Lenti-D for Adrenoleukodystrophy

Phase-Based Progress Estimates
2
Effectiveness
3
Safety
UCL-ICH/Great Ormond Street Hospital, London, United Kingdom
Adrenoleukodystrophy+1 More
Lenti-D - Genetic
Eligibility
< 18
Male
Eligible conditions
Select

Study Summary

A Clinical Study to Assess the Efficacy and Safety of Gene Therapy for the Treatment of Cerebral Adrenoleukodystrophy (CALD)

See full description

Eligible Conditions

  • Adrenoleukodystrophy
  • Cerebral Adrenoleukodystrophy (CALD)

Treatment Effectiveness

Effectiveness Progress

2 of 3
This is further along than 85% of similar trials

Other trials for Adrenoleukodystrophy

Study Objectives

This trial is evaluating whether Lenti-D will improve 2 primary outcomes and 31 secondary outcomes in patients with Adrenoleukodystrophy. Measurement will happen over the course of 42 days post-drug product infusion.

Day 42
Percentage of Participants with Neutrophil Engraftment After Drug Product Infusion
Time to Neutrophil Engraftment Post-drug Product Infusion
Month 24
Change in Total Neurologic Function Score (NFS) From Baseline to Protocol Scheduled Visits
Value and Change in Total Neurologic Function Score (NFS) From Baseline to Protocol Scheduled Visits
Month 24
Percentage of Participants with Loss of Neutrophil Engraftment Post-drug Product Infusion by Month 24
Percentage of Participants with Platelet Engraftment by Month 24
Month 24 post-transplant
Duration of Intensive Care Units (ICU) Stays (Post-neutrophil Engraftment) by Month 24
Duration of Intensive Care Units (ICU) Stays (post-neutrophil engraftment) by Month 24
Duration of in-patient Hospitalizations (Post-Neutrophil Engraftment) by Month 24
Number of Emergency Room Visits (Post-Neutrophil Engraftment) by Month 24
Number of Intensive Care Units (ICU) Stays (Post-neutrophil Engraftment) by Month 24
Number of Intensive Care Units (ICU) Stays (post-neutrophil engraftment) by Month 24
Number of Participants in Which Vector-Derived Replication Competent Lentivirus (RCL) is Detected by Month 24
Number of Participants in which Vector-Derived Replication Competent Lentivirus (RCL) is Detected by Month 24
Number of Participants with Insertional Oncogenesis by Month 24
Number of in-patient Hospitalizations (Post-Neutrophil Engraftment) by Month 24
Percentage of Participants Without Gadolinium Enhancement (GdE) at Month 24
Percentage of Participants who Experience Chronic GVHD by Month 24
Percentage of Participants who Experience Either Acute (Greater Than or Equal to [> or =] Grade II) or Chronic Grafts Versus Host Disease (GVHD) at Month 24
Percentage of Participants who Experience Greater Than or Equal to (> or =) Grade II Acute GVHD by Month 24
Percentage of Participants who Experience Greater Than or Equal to (>or=) Grade II Acute GVHD by Month 24
Percentage of Participants who Undergo a Subsequent Hematopoietic Stem Cell (HSC) Infusion by Month 24
Percentage of Participants who are Alive and Have None of the 6 Major Functional Disabilities (MFDs) at Month 24
Percentage of Participants who experience either acute (Greater Than or Equal to [>or=] Grade II) or chronic Grafts versus Host Disease (GVHD) at Month 24
Percentage of Participants with Adverse Events (AEs) in Selected Categories
Percentage of Participants with Potentially Clinically Significant Changes in Laboratory Parameters by Month 24
Month 6 post-transplant
Detectable Vector Copy Number (VCN) in Peripheral Blood Cells by Month 6
Detectable vector copy number (VCN) in peripheral blood cells by Month 6
Day 365
Percentage of Participants who Experience Transplant-Related Mortality Through 100 and 365 days Post-drug Product Infusion
Percentage of Participants who Experience Transplant-Related Mortality Through 100 and 365 days post-drug product infusion
Month 24
Major Functional Disability (MFD)-Free Survival Over Time
Overall Survival
Month 24
Time to Platelet Engraftment Post-drug Product Infusion

Trial Safety

Safety Progress

3 of 3
This is further along than 85% of similar trials

Other trials for Adrenoleukodystrophy

Trial Design

1 Treatment Group

Lenti-D Drug Product
1 of 1
Experimental Treatment

This trial requires 35 total participants across 1 different treatment group

This trial involves a single treatment. Lenti-D is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase 3 and have had some early promising results.

Lenti-D Drug Product
Genetic
Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of > or = 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) following myeloablative conditioning with busulfan and fludarabine on Day 1.

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: up to month 24 (+or- 1 month) post-transplant
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly up to month 24 (+or- 1 month) post-transplant for reporting.

Closest Location

University of Minnesota - Minneapolis, MN

Eligibility Criteria

This trial is for male patients aged 18 and younger. There are 6 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
Informed consent is obtained from a competent custodial parent or guardian with legal capacity to execute a local Institutional Review Board (IRB)/independent ethics committee (IEC) approved consent. show original
Males aged 17 years and younger, at the time of parental/guardian consent and, where appropriate, participant assent.
Active central nervous system (CNS) disease established by central radiographic review of brain MRI demonstrating abnormalities in the brain. show original
i. Loes score between 0.5 and 9 (inclusive) on the 34-point scale, and ii. Gadolinium enhancement on MRI of demyelinating lesions.
NFS < or = 1.
You have elevated very long chain fatty acids (VLCFA) values. show original

Patient Q&A Section

What causes adrenoleukodystrophy?

"Adenoleukodystrophy type I has been reported in a family of nine from Japan. Our patient, his mother, his sister (a carrier), and daughter had mutations in CLDN1. Since only a small minority of the patients in these families were of consanguineous ancestry, this genetic factor does not seem to explain the occurrence of this disease. We suspect an environmental cause, as we witnessed a marked increase in ALD in a region where many people are engaged in agricultural activities." - Anonymous Online Contributor

Unverified Answer

How many people get adrenoleukodystrophy a year in the United States?

"About 2.5 million US children are diagnosed with ALD every year. In 2010, the United States spent $4.4 billion per year on treatment for ALD patients. In a recent study, findings suggests that there are at least 20,000 new cases of ALD every year occurring in the United States." - Anonymous Online Contributor

Unverified Answer

What is adrenoleukodystrophy?

"AdLD (also known as Adrenoleukodystrophy) is one of four genetically separable disorders within the leukodystrophy (white matter) group of disorders, which collectively are also referred to as leukodystrophies. All four disorders result in the absence of a critical type of white matter. This missing structure disturbs the formation of long-range connections of white matter fibers and causes white matter problems throughout the brain. Affected children are usually born with progressive white matter problems over time. These involve enlargement of the white matter and diffuse damage to myelin sheaths. This damage causes a progressive loss of nerve cell function. Over the next 10 years, the brain slowly stops making normal myelin." - Anonymous Online Contributor

Unverified Answer

What are the signs of adrenoleukodystrophy?

"[This signs and symptoms of children can be very similar to the physical symptoms they are displaying. Also, children who are diagnosed with AdLD can have a variety of symptoms, even when their test result is normal.] [This article is an expanded and revised version of a page with the same title in the previous edition of the textbook, The Child Neurology Atlas, Springer, 2014, ed. Hirsch, pp. 89–90]." - Anonymous Online Contributor

Unverified Answer

What are common treatments for adrenoleukodystrophy?

"A variety of treatments are used to manage the symptoms of ALD, although none is an antidote. A large variability in clinical features exists, in addition to a marked genetic heterogeneity among individuals with ALD. No medication has been approved by the US Food and Drug Administration for ALD treatments." - Anonymous Online Contributor

Unverified Answer

Can adrenoleukodystrophy be cured?

"It is possible to induce a clinical remission of a lethal X-linked recessive AAHD phenotype in some affected children. The patient should always be kept under close medical and nutritional surveillance and the long-term prognosis remains uncertain." - Anonymous Online Contributor

Unverified Answer

Is lenti-d typically used in combination with any other treatments?

"In most clinical trials, lentiviral vector was used in combination with other treatments [and was not used alone, indicating that the data are limited to a subgroup of patients who would be able to use a lentiviral vector in conjunction with other therapy(s)]. In most of the trials, no lentiviral vector alone was used. Most clinical trials used a lentiviral vector as monotherapy, and results of those trials may not reflect a general population of patients." - Anonymous Online Contributor

Unverified Answer

Has lenti-d proven to be more effective than a placebo?

"Compared with a placebo, both lenti-AAV and lenti-PEI improved the myelination of the distal spinal cord neurons. However, the efficacy and efficacy of lenti-AAV and lenti-PEI were not statistically different. These studies suggest that in order to evaluate the role of viral methods, larger studies are needed." - Anonymous Online Contributor

Unverified Answer

What is the latest research for adrenoleukodystrophy?

"The role of inflammatory cytokines in the pathogenesis of aLD has been documented in many animal studies. An emphasis remains on the need to identify if immune pathways are involved in the pathogenesis of aLD and whether this can be targeted in order to minimize the destructive effects of the disease. The role of genetic factors in this disease process and the identification of genes, which are important in the pathogenesis of the disease, continues to be an area of active research." - Anonymous Online Contributor

Unverified Answer

Have there been other clinical trials involving lenti-d?

"The first clinical trial involving lenti-d was reported in a 2011 publication. This clinical trial demonstrated increased survival, however without improvement in cognitive or motor function. There were no changes in inflammatory markers or markers of oxidative stress. There is interest in developing lenti-d to treat other neurodegenerative diseases, although additional clinical trials may be required before clinical application. Clinical trials involve a large investment of time and money and participation by patients. To obtain information about clinical trials, enrolling in lenti-d trials may be a worthwhile investment." - Anonymous Online Contributor

Unverified Answer

What does lenti-d usually treat?

"The lentivirus has been used to treat multiple diseases, including cancers, diabetes, and HIV. Some drugs on the market have been approved by the FDA or European Medicines Agency using lentivirus as a method to safely and effectively deliver therapeutic molecules, including anti-HIV and anti-cancer agents, into target cells. The use of lentivirus as a vehicle to deliver therapeutic molecules to target cells has expanded since the introduction of lentiviral vectors and has the potential to reduce the risks associated with conventional gene therapy methods. However, it is important to understand the mechanisms of action of lentivirus before this technology can be used to advance therapies for a wide range of diseases and conditions." - Anonymous Online Contributor

Unverified Answer

What is the average age someone gets adrenoleukodystrophy?

"The average age someone is diagnosed with ALD is 7.9 years old. answer: The average age someone is diagnosed with ALD for is 7.9 years old, although its actual age could be a little bit higher. It's recommended that the first blood tests are performed when a person is 4 or 5 years old. If not performed, it's recommended the blood tests are repeated yearly. The cause of this disease is hereditary transmission and can have several forms. There are many forms of this disease, [cervical spinal muscular atrophy (CIMA) (http://omim." - Anonymous Online Contributor

Unverified Answer
Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.
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