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Autologous Cd34+ Haematopoietic Stem Cells Genetically Modified With Lentiviral Vector Encoding The Cd18 Gene

This article discusses a clinical trial investigating the long-term safety and effectiveness of a gene therapy treatment for Leukocyte Adhesion Deficiency-I (LAD-I). The study focuses on a drug called RP-L201, which uses genetically modified stem cells to treat this rare genetic disorder. Patients who previously participated in an earlier phase of the trial are being followed for up to 15 years to monitor the treatment’s long-term effects and potential benefits.

Table of Contents

What is Leukocyte Adhesion Deficiency-I (LAD-I)?

Leukocyte Adhesion Deficiency-I (LAD-I) is a rare genetic disorder that affects the immune system[1]. In this condition, white blood cells (leukocytes) are unable to move properly to sites of infection in the body. This leads to recurrent and severe infections, as well as other health problems.

What is RP-L201?

RP-L201, also known as LADICell, is an innovative gene therapy product designed to treat LAD-I[1]. It is classified as an advanced therapy medicinal product, specifically a gene therapy. RP-L201 is currently being studied in clinical trials to evaluate its safety and effectiveness in treating patients with LAD-I.

How Does RP-L201 Work?

RP-L201 works by using the patient’s own cells to correct the genetic defect causing LAD-I. Here’s a simplified explanation of the process:

  1. Cell collection: Doctors collect special blood-forming stem cells (called CD34+ hematopoietic stem cells) from the patient’s blood.
  2. Genetic modification: These cells are then modified in a laboratory using a lentiviral vector. This vector is a harmless virus that carries a correct copy of the ITGB2 gene, which is faulty in LAD-I patients.
  3. Cell infusion: The modified cells are then given back to the patient through an intravenous infusion.
  4. Cell regeneration: These modified cells can then produce new blood cells that have the correct gene, potentially correcting the LAD-I defect.

The ITGB2 gene provides instructions for making a protein called CD18, which is crucial for proper immune function[1]. By introducing a correct copy of this gene, RP-L201 aims to restore normal immune function in patients with LAD-I.

The Clinical Trial for RP-L201

A clinical trial is currently underway to evaluate the long-term safety and effectiveness of RP-L201 in patients with LAD-I[1]. This trial, known as a Long-Term Follow-Up (LTFU) study, is designed to monitor patients who have received RP-L201 treatment for up to 15 years after their initial treatment.

Who is Eligible for the Treatment?

The current long-term follow-up study is specifically for patients who have already received RP-L201 in a previous clinical trial. To be eligible, patients must[1]:

  • Have been enrolled in the Phase I/II parent study RP-L201-0318
  • Have received RP-L201 in that study
  • Be willing and able to follow the study visit schedule and other requirements
  • Provide informed consent to participate in the study

Safety and Efficacy Monitoring

The long-term follow-up study is designed to carefully monitor the safety and effectiveness of RP-L201 over time. Some key aspects being monitored include[1]:

  • Infections: Any significant infections that require hospitalization or intravenous antibiotics
  • LAD-I symptoms: Any new skin or oral lesions that might be caused by LAD-I
  • Side effects: Any late-occurring serious side effects that might be related to the treatment
  • Cancer risk: Any occurrence of cancer that might be related to the treatment
  • Treatment effectiveness: Whether the treatment continues to work over time
  • Graft-versus-host disease (GvHD): Any signs of this condition, which can occur after some types of cell therapies

Potential Benefits of RP-L201

While the long-term effects are still being studied, the potential benefits of RP-L201 for LAD-I patients may include[1]:

  • Reduction in the number and severity of infections
  • Fewer and shorter hospital stays due to infections
  • Improvement or resolution of LAD-I-related symptoms, such as skin rashes or gum problems
  • Normalization of white blood cell counts
  • Long-term presence of the corrected gene in the patient’s blood cells
  • Improved overall survival and quality of life

It’s important to note that RP-L201 is still an experimental treatment, and more research is needed to fully understand its long-term effects and benefits. Patients considering this treatment should discuss it thoroughly with their healthcare providers to understand the potential risks and benefits.

Aspect Details
Study Type Long-Term Follow-Up (LTFU) for Gene Therapy of Leukocyte Adhesion Deficiency-I (LAD-I)
Treatment RP-L201 (autologous CD34+ hematopoietic stem cells genetically modified with lentiviral vector encoding the CD18 gene)
Duration Up to 15 years post-infusion
Visit Schedule Every 6 months up to Year 5, then yearly until Year 15
Primary Objectives Evaluate long-term safety and efficacy of RP-L201
Key Endpoints Infection rates, skin/oral lesions, adverse events, malignancy, graft failure, GvHD, survival rates, CD18 expression
Eligibility Participants from previous Phase I/II study who received RP-L201

FAQ

  • What is Leukocyte Adhesion Deficiency-I (LAD-I)? Leukocyte Adhesion Deficiency-I (LAD-I) is a rare genetic disorder that affects the immune system. It causes white blood cells to have difficulty sticking to blood vessel walls, which is necessary for fighting infections. This can lead to severe and recurring infections in patients with LAD-I.
  • What is RP-L201 and how does it work? RP-L201 is a gene therapy treatment for LAD-I. It involves taking the patient's own blood stem cells, modifying them with a virus that carries a correct copy of the ITGB2 gene, and then infusing these modified cells back into the patient. This aims to provide the patient with functional white blood cells that can fight infections more effectively.
  • How long will patients be followed in this study? Patients will be followed for up to 15 years after receiving the RP-L201 treatment. Study visits will occur every 6 months up to Year 5 post-infusion, and then yearly until Year 15 post-infusion.
  • What are the main goals of this long-term follow-up study? The main goals are to evaluate the long-term safety of RP-L201 and to assess its long-term effectiveness in treating LAD-I. This includes monitoring for any side effects, checking if the treatment continues to work over time, and observing improvements in the patients' ability to fight infections.
  • Who is eligible to participate in this study? Participants must have been enrolled in the previous Phase I/II study (RP-L201-0318) and received the RP-L201 treatment. They must also be willing and able to follow the study visit schedule and provide informed consent to participate in this long-term follow-up study.

Ongoing Clinical Trials on Autologous Cd34+ Haematopoietic Stem Cells Genetically Modified With Lentiviral Vector Encoding The Cd18 Gene

  • Study on Long-Term Safety and Efficacy of Gene Therapy for Leukocyte Adhesion Deficiency-I Using RP-L201 in Patients with LAD-I

    Not recruiting

    1 1
    Investigated diseases:
    Investigated drugs:
    Spain

Glossary

  • Leukocyte Adhesion Deficiency-I (LAD-I): A rare genetic disorder affecting the immune system, where white blood cells have difficulty sticking to blood vessel walls, leading to severe and recurring infections.
  • Gene therapy: A treatment approach that involves modifying a person's genes to treat or cure a disease.
  • Autologous: Referring to cells or tissues obtained from the same individual. In this context, it means using the patient's own stem cells for treatment.
  • CD34+ hematopoietic stem cells: A type of blood-forming stem cell that can develop into various types of blood cells, including white blood cells.
  • Lentiviral vector: A modified virus used to deliver genetic material into cells for gene therapy purposes.
  • ITGB2 gene: The gene that provides instructions for making the CD18 protein, which is essential for proper immune cell function and is defective in LAD-I patients.
  • Vector Copy Number (VCN): A measure of how many copies of the therapeutic gene have been inserted into the patient's cells.
  • CD18 expression: The presence of the CD18 protein on the surface of cells, which is important for proper immune function.
  • Graft-versus-Host Disease (GvHD): A potential complication in some cell therapies where the transplanted cells attack the recipient's body.
  • Allogeneic HSCT: A type of stem cell transplant where the cells come from a donor, rather than the patient themselves.

References

  1. http://clinicaltrials.eu/trial/study-on-long-term-safety-and-efficacy-of-gene-therapy-for-leukocyte-adhesion-deficiency-i-using-rp-l201-in-patients-with-lad-i/