.
Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 Hematology: Leukocytes (<4.0 x 10^9/L)	100.0 Percentage of participants
Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 Hematology: Leukocytes (>=18 x 10^9/L)	0.0 Percentage of participants
Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 Hematology: Neutrophils (<1.0 x 10^9/L)	78.1 Percentage of participants
Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 Hematology: Erythrocytes (<=3.0 x 10^12/L)	43.8 Percentage of participants
Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 Hematology: Platelets (<=75 x 10^9/L)	96.9 Percentage of participants
Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 Chemistry: Sodium (<=126 mmol/L)	0.0 Percentage of participants
Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 Chemistry: Sodium (>=156 mmol/L)	0.0 Percentage of participants
Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 Chemistry: Potassium (<=3 mmol/L)	21.9 Percentage of participants
Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 Chemistry: Potassium (>=6 mmol/L)	0.0 Percentage of participants
Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 Chemistry: Glucose (<=3.0 mmol/L)	0.0 Percentage of participants
Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 Chemistry: Urea Nitrogen (>=10.7 mmol/L)	0.0 Percentage of participants
Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 Chemistry: Creatinine (>=150 umol/L)	0.0 Percentage of participants
Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 LFT: ALA (>=3 x ULN)	3.1 Percentage of participants
Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 LFT: ASA (>=3 x ULN)	3.1 Percentage of participants
Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 LFT: AP (>=3 x ULN)	0.0 Percentage of participants
Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 LFT: Bilirubin (>=34.2 umol/L)	0.0 Percentage of participants

SECONDARY outcome

Timeframe: From Post-Neutrophil Engraftment up to Month 24

Population: 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.

Number of emergency room visits (post-neutrophil engraftment) up to Month 24 were reported.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=32 Participants 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.
Number of Emergency Room Visits (Post-Neutrophil Engraftment) By Month 24	13 Emergency room visits

SECONDARY outcome

Timeframe: From post-neutrophil engraftment up to Month 24

Number of In-patient hospitalizations (post-neutrophil engraftment) by Month 24 were reported.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=32 Participants 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.
Number of In-patient Hospitalizations (Post-Neutrophil Engraftment) By Month 24	14 Hospitalizations

SECONDARY outcome

Timeframe: From post-neutrophil engraftment up to Month 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=14 Participants 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.
Duration of In-patient Hospitalizations (Post-Neutrophil Engraftment) up to Month 24	3.0 Days Interval 2.0 to 33.0

SECONDARY outcome

Timeframe: From post-neutrophil engraftment up to Month 24

Number of ICU Stays (Post-neutrophil Engraftment) By Month 24 were reported.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=32 Participants 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.
Number of Intensive Care Units (ICU) Stays (Post-neutrophil Engraftment) By Month 24	1 ICU Stays

SECONDARY outcome

Timeframe: From post-neutrophil engraftment up to Month 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=1 Participants 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.
Duration of ICU Stays (Post-neutrophil Engraftment) By Month 24	12.0 Days Interval 12.0 to 12.0

SECONDARY outcome

Timeframe: By Month 24

Population: TP consisted of participants who received Lenti-D Drug Product infusion.

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.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=32 Participants 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.
Number of Participants With Vector-Derived Replication Competent Lentivirus (RCL) Detected by Month 24	0 Participants

SECONDARY outcome

Timeframe: By Month 24

Population: TP consisted of participants who received Lenti-D Drug Product infusion.

Insertional oncogenesis including myelodysplasia, leukemia, lymphoma. Number of participants with insertional oncogenesis at Month 24 were reported.

Outcome measures

Outcome measures
Measure	Lenti-D Drug Product n=32 Participants 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.
Number of Participants With Insertional Oncogenesis By Month 24	0 Participants

Adverse Events

Lenti-D Drug Product

Serious events: 21 serious events

Other events: 32 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Lenti-D Drug Product n=32 participants at risk 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.
General disorders Pyrexia	18.8% 6/32 • Number of events 6 • From date of informed consent up to Month 24
Blood and lymphatic system disorders Febrile neutropenia	25.0% 8/32 • Number of events 8 • From date of informed consent up to Month 24
Cardiac disorders Cardio-respiratory arrest	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Endocrine disorders Adrenal insufficiency	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Gastrointestinal disorders Abdominal pain	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Gastrointestinal disorders Stomatitis	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Gastrointestinal disorders Vomiting	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Hepatobiliary disorders Acute hepatic failure	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Infections and infestations Vascular device infection	9.4% 3/32 • Number of events 3 • From date of informed consent up to Month 24
Infections and infestations Cystitis viral	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Infections and infestations Gastroenteritis	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Infections and infestations Influenza	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Infections and infestations Otitis media	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Infections and infestations Viral infection	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Infections and infestations Sinusitis	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Injury, poisoning and procedural complications Head injury	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Injury, poisoning and procedural complications Procedural Pain	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Injury, poisoning and procedural complications Spinal fracture	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Metabolism and nutrition disorders Decreased appetite	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Musculoskeletal and connective tissue disorders Rhabdomyolysis	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Nervous system disorders Dyskinesia	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Nervous system disorders Neurological decompensation	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Nervous system disorders Seizure	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Renal and urinary disorders Acute kidney injury	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24
Respiratory, thoracic and mediastinal disorders Respiratory distress	3.1% 1/32 • Number of events 1 • From date of informed consent up to Month 24

Other adverse events

Other adverse events
Measure	Lenti-D Drug Product n=32 participants at risk 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.
Blood and lymphatic system disorders Thrombocytopenia	96.9% 31/32 • Number of events 31 • From date of informed consent up to Month 24
Blood and lymphatic system disorders Anaemia	96.9% 31/32 • Number of events 31 • From date of informed consent up to Month 24
Blood and lymphatic system disorders Neutropenia	93.8% 30/32 • Number of events 30 • From date of informed consent up to Month 24
Blood and lymphatic system disorders Febrile neutropenia	62.5% 20/32 • Number of events 20 • From date of informed consent up to Month 24
Blood and lymphatic system disorders Leukopenia	34.4% 11/32 • Number of events 11 • From date of informed consent up to Month 24
Blood and lymphatic system disorders Lymphopenia	18.8% 6/32 • Number of events 6 • From date of informed consent up to Month 24
Cardiac disorders Bradycardia	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Cardiac disorders Tachycardia	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Cardiac disorders Sinus bradycardia	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Gastrointestinal disorders Nausea	93.8% 30/32 • Number of events 30 • From date of informed consent up to Month 24
Gastrointestinal disorders Vomiting	87.5% 28/32 • Number of events 28 • From date of informed consent up to Month 24
Gastrointestinal disorders Stomatitis	84.4% 27/32 • Number of events 27 • From date of informed consent up to Month 24
Gastrointestinal disorders Abdominal pain	53.1% 17/32 • Number of events 17 • From date of informed consent up to Month 24
Gastrointestinal disorders Diarrhoea	43.8% 14/32 • Number of events 14 • From date of informed consent up to Month 24
Gastrointestinal disorders Constipation	28.1% 9/32 • Number of events 9 • From date of informed consent up to Month 24
Gastrointestinal disorders Oral pain	9.4% 3/32 • Number of events 3 • From date of informed consent up to Month 24
Gastrointestinal disorders Proctitis	9.4% 3/32 • Number of events 3 • From date of informed consent up to Month 24
Gastrointestinal disorders Toothache	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
General disorders Pyrexia	34.4% 11/32 • Number of events 11 • From date of informed consent up to Month 24
General disorders Catheter site pain	25.0% 8/32 • Number of events 8 • From date of informed consent up to Month 24
General disorders Catheter site hemorrhage	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
General disorders Fatigue	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Infections and infestations Vascular device infection	9.4% 3/32 • Number of events 3 • From date of informed consent up to Month 24
Infections and infestations Enterobiasis	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Infections and infestations Oral candiasis	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Infections and infestations Rhinovirus infection	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Infections and infestations Viral infection	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Injury, poisoning and procedural complications Procedural Pain	21.9% 7/32 • Number of events 7 • From date of informed consent up to Month 24
Injury, poisoning and procedural complications Allergic transfusion reaction	12.5% 4/32 • Number of events 4 • From date of informed consent up to Month 24
Injury, poisoning and procedural complications Fall	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Injury, poisoning and procedural complications Head injury	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Investigations Alanine aminotransferase increased	25.0% 8/32 • Number of events 8 • From date of informed consent up to Month 24
Investigations Aspartate aminotransferase increased	18.8% 6/32 • Number of events 6 • From date of informed consent up to Month 24
Investigations Blood creatinine increased	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Investigations C-reactive protein increased	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Investigations International normalised ratio increased	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Investigations Protein total decreased	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Metabolism and nutrition disorders Decreased appetite	68.8% 22/32 • Number of events 22 • From date of informed consent up to Month 24
Metabolism and nutrition disorders Hypokalaemia	62.5% 20/32 • Number of events 20 • From date of informed consent up to Month 24
Metabolism and nutrition disorders Hypomagnesaemia	28.1% 9/32 • Number of events 9 • From date of informed consent up to Month 24
Metabolism and nutrition disorders Hyphophosphataemia	15.6% 5/32 • Number of events 5 • From date of informed consent up to Month 24
Metabolism and nutrition disorders Fluid Retention	12.5% 4/32 • Number of events 4 • From date of informed consent up to Month 24
Nervous system disorders Headache	40.6% 13/32 • Number of events 13 • From date of informed consent up to Month 24
Nervous system disorders Lethargy	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Nervous system disorders Sensory loss	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Nervous system disorders Visual field defect	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Psychiatric disorders Insomnia	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Psychiatric disorders Irritability	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Renal and urinary disorders Dysuria	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Skin and subcutaneous tissue disorders Alopecia	71.9% 23/32 • Number of events 23 • From date of informed consent up to Month 24
Skin and subcutaneous tissue disorders Pruritus	21.9% 7/32 • Number of events 7 • From date of informed consent up to Month 24
Skin and subcutaneous tissue disorders Rash	18.8% 6/32 • Number of events 6 • From date of informed consent up to Month 24
Skin and subcutaneous tissue disorders Skin Hyperpigmentation	12.5% 4/32 • Number of events 4 • From date of informed consent up to Month 24
Skin and subcutaneous tissue disorders Rash Maculo papular	9.4% 3/32 • Number of events 3 • From date of informed consent up to Month 24
Skin and subcutaneous tissue disorders Dermatitis diaper	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Vascular disorders Hypertension	12.5% 4/32 • Number of events 4 • From date of informed consent up to Month 24
Metabolism and nutrition disorders Iron deficiency	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Metabolism and nutrition disorders Hyponatraemia	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Musculoskeletal and connective tissue disorders Arthralgia	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Musculoskeletal and connective tissue disorders Bone pain	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Nervous system disorders Dizziness	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Nervous system disorders Dystonia	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Nervous system disorders Speech disorder	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Psychiatric disorders Enuresis	9.4% 3/32 • Number of events 3 • From date of informed consent up to Month 24
Psychiatric disorders Agitation	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Psychiatric disorders Depression	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Psychiatric disorders Encopresis	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24
Renal and urinary disorders Urinary incontinence	6.2% 2/32 • Number of events 2 • From date of informed consent up to Month 24

Additional Information

Study Medical Director

bluebird bio, Inc

Phone: 339-499-9300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER