A Phase 3 interventional study of Lenti-D in Cerebral Adrenoleukodystrophy (CALD), sponsored by bluebird bio. Completed at 8 sites in 6 countries. Open to male participants aged Up to 17 Years. Per ClinicalTrials.gov, last updated 2024-05-24.
Sponsored by bluebird bio · Phase 3, Interventional, and Treatment
The purpose of this study is to evaluate the efficacy and safety of Lenti-D Drug Product (also known as elivaldogene autotemcel or Skysona, hereafter referred to as eli-cel) after myeloablative conditioning with busulfan and fludarabine in participants with CALD. A participant's blood stem cells will be 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 will be transplanted back into the participant following myeloablative conditioning. Enrollment and treatment in Study ALD-104 have been completed and further enrollment in this study is not expected, although participants follow-up remains ongoing in the long-term follow-up Study LTF-304 (NCT02698579).
68 studies on the registry are indexed under Adrenoleukodystrophy; 19 are open to participants now.
This study's enrollment of 35 is above the median of 31 across 40 interventional studies indexed under Adrenoleukodystrophy.
Browse Adrenoleukodystrophy studies →bluebird bio is the lead sponsor of 12 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Active CALD as defined by:
Exclusion Criteria:
Hematological compromise as evidenced by:
Hepatic compromise as evidenced by:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants received a single intravenous (IV) infusion of eli-cel (also referred to as Lenti-D Drug Product) on Day 1 at a dose of \> or = 5.0\*10\^6 CD34+ cells/kilogram (kg). All participants received myeloablative conditioning with busulfan and fludarabine over a number of days prior to drug product infusion.
Genetic: Lenti-D
Participants received a single IV infusion of Lenti-D Drug Product.
Also known as: elivaldogene autotemcel, eli-cel
Percentage of Participants Who Were Alive and Have None of the 6 Major Functional Disabilities (MFDs) at Month 24
The 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 defined as: alive at 24 months post infusion; have not developed any of the MFDs by 24 months post infusion; have not received rescue cell administration or allo-hematopoietic stem cell transplantation (HSCT) by 24 months post infusion; and have not withdrawn from the study or have not been lost to follow-up by 24 months post infusion.
Time frame: At Month 24
Percentage of Participants Who Achieved Neutrophil Engraftment After Drug Product Infusion
Neutrophil engraftment is defined as achieving 3 consecutive absolute neutrophil count (ANC) laboratory values of \>= 0.5x10\^9 cells/liter (L) (after initial post-infusion nadir) obtained on different days by 42 days postinfusion of eli-cel (Rel Day 43).
Time frame: By 42 days post-drug infusion
Percentage of Participants Without Gadolinium Enhancement (i.e. GdE-) on Magnetic Resonance Imaging (MRI) at Month 24
Percentage of participants without Gadolinium Enhancement (i.e. GdE-) on MRI at Month 24 were reported.
Time frame: At Month 24
Number of Participants With Change in Neurologic Function Score (NFS) From Baseline to Month 24
NFS was a 25-point score used to evaluate the severity of gross neurologic dysfunction in cerebral adrenoleukodystrophy (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 central nervous system (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"= absence of clinical signs of cerebral disease.
Time frame: Baseline up to Month 24
Number of Participants Who Achieved Stable NFS at Month 24
Stable NFS was defined as maintaining an NFS \<=4 without an increase of \>3 from Baseline. Number of participants who achieved stable NFS at Month 24 were reported.
Time frame: At Month 24
Major Functional Disability (MFD)-Free Survival Rate
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
Overall Survival Rate
Overall survival rate was defined as percentage of participants alive from date of Lenti-D drug product infusion (Day 1) to date of death of all causes. Overall survival rate was censored at the date of last visit if the subject were alive. Participants who are alive were censored at the date of last contact. Overall survival rate was analyzed using Kaplan-Meier Analysis.
Time frame: At 24 months after Lenti-D drug infusion
Median Detectable Vector Copy Number (VCN) in Peripheral Blood Cells by Month 6
Presence of vector sequences in the genome of cells derived from the originally transduced HSC indicates the presence of transduced cells amongst the HSC precursors. The presence of vector sequences was evaluated throughout the study in whole blood, in selected subpopulations of blood cells (including CD14+ cells), and in bone marrow when indicated. The presence of vector sequences in the genomic DNA of cells was detected using quantitative polymerase chain reaction (qPCR), and results were expressed as vector copy number (VCN; vector copies per diploid genome, c/dg).
Time frame: By Month 6 post-transplant
Time to Neutrophil Engraftment (NE) After Drug Product Infusion
Neutrophil engraftment is defined as achieving 3 consecutive absolute neutrophil count (ANC) laboratory values of \>= 0.5 x 10\^9 cells/liter (L) (after initial post-infusion nadir) obtained on different days by 42 days post-infusion of eli-cel (Rel Day 43). Time to neutrophil engraftment after drug product infusion was reported.
Time frame: By 42 days post-drug infusion
Percentage of Participants With Platelet Engraftment by Month 24
Platelet engraftment was defined as achieving 3 consecutive unsupported platelet counts of \>=20 x 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 x 10\^9 cells/L was considered the Day of platelet engraftment.
Time frame: By Month 24
Time to Platelet Engraftment Post-drug Product Infusion
Platelet Engraftment was defined as achieving 3 consecutive unsupported platelet counts of \> or =20 x 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 x 10\^9 cells/L was the day of PE. Time to platelet engraftment post-drug product infusion by Month 24 was reported.
Time frame: By Month 24
Percentage of Participants With Loss of Neutrophil Engraftment Post-drug Product Infusion 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 x 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 x 10\^9 cells/L was considered the day of secondary engraftment failure. Percentage of participants with both primary or secondary loss of neutrophil engraftment at Month 24 were reported.
Time frame: By Month 24
Percentage of Participants Who Underwent a Subsequent Allo- Hematopoietic Stem Cell Transplantation (HSCT) Infusion by Month 24
Percentage of participants who have undergone a subsequent allo-HSCT infusion by Month 24 were reported.
Time frame: By Month 24
Percentage of Participants Who Experienced Either Acute (>= Grade 2) or Chronic Graft Versus Host Disease (GVHD) at Month 24
Acute GVHD graded on the Acute GVHD Grading Scale (1-4): Grade 1 is characterized as mild disease, Grade 2 as moderate, Grade 3 as severe (involvement of any organ system), and Grade 4 as life-threatening; chronic GVHD was determined by the Investigator. GVHD was seen after an eli-cel participant received a subsequent allogeneic hematopoietic stem cell transplant. No GVHD was seen in participants who did not receive allogeneic stem cell transplants. Grade 2 non-serious GVHD was reported in a participant who received allogeneic transplant post eli-cel infusion. Percentage of participants who experienced either acute (\>= Grade 2) or chronic GVHD at Month 24 were reported.
Time frame: At Month 24
Percentage of Participants Who Experienced >= Grade 2 Acute Graft Versus Host Disease (GVHD) by Month 24
Acute GVHD graded on the Acute GVHD Grading Scale (1-4): Grade 1 is characterized as mild disease, Grade 2 as moderate, Grade 3 as severe (involvement of any organ system), and Grade 4 as life-threatening; Acute GVHD was determined by the Investigator. GVHD was seen after an eli-cel participant received a subsequent allogeneic hematopoietic stem cell transplant. No GVHD was seen in participants who did not receive allogeneic stem cell transplants. Grade 2 non-serious GVHD was reported in a participant who received allogeneic transplant post eli-cel infusion. Percentage of participants who experienced \>= Grade 2 Acute GVHD at Month 24 were reported.
Time frame: By Month 24
Percentage of Participants Who Experienced Chronic GVHD by Month 24
Chronic GVHD graded on the Chronic GVHD Grading Scale as limited or extensive. Chronic GVHD was determined by the Investigator. No chronic GVHD was observed in any participants. Acute GVHD was seen after an eli-cel participant received a subsequent allogeneic hematopoietic stem cell transplant. No GVHD was seen in participants who did not receive allogeneic stem cell transplants. Grade 2 non-serious GVHD was reported in a participant who received allogeneic transplant post eli-cel infusion. Percentage of participants who experienced chronic GVHD by Month 24 were reported.
Time frame: By Month 24
Percentage of Participants Who Experienced Transplant-related Mortality Through 100 and 365 Days Post-drug Product Infusion
Transplant-related mortality was determined by the investigator and summarized for the following intervals: from Rel Day 1 through 100 days post-drug product infusion (Rel Day 101) and from Rel Day 1 through 365 days post-drug product infusion (Rel Day 366). Percentage of participants who experienced 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
Percentage of Participants With Clinical >= Grade 3 Adverse Events (AEs), All Investigational Medicinal Product-related AEs, All Serious Adverse Events (SAEs), and >= Grade 3 Infections
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 subject and may require medical or surgical intervention to prevent an outcome listed previously. Percentage of participants with clinical \>= Grade 3 AEs, all investigational medicinal product-related AEs, all serious adverse events (SAEs), and \>= Grade 3 infections were reported.
Time frame: From date of informed consent up to Month 24
Number of Participants With >= Grade 3 Prolonged Cytopenia on or After Rel Day 60 And Rel Day 100
Number of participants with \>= Grade 3 prolonged cytopenia (i.e., decreased platelet counts, decreased neutrophil counts, and/or decreased hemoglobin counts) on or after Rel Day 60 and Rel Day 100 were reported.
Time frame: Prolonged cytopenias occurring on or after Rel Day 60 and Rel Day 100 following drug product infusion
Percentage of Participants With Potentially Clinically Significant Changes in Laboratory Parameters by Month 24
Laboratory parameters included Hematology (Leukocytes \[with a threshold range \<4.0 x 10\^9/L, \>=18 x 10\^9/L\], 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 \[\<=3.0 mmol/L\]), Renal (Urea Nitrogen \[\>=10.7 mmol/L\], Creatinine \[\>=150 umol/L\]) and liver (Alanine Aminotransferase \[ALA\]. Aspartate Aminotransferase \[ASA\], Alkaline Phosphatase \[AP\] with threshold 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 Day 1 to Month 24
Number of Emergency Room Visits (Post-Neutrophil Engraftment) by Month 24
Number of emergency room visits (post-neutrophil engraftment) up to Month 24 were reported.
Time frame: From Post-Neutrophil Engraftment up to Month 24
Median Number of Emergency Room Visits (Post-Neutrophil Engraftment) by Month 24
Median number of emergency room visits (post-neutrophil engraftment) up to Month 24 were reported.
Time frame: From Post-Neutrophil Engraftment up to Month 24
Number of In-patient Hospitalizations (Post-Neutrophil Engraftment) by Month 24
Number of In-patient hospitalizations (post-neutrophil engraftment) by Month 24 were reported.
Time frame: From Post-Neutrophil Engraftment up to Month 24
Median Number of In-patient Hospitalizations (Post-Neutrophil Engraftment) by Month 24
Median number of In-patient hospitalizations (post-neutrophil engraftment) by Month 24 were reported.
Time frame: From post-neutrophil engraftment up to Month 24
Duration of In-patient Hospitalizations (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. The range of in-patient hospitalizations is influenced by hospital stays for participants who received allogeneic stem cell transplants.
Time frame: From post-neutrophil engraftment up to Month 24
Number of Intensive Care Units (ICU) Stays (Post-neutrophil Engraftment) by Month 24
Number of ICU Stays (Post-neutrophil Engraftment) By Month 24 were reported.
Time frame: From post-neutrophil engraftment up to Month 24
Duration of ICU Stays (Post-neutrophil Engraftment) by 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.
Time frame: From post-neutrophil engraftment up to Month 24
Number of Participants Who Tested Positive and Negative for Vector-Derived Replication Competent Lentivirus (RCL) Detected by Month 24
Number of participants who tested positive and negative for vector-derived RCL detected at Month 24 were reported. Screening of participant's 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
Number of Participants With Insertional Oncogenesis by Month 24
Insertional oncogenesis included myelodysplastic syndrome, leukemia, lymphoma. Number of participants with insertional oncogenesis at Month 24 were reported.
Time frame: By Month 24 post-transplant
This study was conducted at 8 study centers in France, Italy, Germany, the Netherlands, United Kingdom, and United States of America from 24 January 2019 to 24 July 2023.
| Milestone | Lenti-D Drug Product |
|---|---|
| Started | 35 |
| Completed | 35 |
| Not completed | 0 |
The 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 defined as: alive at 24 months post infusion; have not developed any of the MFDs by 24 months post infusion; have not received rescue cell administration or allo-hematopoietic stem cell transplantation (HSCT) by 24 months post infusion; and have not withdrawn from the study or have not been lost to follow-up by 24 months post infusion.
| Percentage of participants | Lenti-D Drug Product |
|---|---|
| Percentage of Participants Who Were Alive and Have None of the 6 Major Functional Disabilities (MFDs) at Month 24 | 85.7 (69.7 to 95.2) |
Neutrophil engraftment is defined as achieving 3 consecutive absolute neutrophil count (ANC) laboratory values of \>= 0.5x10\^9 cells/liter (L) (after initial post-infusion nadir) obtained on different days by 42 days postinfusion of eli-cel (Rel Day 43).
| Percentage of participants | Lenti-D Drug Product |
|---|---|
| Percentage of Participants Who Achieved Neutrophil Engraftment After Drug Product Infusion | 100.0 (90.0 to 100.0) |
Percentage of participants without Gadolinium Enhancement (i.e. GdE-) on MRI at Month 24 were reported.
| Percentage of participants | Lenti-D Drug Product |
|---|---|
| Percentage of Participants Without Gadolinium Enhancement (i.e. GdE-) on Magnetic Resonance Imaging (MRI) at Month 24 | 94.3 (80.8 to 99.3) |
NFS was a 25-point score used to evaluate the severity of gross neurologic dysfunction in cerebral adrenoleukodystrophy (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 central nervous system (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"= absence of clinical signs of cerebral disease.
| Participants | Lenti-D Drug Product |
|---|---|
| Change at Month 24: Increased <=3 | 4 |
| Change at Month 24: Increased > 3 | 2 |
Stable NFS was defined as maintaining an NFS \<=4 without an increase of \>3 from Baseline. Number of participants who achieved stable NFS at Month 24 were reported.
| Participants | Lenti-D Drug Product |
|---|---|
| Number of Participants Who Achieved Stable NFS at Month 24 | 33 |
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.
| Percentage of participants | Lenti-D Drug Product |
|---|---|
| Major Functional Disability (MFD)-Free Survival Rate | 88.6 (72.4 to 95.5) |
Overall survival rate was defined as percentage of participants alive from date of Lenti-D drug product infusion (Day 1) to date of death of all causes. Overall survival rate was censored at the date of last visit if the subject were alive. Participants who are alive were censored at the date of last contact. Overall survival rate was analyzed using Kaplan-Meier Analysis.
| Percentage of participants | Lenti-D Drug Product |
|---|---|
| Overall Survival Rate | 100.0 (100.0 to 100.0) |
Presence of vector sequences in the genome of cells derived from the originally transduced HSC indicates the presence of transduced cells amongst the HSC precursors. The presence of vector sequences was evaluated throughout the study in whole blood, in selected subpopulations of blood cells (including CD14+ cells), and in bone marrow when indicated. The presence of vector sequences in the genomic DNA of cells was detected using quantitative polymerase chain reaction (qPCR), and results were expressed as vector copy number (VCN; vector copies per diploid genome, c/dg).
| copies per diploid genome (c/dg) | Lenti-D Drug Product |
|---|---|
| Median Detectable Vector Copy Number (VCN) in Peripheral Blood Cells by Month 6 | 1.05 (0.03 to 3.13) |
Neutrophil engraftment is defined as achieving 3 consecutive absolute neutrophil count (ANC) laboratory values of \>= 0.5 x 10\^9 cells/liter (L) (after initial post-infusion nadir) obtained on different days by 42 days post-infusion of eli-cel (Rel Day 43). Time to neutrophil engraftment after drug product infusion was reported.
| Days | Lenti-D Drug Product |
|---|---|
| Time to Neutrophil Engraftment (NE) After Drug Product Infusion | 14.0 (12 to 31) |
Platelet engraftment was defined as achieving 3 consecutive unsupported platelet counts of \>=20 x 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 x 10\^9 cells/L was considered the Day of platelet engraftment.
| Percentage of participants | Lenti-D Drug Product |
|---|---|
| Percentage of Participants With Platelet Engraftment by Month 24 | 100.0 (90.0 to 100.0) |
Platelet Engraftment was defined as achieving 3 consecutive unsupported platelet counts of \> or =20 x 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 x 10\^9 cells/L was the day of PE. Time to platelet engraftment post-drug product infusion by Month 24 was reported.
| Days | Lenti-D Drug Product |
|---|---|
| Time to Platelet Engraftment Post-drug Product Infusion | 29.0 (14 to 108) |
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 x 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 x 10\^9 cells/L was considered the day of secondary engraftment failure. Percentage of participants with both primary or secondary loss of neutrophil engraftment at Month 24 were reported.
| Percentage of participants | Lenti-D Drug Product |
|---|---|
| Percentage of Participants With Loss of Neutrophil Engraftment Post-drug Product Infusion by Month 24 | 0 (0.0 to 10.0) |
Percentage of participants who have undergone a subsequent allo-HSCT infusion by Month 24 were reported.
| Percentage of participants | Lenti-D Drug Product |
|---|---|
| Percentage of Participants Who Underwent a Subsequent Allo- Hematopoietic Stem Cell Transplantation (HSCT) Infusion by Month 24 | 8.6 (1.8 to 23.1) |
Acute GVHD graded on the Acute GVHD Grading Scale (1-4): Grade 1 is characterized as mild disease, Grade 2 as moderate, Grade 3 as severe (involvement of any organ system), and Grade 4 as life-threatening; chronic GVHD was determined by the Investigator. GVHD was seen after an eli-cel participant received a subsequent allogeneic hematopoietic stem cell transplant. No GVHD was seen in participants who did not receive allogeneic stem cell transplants. Grade 2 non-serious GVHD was reported in a participant who received allogeneic transplant post eli-cel infusion. Percentage of participants who experienced either acute (\>= Grade 2) or chronic GVHD at Month 24 were reported.
| Percentage of participants | Lenti-D Drug Product |
|---|---|
| Percentage of Participants Who Experienced Either Acute (>= Grade 2) or Chronic Graft Versus Host Disease (GVHD) at Month 24 | 2.9 (0.1 to 14.9) |
Acute GVHD graded on the Acute GVHD Grading Scale (1-4): Grade 1 is characterized as mild disease, Grade 2 as moderate, Grade 3 as severe (involvement of any organ system), and Grade 4 as life-threatening; Acute GVHD was determined by the Investigator. GVHD was seen after an eli-cel participant received a subsequent allogeneic hematopoietic stem cell transplant. No GVHD was seen in participants who did not receive allogeneic stem cell transplants. Grade 2 non-serious GVHD was reported in a participant who received allogeneic transplant post eli-cel infusion. Percentage of participants who experienced \>= Grade 2 Acute GVHD at Month 24 were reported.
| Percentage of participants | Lenti-D Drug Product |
|---|---|
| Percentage of Participants Who Experienced >= Grade 2 Acute Graft Versus Host Disease (GVHD) by Month 24 | 2.9 (0.1 to 14.9) |
Chronic GVHD graded on the Chronic GVHD Grading Scale as limited or extensive. Chronic GVHD was determined by the Investigator. No chronic GVHD was observed in any participants. Acute GVHD was seen after an eli-cel participant received a subsequent allogeneic hematopoietic stem cell transplant. No GVHD was seen in participants who did not receive allogeneic stem cell transplants. Grade 2 non-serious GVHD was reported in a participant who received allogeneic transplant post eli-cel infusion. Percentage of participants who experienced chronic GVHD by Month 24 were reported.
| Percentage of participants | Lenti-D Drug Product |
|---|---|
| Percentage of Participants Who Experienced Chronic GVHD by Month 24 | 0 (0.0 to 10.0) |
Transplant-related mortality was determined by the investigator and summarized for the following intervals: from Rel Day 1 through 100 days post-drug product infusion (Rel Day 101) and from Rel Day 1 through 365 days post-drug product infusion (Rel Day 366). Percentage of participants who experienced transplant-related mortality through 100 and 365 days post-drug product infusion were reported.
| Percentage of participants | Lenti-D Drug Product |
|---|---|
| Transplant related mortality within 100 days | 0 (0.0 to 10.0) |
| Transplant related mortality within 365 days | 0 (0.0 to 10.0) |
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 subject and may require medical or surgical intervention to prevent an outcome listed previously. Percentage of participants with clinical \>= Grade 3 AEs, all investigational medicinal product-related AEs, all serious adverse events (SAEs), and \>= Grade 3 infections were reported.
| Percentage of participants | Lenti-D Drug Product |
|---|---|
| Participants with at least 1 >= Grade 3 AE | 100.0 |
| Participants with at least 1 AE related to Eli-cel | 20.0 |
| Participants with at least 1 SAE | 62.9 |
| Participants with >= Grade 3 infections | 28.6 |
Number of participants with \>= Grade 3 prolonged cytopenia (i.e., decreased platelet counts, decreased neutrophil counts, and/or decreased hemoglobin counts) on or after Rel Day 60 and Rel Day 100 were reported.
| Participants | Lenti-D Drug Product |
|---|---|
| On or after Rel Day 60 | 14 |
| On or after Rel Day 100 | 7 |
Laboratory parameters included Hematology (Leukocytes \[with a threshold range \<4.0 x 10\^9/L, \>=18 x 10\^9/L\], 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 \[\<=3.0 mmol/L\]), Renal (Urea Nitrogen \[\>=10.7 mmol/L\], Creatinine \[\>=150 umol/L\]) and liver (Alanine Aminotransferase \[ALA\]. Aspartate Aminotransferase \[ASA\], Alkaline Phosphatase \[AP\] with threshold range of \>=3 x upper limit of normal (ULN), Bilirubin \[\>=34.2 micromoles per liter (umol/L)\]). Clinical significance was decided by investigator.
| Percentage of participants | Lenti-D Drug Product |
|---|---|
| Hematology: Leukocytes (<4.0 x 10^9/L) | 100.0 |
| Hematology: Leukocytes (>=18 x 10^9/L) | 2.9 |
| Hematology: Neutrophils (<1.0 x 10^9/L) | 97.1 |
| Hematology: Erythrocytes (<=3.0 x 10^12/L) | 71.4 |
| Hematology: Platelets (<=75 x 10^9/L) | 100.0 |
| Hematology: Hemoglobin (<=8.0 g/dL) | 77.1 |
| Liver: ALA (>=3 x ULN) | 11.4 |
| Liver: ASA (>=3 x ULN) | 5.7 |
| Liver: AP (>=3 x ULN) | 0.0 |
| Liver: Bilirubin (>=34.2 umol/L) | 0.0 |
| Renal: Urea Nitrogen (>=10.7 mmol/L) | 0.0 |
| Renal: Creatinine (>=150 umol/L) | 0.0 |
| Chemistry: Sodium (<=126 mmol/L) | 0.0 |
| Chemistry: Sodium (>=156 mmol/L) | 0.0 |
| Chemistry: Potassium (<=3 mmol/L) | 25.7 |
| Chemistry: Potassium (>=6 mmol/L) | 0.0 |
| Chemistry: Glucose (<=3.0 mmol/L) | 0.0 |
Number of emergency room visits (post-neutrophil engraftment) up to Month 24 were reported.
| Emergency room visits | Lenti-D Drug Product |
|---|---|
| Number of Emergency Room Visits (Post-Neutrophil Engraftment) by Month 24 | 9 |
Median number of emergency room visits (post-neutrophil engraftment) up to Month 24 were reported.
| Median number of emergency room visits | Lenti-D Drug Product |
|---|---|
| Median Number of Emergency Room Visits (Post-Neutrophil Engraftment) by Month 24 | 1.0 (1 to 4) |
Number of In-patient hospitalizations (post-neutrophil engraftment) by Month 24 were reported.
| Hospitalizations | Lenti-D Drug Product |
|---|---|
| Number of In-patient Hospitalizations (Post-Neutrophil Engraftment) by Month 24 | 17 |
Median number of In-patient hospitalizations (post-neutrophil engraftment) by Month 24 were reported.
| Median number of hospitalization | Lenti-D Drug Product |
|---|---|
| Median Number of In-patient Hospitalizations (Post-Neutrophil Engraftment) by Month 24 | 1.0 (1 to 4) |
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. The range of in-patient hospitalizations is influenced by hospital stays for participants who received allogeneic stem cell transplants.
| Days | Lenti-D Drug Product |
|---|---|
| Duration of In-patient Hospitalizations (Post-Neutrophil Engraftment) up to Month 24 | 4.0 (2 to 56) |
Number of ICU Stays (Post-neutrophil Engraftment) By Month 24 were reported.
| ICU Stays | Lenti-D Drug Product |
|---|---|
| Number of Intensive Care Units (ICU) Stays (Post-neutrophil Engraftment) by Month 24 | 0 |
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.
No measurements were reported for this outcome.
Number of participants who tested positive and negative for vector-derived RCL detected at Month 24 were reported. Screening of participant's 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.
| Participants | Lenti-D Drug Product |
|---|---|
| Participants tested positive for RCL | 0 |
| Participants tested negative for RCL | 35 |
Insertional oncogenesis included myelodysplastic syndrome, leukemia, lymphoma. Number of participants with insertional oncogenesis at Month 24 were reported.
| Participants | Lenti-D Drug Product |
|---|---|
| Number of Participants With Insertional Oncogenesis by Month 24 | 1 |
Collected over From date of informed consent up to Month 24. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Lenti-D Drug Product | 0/35 (0%) | 22/35 (62.9%) | 35/35 (100%) |
| Event | Lenti-D Drug Product |
|---|---|
| PyrexiaGeneral disorders | 5/35 |
| Febrile neutropeniaBlood and lymphatic system disorders | 4/35 |
| Neurological decompensationNervous system disorders | 2/35 |
| PancytopeniaBlood and lymphatic system disorders | 2/35 |
| Disease progressionGeneral disorders | 2/35 |
| Pseudomonal bacteraemiaInfections and infestations | 2/35 |
| Transaminases increasedInvestigations | 1/35 |
| Myelodysplastic syndromeNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/35 |
| Anaphylactic transfusion reactionInjury, poisoning and procedural complications | 1/35 |
| Cytogenetic abnormalityCongenital, familial and genetic disorders | 1/35 |
| Event | Lenti-D Drug Product |
|---|---|
| ThrombocytopeniaBlood and lymphatic system disorders | 34/35 |
| StomatitisGastrointestinal disorders | 34/35 |
| AnaemiaBlood and lymphatic system disorders | 29/35 |
| NeutropeniaBlood and lymphatic system disorders | 29/35 |
| NauseaGastrointestinal disorders | 28/35 |
| VomitingGastrointestinal disorders | 26/35 |
| AlopeciaSkin and subcutaneous tissue disorders | 25/35 |
| Decreased appetiteMetabolism and nutrition disorders | 22/35 |
| ConstipationGastrointestinal disorders | 20/35 |
| Febrile neutropeniaBlood and lymphatic system disorders | 19/35 |
Transplant Population (TP) consisted of participants who received Lenti-D Drug Product infusion.
| Age, Continuous(years) | Lenti-D Drug Product |
|---|---|
| Mean | 7 ± 2.1 |
| Sex: Female, Male(Participants) | Lenti-D Drug Product |
|---|---|
| Female | 0 |
| Male | 35 |
| Ethnicity (NIH/OMB)(Participants) | Lenti-D Drug Product |
|---|---|
| Hispanic or Latino | 5 |
| Not Hispanic or Latino | 24 |
| Unknown or Not Reported | 6 |
| Race (NIH/OMB)(Participants) | Lenti-D Drug Product |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 2 |
| White | 21 |
| More than one race | 0 |
| Unknown or Not Reported | 12 |
PDFs hosted by the registry, ClinicalTrials.gov.
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