LTX-002-101
Sponsored by Leal Therapeutics, Inc.
LTX-002-101 investigates the safety and tolerability of intrathecally administrated LTX-002 in participants with ALS.
This study investigates whether the investigational drug LTX-002 is safe and how well it is tolerated by people with ALS at different doses. Another objective of the study is to examine the effect of LTX-002 on biomarkers and symptoms of ALS. The drug is administered intrathecally (via a lumbar puncture, also known as a spinal tap).
The investigational compound: LTX-002
Sphingolipids are chemicals that cells use to build membranes and to send signals. Abnormally high levels of sphingolipids are linked to diseases including ALS. People with mutations in the SPTLC1 gene make too many sphingolipids and develop ALS, but even people with ALS who don’t have SPTLC1 mutations often have high levels of sphingolipids in their brains, spinal cords, and blood. LTX-002 is an antisense oligonucleotide (ASO) that binds to the messenger RNA for SPTLC1 and causes the body to produce less SPTLC1. The goal of reducing SPTLC1 is to lower the amount of sphingolipids in the body and to see if this is safe and if it could have any effects on ALS.
LTX-002 is administered via intrathecal administration (lumbar puncture, also known as a spinal tap).
Study design
This study is a Phase 1-2 study. The main goal of this study is to see whether the study drug is safe and well tolerated. The LTX-002-101 study is a double-blind, placebo-controlled study of seven cohorts, each consisting of eight participants. Each cohort will be given a different dose of LTX-002, beginning with a low dose and increasing with each successive cohort. In each cohort, six participants will receive the active compound and two will receive a placebo, thus the chance of getting the active compound is 75%. Each participant will be randomly assigned to receive LTX-002 or placebo, and the study doctors and participants will not know who receives which treatment until after the study has ended.
Each participant will receive 3 doses of study drug (LTX-002 or placebo) intrathecally, on day 1, day 29, and day 85. The duration of the study for each participant will be up to approximately 28 weeks, including a 4-week Screening Period, a 12-week Treatment Period, and a 12-week Follow-Up Period.
Administration of the study drug in each cohort will start with two participants: one will receive a single dose of LTX-002, and the other will receive a placebo. Participants will remain at the study site for observation for 24 hours after the first dose. After 72 hours, all the laboratory tests, vital signs, side effects and other clinical data from the first two participants will be reviewed. If there are no clinically concerning signals from these data, then the rest of the cohort (remaining six participants) will receive their dose, one by one. After 21 days, the data from each individual participant will be reviewed again before the next dose is administered to her or him (planned on day 29). After the second (day 29) and the third (day 85) doses, the participants will stay at the study site for observation for six hours.
After all eight participants in a cohort have received all three doses of study drug (LTX-002 or placebo), the safety and tolerability of the data from the whole cohort will be reviewed by the Data Safety Monitoring Board (DSMB). If the DSMB does not have any concerns, the first 2 participants in the next cohort will receive doses of study drug (one LTX-002 and one placebo). Because of this study design, the time between the start of two cohorts can be lengthy, however, this design is used to ensure the safety of all participants.
Can I participate in the study?
The main criteria to participate in this study are:
- Age between 18 to 75 years old
- Onset of first symptom leading to ALS diagnosis occurred ≤ 36 months prior to the screening visit.
- Lung function (Slow Vital Capacity) > 50%
- Body Mass Index (BMI) ≥18 and ≤40 kg/m2
- You’re able to participate in lengthy study visits, including one overnight stay at your ALS centre/hospital after the first dose.
- If you’re currently using ALS medication (riluzole, edaravone, or sodium phenylbutyrate + taurursodiol), a stable dose of this medication for at least 30 days prior to study participation is required.
Note: This list is not exhaustive, but these are the main criteria.
Registration and more information
If you are interested in participating in the LTX-002-101 study, please contact one of the participating TRICALS centres below (contact details can be found by clicking on ‘More about this centre’). Make use of the contact form on each Centre detail page, or when contacting the centre of your choice by email or telephone, please provide your full name, your date of birth and the date of onset of symptoms. The centre can provide you with more information about the study and/or inclusion criteria and answer any questions you may have. If you experience difficulty contacting a centre, you may reach out directly to the TRICALS operational team at info@tricals.org for support in this process.
