Amyotrophic Lateral Sclerosis
Conditions
Keywords
ALS
Brief summary
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.
Detailed description
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
Interventions
DRUGLTX-002
LTX-002 is an antisense oligonucleotide (ASO) targeting SPTLC1 messenger RNA (mRNA). Several dose levels will be tested.
OTHERPlacebo (aCSF)
Sterile aCSF solution formulation intended for intrathecal administration.
Sponsors
Leal Therapeutics, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
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
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability (Adverse Events) | Screening to Day 169 | Incidence and severity of adverse events (AEs), treatment-emergent adverse events (TEAEs) and serious adverse events |
| Safety and Tolerability (Clinical Laboratory Tests) | Screening to Day 169 | Clinical laboratory tests including serum chemistry and hematology; urinalysis |
| Safety and Tolerability (Vital Signs) | 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. |
| Safety and Tolerability (Physical and Neurological exams) | 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. |
| Safety and Tolerability (ECGs - heart rate) | Screening to Day 169 | Cardiovascular safety will be monitored by performing electrocardiogram (ECG) assessments, including heart rate |
| Safety and Tolerability (ECGs - QRS) | Time Frame: Screening to Day 169 | Cardiovascular safety will be monitored by performing electrocardiogram (ECG) assessments, including the QRS complex (normally 70-100 ms) |
| Safety and Tolerability (ECGs - QT) | Screening to Day 169 | Description: Cardiovascular safety will be monitored by performing electrocardiogram (ECG) assessments, including the QT interval measure |
| Safety and Tolerability (ECGs - QTc) | Screening to Day 169 | Cardiovascular safety will be monitored by performing electrocardiogram (ECG) assessments, including QTc (heart rate-corrected QT interval) |
| Safety and Tolerability (ECGs - PR intervals) | Screening to Day 169 | Cardiovascular safety will be monitored by performing electrocardiogram (ECG) assessments, including PR intervals (normally 120-200 ms) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of LTX-002 (CSF and plasma levels) | Day 1 to Day 169 | The amount of LTX-002 in the cerebrospinal fluid (CSF) and plasma will be measured. |
| Pharmacokinetics of LTX-002 (Cmax) | Day 1 to Day 169 | The maximum observed plasma concentration (Cmax) of LTX-002 will be calculated. |
| Pharmacokinetics of LTX-002 (Tmax) | Day 1 through Day 169 | The time to maximum observed plasma concentration (Tmax) of LTX-002 will be calculated. |
| Pharmacokinetics of LTX-002 (AUC0-∞) | 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. |
| Pharmacokinetics of LTX-002 (AUC0-t) | 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. |
| Pharmacokinetics of LTX-002 (Tlag) | 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. |
| Pharmacokinetics of LTX-002 (Vd/F) | Day 1 to Day 169 | The apparent volume of distribution (Vd/F) of LTX-002 in plasma, if applicable, will be calculated. |
| Pharmacokinetics of LTX-002 (λz) | Day 1 to Day 169 | The apparent terminal elimination rate constant (λz) of LTX-002 in plasma, if applicable, will be calculated. |
| Pharmacokinetics of LTX-002 (T1/2) | Day 1 to Day 169 | The half-life (T1/2) of LTX-002 in plasma, if applicable, will be calculated. |
| Pharmacokinetics of LTX-002 (CL/F) | Day 1 to Day 169 | The apparent clearance (CL/F) of LTX-002 in plasma, if applicable, will be calculated. |
Countries
Germany, Italy, Netherlands, Sweden
Contacts
CONTACTClinical Trials Information
STUDY_DIRECTORMedical Monitor
Leal Therapeutics, Inc
Outcome results
None listed