Skip to main content
OpenTrials
Recruiting

NCT Number: NCT07660614

A Study of LTX-002 in Adult Participants With Amyotrophic Lateral Sclerosis

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Amyotrophic Lateral Sclerosis Central Nervous System Diseases Metabolic Diseases Motor Neuron Disease Nervous System Diseases Neurodegenerative Diseases Neuromuscular Diseases Nutritional and Metabolic Diseases Proteostasis Deficiencies Spinal Cord Diseases TDP-43 Proteinopathies

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany

Loading trial locations.

About this study

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:

  • A review of medical history and medications
  • Physical exams, including a neurologic (nervous system) assessment
  • Electrocardiograms (a measure of the heart's electrical activity)
  • Blood, urine and cerebrospinal fluid (CSF) collection
  • Measures of lung function
  • Measures of speech
  • Measures of muscle strength
  • Scales to assess ALS symptoms and overall health, and feelings about suicide
  • Administration of the study drug (or placebo) by injection into the CSF through a lumbar (lower spinal area) injection

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diagnosis of ALS per Gold Coast criteria
  • ALS symptom onset less than 36 months prior to Screening
  • Slow vital capacity ≥ 50% of predicted value
  • Body mass index ≥18 and ≤40 kg/m2

Exclusion criteria

  • Current evidence or history of a clinically significant medical condition that, in the Investigator's judgement, would impact the participant's safety, interpretation of study results, or place the participant at high risk of poor treatment compliance or of not completing the study
  • History of brain or spinal abnormalities on magnetic imaging (MRI) or computed tomography (CT) that might interfere with the lumbar puncture (LP), cerebrospinal fluid (CSF) circulation or safety assessments
  • Prior treatment with antisense oligonucleotide (ASO), small interfering RNA, stem cell therapy, or gene therapy for any indication
  • Tracheostomy
  • HIV, Hepatitis B or C infection (acute or chronic)
  • Presence of implanted shunt (CSF) or vascular device
  • Risk for uncontrolled bleeding
  • Pregnant or breastfeeding

Treatment and study plan

LTX-002

Drug

LTX-002 is an antisense oligonucleotide (ASO) targeting SPTLC1 messenger RNA (mRNA). Several dose levels will be tested.

Placebo (aCSF)

Other

Sterile aCSF solution formulation intended for intrathecal administration.

Primary outcomes

  1. Safety and Tolerability (Adverse Events)

    Time frame: Screening to Day 169

    Incidence and severity of adverse events (AEs), treatment-emergent adverse events (TEAEs) and serious adverse events

  2. Safety and Tolerability (Clinical Laboratory Tests)

    Time frame: Screening to Day 169

    Clinical laboratory tests including serum chemistry and hematology; urinalysis

  3. Safety and Tolerability (Vital Signs)

    Time frame: Screening to Day 169

    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.

  4. Safety and Tolerability (Physical and Neurological exams)

    Time frame: Screening to Day 169

    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.

  5. Safety and Tolerability (ECGs - heart rate)

    Time frame: Screening to Day 169

    Cardiovascular safety will be monitored by performing electrocardiogram (ECG) assessments, including heart rate

  6. Safety and Tolerability (ECGs - QRS)

    Time frame: Time Frame: Screening to Day 169

    Cardiovascular safety will be monitored by performing electrocardiogram (ECG) assessments, including the QRS complex (normally 70-100 ms)

  7. Safety and Tolerability (ECGs - QT)

    Time frame: Screening to Day 169

    Description: Cardiovascular safety will be monitored by performing electrocardiogram (ECG) assessments, including the QT interval measure

  8. Safety and Tolerability (ECGs - QTc)

    Time frame: Screening to Day 169

    Cardiovascular safety will be monitored by performing electrocardiogram (ECG) assessments, including QTc (heart rate-corrected QT interval)

  9. Safety and Tolerability (ECGs - PR intervals)

    Time frame: Screening to Day 169

    Cardiovascular safety will be monitored by performing electrocardiogram (ECG) assessments, including PR intervals (normally 120-200 ms)

Secondary outcomes

  1. Pharmacokinetics of LTX-002 (CSF and plasma levels)

    Time frame: Day 1 to Day 169

    The amount of LTX-002 in the cerebrospinal fluid (CSF) and plasma will be measured.

  2. Pharmacokinetics of LTX-002 (Cmax)

    Time frame: Day 1 to Day 169

    The maximum observed plasma concentration (Cmax) of LTX-002 will be calculated.

  3. Pharmacokinetics of LTX-002 (Tmax)

    Time frame: Day 1 through Day 169

    The time to maximum observed plasma concentration (Tmax) of LTX-002 will be calculated.

  4. Pharmacokinetics of LTX-002 (AUC0-∞)

    Time frame: Day 1 to Day 169

    The area under the plasma-time concentration curve from time 0 extrapolated to infinity (AUC0-∞) of LTX-002 will be calculated.

  5. Pharmacokinetics of LTX-002 (AUC0-t)

    Time frame: Day 1 to Day 169

    The area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC0-t) of LTX-002 will be calculated.

  6. Pharmacokinetics of LTX-002 (Tlag)

    Time frame: Day 1 to Day 169

    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.

  7. Pharmacokinetics of LTX-002 (Vd/F)

    Time frame: Day 1 to Day 169

    The apparent volume of distribution (Vd/F) of LTX-002 in plasma, if applicable, will be calculated.

  8. Pharmacokinetics of LTX-002 (λz)

    Time frame: Day 1 to Day 169

    The apparent terminal elimination rate constant (λz) of LTX-002 in plasma, if applicable, will be calculated.

  9. Pharmacokinetics of LTX-002 (T1/2)

    Time frame: Day 1 to Day 169

    The half-life (T1/2) of LTX-002 in plasma, if applicable, will be calculated.

  10. Pharmacokinetics of LTX-002 (CL/F)

    Time frame: Day 1 to Day 169

    The apparent clearance (CL/F) of LTX-002 in plasma, if applicable, will be calculated.

Other outcomes

  1. Incidence of anti-LTX-002 antibodies in plasma

    Time frame: Day 1 to Day 169

    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).

  2. Change from baseline in SPTLC1 protein concentration in cerebrospinal fluid

    Time frame: 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.

  3. Change from baseline in ceramide and other sphingolipid concentrations in cerebrospinal fluid

    Time frame: Day 1 to Day 169

    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.

  4. Change from baseline in plasma neurofilament light chain (NfL) concentration

    Time frame: Day 1 to Day 169

    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.

  5. Change from baseline in monocyte chemoattractant protein-1 (MCP-1) concentration in cerebrospinal fluid

    Time frame: Day 1 to Day 169

    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

  6. Change from baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) total score

    Time frame: Screening through Day 169

    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.

  7. Change from baseline in slow vital capacity (SVC)

    Time frame: Screening to Day 169

    Change from baseline in slow vital capacity compared with placebo. Results will be summarized as mean change from baseline by treatment group

  8. Change from baseline in speech and bulbar function as assessed by speech analytics

    Time frame: Screening to Day 169

    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

  9. Change from baseline in muscle strength as measured by hand-held dynamometry

    Time frame: Screening to Day 169

    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

Study contacts

Contact information is provided by the study sponsor or research team.

Clinical Trials Information

CONTACT

[email protected]

267-503-4800

Sponsors and collaborators

Lead sponsor

Leal Therapeutics, Inc

Industry

Registry information

Official study title

A First-in-Human, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study of Intrathecally Administered LTX-002 in Adult Participants With Amyotrophic Lateral Sclerosis

Acronym: NeurALS

Important dates

Study start
2026
Primary completion
2031
Study completion
2031
First posted
Jun 22, 2026
Registry last updated
Jun 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.