A Study of LTX-002 in Adult Participants With Amyotrophic Lateral Sclerosis
ConditionAmyotrophic Lateral Sclerosis
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorLeal Therapeutics, Inc
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
LTX-002
DrugLTX-002 is an antisense oligonucleotide (ASO) targeting SPTLC1 messenger RNA (mRNA). Several dose levels will be tested.
Placebo (aCSF)
Other interventionSterile aCSF solution formulation intended for intrathecal administration.
Treatment groups
56 Participants
are divided into 2 treatment groupsGroup A: LTX-002Experimental treatment 1 intervention
Group B: Placebo (aCSF)Placebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Safety and Tolerability (Adverse Events)
Incidence and severity of adverse events (AEs), treatment-emergent adverse events (TEAEs) and serious adverse events
Time frame
Screening to Day 1692
Safety and Tolerability (Clinical Laboratory Tests)
Clinical laboratory tests including serum chemistry and hematology; urinalysis
Time frame
Screening to Day 1693
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.
Time frame
Screening to Day 1694
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.
Time frame
Screening to Day 169Secondary outcomes
1
Pharmacokinetics of LTX-002 (CSF and plasma levels)
The amount of LTX-002 in the cerebrospinal fluid (CSF) and plasma will be measured.
Time frame
Day 1 to Day 1692
Pharmacokinetics of LTX-002 (Cmax)
The maximum observed plasma concentration (Cmax) of LTX-002 will be calculated.
Time frame
Day 1 to Day 1693
Pharmacokinetics of LTX-002 (Tmax)
The time to maximum observed plasma concentration (Tmax) of LTX-002 will be calculated.
Time frame
Day 1 through Day 1694
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.
Time frame
Day 1 to Day 169Other outcomes
1
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).
Time frame
Day 1 to Day 1692
Change from baseline in SPTLC1 protein concentration in cerebrospinal fluid
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.
Time frame
Day 1 to Day 1693
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.
Time frame
Day 1 to Day 1694
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.
Time frame
Day 1 to Day 169Sponsors and contacts
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Source ClinicalTrials.gov