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| ID | Type | Description | Link |
|---|---|---|---|
| 2025-522039-33-00 | EU Trial (CTIS) Number |
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This study will examine what happens when patients with amyotrophic lateral sclerosis (ALS) are given an investigational medication (study drug) known as LTX-002. Specifically, the researchers will be looking at safety, tolerability (if someone has any side effects from the drug), pharmacokinetics (what the body does to the study drug) and pharmacodynamics (what the study drug does to the body). The study will also investigate the effect of the drug on indicators of the severity of ALS, such as markers in blood and in the cerebrospinal fluid (the fluid that surrounds the brain and spinal cord, CSF) and on measures of the participant's ability to move, speak, and breathe.
Eligible participants will be asked to visit the study site 9 times and stay overnight once. In addition, there will be telephone or video calls with the study staff on 8 separate occasions. Procedures will include:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LTX-002 | Experimental | LTX-002 is an antisense oligonucleotide (ASO) targeting SPTLC1 messenger RNA (mRNA). Several dose levels will be tested. |
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| Placebo (aCSF) | Placebo Comparator | Sterile aCSF solution formulation intended for intrathecal administration. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LTX-002 | Drug | LTX-002 is an antisense oligonucleotide (ASO) targeting SPTLC1 messenger RNA (mRNA). Several dose levels will be tested. |
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| Measure | Description | Time Frame |
|---|---|---|
| Safety and Tolerability (Adverse Events) | Incidence and severity of adverse events (AEs), treatment-emergent adverse events (TEAEs) and serious adverse events | Screening to Day 169 |
| Safety and Tolerability (Clinical Laboratory Tests) | Clinical laboratory tests including serum chemistry and hematology; urinalysis | Screening to Day 169 |
| Safety and Tolerability (Vital Signs) | Vital signs will be collected, including blood pressure (mm Hg), heart rate (beats per minute), respiratory rate (breaths per minute), body temperature (°C or °F), total body weight (kilograms), and height (centimeters). Body Mass Index (BMI) will be calculated using the values of total body weight and height, with the formula BMI = weight in kg/(height in cm)^2. | Screening to Day 169 |
| Safety and Tolerability (Physical and Neurological exams) | Physical and neurological exams will be performed periodically to ensure participant safety. Height (centimeters or inches), weight (kilograms or pounds) and body mass index (BMI; kilograms/meters^2) will be measured. | Screening to Day 169 |
| Safety and Tolerability (ECGs - heart rate) | Cardiovascular safety will be monitored by performing electrocardiogram (ECG) assessments, including heart rate | Screening to Day 169 |
| Safety and Tolerability (ECGs - QRS) | Cardiovascular safety will be monitored by performing electrocardiogram (ECG) assessments, including the QRS complex (normally 70-100 ms) |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics of LTX-002 (CSF and plasma levels) | The amount of LTX-002 in the cerebrospinal fluid (CSF) and plasma will be measured. | Day 1 to Day 169 |
| Pharmacokinetics of LTX-002 (Cmax) | The maximum observed plasma concentration (Cmax) of LTX-002 will be calculated. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of anti-LTX-002 antibodies in plasma | Number of participants with detectable anti-LTX-002 antibodies in plasma, as measured by a validated immunoassay. Antibody status and titers will be summarized descriptively by treatment group (LTX-002 or placebo). | Day 1 to Day 169 |
| Change from baseline in SPTLC1 protein concentration in cerebrospinal fluid |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trials Information | Contact | 267-503-4800 | clinical.trials@lealtx.com |
| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Leal Therapeutics, Inc | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Schleswig-Holstein, Campus Lübeck | Not yet recruiting | Lübeck | Germany |
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| ID | Term |
|---|---|
| D000690 | Amyotrophic Lateral Sclerosis |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
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Participants (8 per cohort, randomized in a 6:2 ratio to receive LTX-002 or placebo) will receive a total of three IT injections of LTX-002 (or placebo) on Days 1, 29, and 85
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| Placebo (aCSF) | Other | Sterile aCSF solution formulation intended for intrathecal administration. |
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| Time Frame: Screening to Day 169 |
| Safety and Tolerability (ECGs - QT) | Description: Cardiovascular safety will be monitored by performing electrocardiogram (ECG) assessments, including the QT interval measure | Screening to Day 169 |
| Safety and Tolerability (ECGs - QTc) | Cardiovascular safety will be monitored by performing electrocardiogram (ECG) assessments, including QTc (heart rate-corrected QT interval) | Screening to Day 169 |
| Safety and Tolerability (ECGs - PR intervals) | Cardiovascular safety will be monitored by performing electrocardiogram (ECG) assessments, including PR intervals (normally 120-200 ms) | Screening to Day 169 |
| Day 1 to Day 169 |
| Pharmacokinetics of LTX-002 (Tmax) | The time to maximum observed plasma concentration (Tmax) of LTX-002 will be calculated. | Day 1 through Day 169 |
| Pharmacokinetics of LTX-002 (AUC0-∞) | The area under the plasma-time concentration curve from time 0 extrapolated to infinity (AUC0-∞) of LTX-002 will be calculated. | Day 1 to Day 169 |
| Pharmacokinetics of LTX-002 (AUC0-t) | The area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC0-t) of LTX-002 will be calculated. | Day 1 to Day 169 |
| Pharmacokinetics of LTX-002 (Tlag) | The delay between the time of dosing and the time of appearance of the first measurable concentration (Tlag) of LTX-002 in plasma will be calculated. | Day 1 to Day 169 |
| Pharmacokinetics of LTX-002 (Vd/F) | The apparent volume of distribution (Vd/F) of LTX-002 in plasma, if applicable, will be calculated. | Day 1 to Day 169 |
| Pharmacokinetics of LTX-002 (λz) | The apparent terminal elimination rate constant (λz) of LTX-002 in plasma, if applicable, will be calculated. | Day 1 to Day 169 |
| Pharmacokinetics of LTX-002 (T1/2) | The half-life (T1/2) of LTX-002 in plasma, if applicable, will be calculated. | Day 1 to Day 169 |
| Pharmacokinetics of LTX-002 (CL/F) | The apparent clearance (CL/F) of LTX-002 in plasma, if applicable, will be calculated. | Day 1 to Day 169 |
Change from baseline in SPTLC1 protein concentration in cerebrospinal fluid compared with placebo. Levels will be measured using a validated assay and summarized as mean change from baseline by treatment group. |
| Day 1 to Day 169 |
| Change from baseline in ceramide and other sphingolipid concentrations in cerebrospinal fluid | Change from baseline in selected ceramide and sphingolipid concentrations in cerebrospinal fluid compared with placebo. Levels will be measured using a validated assay and summarized as mean change from baseline by treatment group. | Day 1 to Day 169 |
| Change from baseline in plasma neurofilament light chain (NfL) concentration | Change from baseline in plasma neurofilament light chain concentration compared with placebo. Levels will be measured using a validated assay and summarized as mean change from baseline by treatment group. | Day 1 to Day 169 |
| Change from baseline in monocyte chemoattractant protein-1 (MCP-1) concentration in cerebrospinal fluid | Change from baseline in monocyte chemoattractant protein-1 concentration in cerebrospinal fluid compared with placebo. Levels will be measured using a validated assay and summarized as mean change from baseline by treatment group | Day 1 to Day 169 |
| Change from baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) total score | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) provides a measure of how a person living with ALS is experiencing her or his disease, based on a set of 12 questions about symptoms and experiences of daily living. Each answer is given a numerical score between 0 (which indicates maximum problems or inability to perform a function) and 4 (which indicates normal functioning or no problems in this area). The total score of the ALSFRS-R thus ranges from 0 to 48, with lower scores indicating more difficulties and more severe symptoms of ALS. | Screening through Day 169 |
| Change from baseline in slow vital capacity (SVC) | Change from baseline in slow vital capacity compared with placebo. Results will be summarized as mean change from baseline by treatment group | Screening to Day 169 |
| Change from baseline in speech and bulbar function as assessed by speech analytics | Change from baseline in speech and bulbar function as assessed by speech analytics compared with placebo. Results will be summarized as change from baseline in derived speech metrics by treatment group | Screening to Day 169 |
| Change from baseline in muscle strength as measured by hand-held dynamometry | Change from baseline in muscle strength as measured by hand-held dynamometry compared with placebo. Results will be summarized as mean change from baseline by treatment grou | Screening to Day 169 |
| Istituto Neurologico "Carlo Besta" | Not yet recruiting | Milan | Italy |
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| AOU Città della Salute e della Scienza di Torino | Not yet recruiting | Torino | Italy |
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| Universitair Medisch Centrum Utrecht | Recruiting | Utrecht | Netherlands |
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| Karolinska Universitetssjukhuset | Recruiting | Stockholm | Sweden |
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| D019636 | Neurodegenerative Diseases |
| D057177 | TDP-43 Proteinopathies |
| D009468 | Neuromuscular Diseases |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |