Longterm Follow-up of Subjects With Cerebral Adrenoleukodystrophy Who Were Treated With Lenti-D Drug Product

To overcome the limitations of allogeneic hematopoietic stem cell
transplantation (allo-HSCT), bluebird bio has developed a hematopoietic stem
cell (HSC) gene therapy strategy aiming to perform autologous transplantation
of cells that have been transduced ex vivo with an LVV that encodes for a
functional gene product.

Subjects who receive eli-cel in Study ALD-102 or Study ALD-104 are initially
followed for approximately 2 years post-drug product infusion under their
respective parent study protocols.

The US Food and Drug Administration (FDA) (FDA 2020) and European Medicines
Agency (EMA) (EMA 2009) recommend long-term follow-up for subjects treated with
gene therapy drug products in order to monitor for selected adverse events
(AEs) as well as durability of clinical response. Accordingly, Study LTF-304 is
being conducted as a long-term observational safety and efficacy follow-up
study for subjects who have received eli-cel in parent clinical studies.

This study has been transitioned to CTIS with ID 2024-513904-33-00 check the CTIS register for the current data.

• Monitor for long-term safety of the eli-cel administered in parent clinical
studies
• Monitor for long-term efficacy of eli-cel administered in parent clinical
studies

This is a multi-center, long-term safety and efficacy follow-up study for
subjects with cerebral adrenoleukodystrophy (CALD) who have received eli-cel in
parent clinical studies.

Eli-cel is defined as an autologous CD34+ cell-enriched population that
contains cells transduced with Lenti-D lentiviral vector encoding the human
adrenoleukodystrophy protein. In parent studies, male subjects with CALD are
infused on a single occasion with eli-cel, and then followed for 24 (±1) month
for safety and efficacy.

The US Food and Drug Administration (FDA) and European Medicines Agency (EMA)
recommend long-term follow-up for subjects treated with gene therapy drug
products to monitor for selected adverse events (AEs), as well as durability of
clinical response.
Therefore, after subjects have completed the parent clinical studies, they will
be asked to participate in a long-term follow-up Study LTF-304, in which they
will be followed every 4 months through their post-drug product infusion Year
10 Visit, and then every 6 months from the Year 10.5 Visit through their
post-drug product infusion Year 15 Visit.

Not applicable as no investigational medicinal product (IMP) will be
administered to the patients.

The majority of the burden and risks are those associated to the procedures
that participants will undertake.
Risks associated to the investigational procedures are the following: pain and
discomfort associated to blood sample and to potential bone marrow biopsies.
Risks associated to MRI are the following: adverse effects associated to the
contrast agents (gadolinium) and adverse effects to sedation or potential
general anaesthesia.
Additionally, there are specific potential risks associated with the gene
therapy. Those risks will be closely monitored during this long-term efficacy
and safety follow-up study.

This study is conducted in order to monitor the disease status of participants
and look for any possible long-term side effects. There may be no direct
benefit to participants from participating in this study. It is possible that
if any long-term side effects do occur, the monitoring patients receive while
on this study will ensure they receive proper treatment earlier than they might
have otherwise.
This study may help researchers understand more fully whether gene transfer to
treat CALD is safe and effective.