A Study to Investigate the Safety and Effects of LTX-002 Administered in the Spinal Canal of Participants with Amyotrophic Lateral Sclerosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Leal Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

9 Apr 2026 → ongoing

Decision date (initial)

2026-01-23

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Leal Therapeutics Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Pharmacokinetic, Pharmacodynamic, Safety

To evaluate the safety and tolerability of intrathecally (IT) administered LTX-002 in adult participants with amyotrophic lateral sclerosis (ALS) compared to placebo.

Secondary objectives 1

1. To evaluate the pharmacokinetics (PK) of LTX-002 after IT administration in adult participants with ALS

Conditions and MedDRA coding

Amyotrophic Lateral Sclerosis

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. The participant is a male or female, 18 to 75 years of age, inclusive, at the time of consent.
2. The participant has a diagnosis of ALS per Gold Coast criteria.
3. The participant had ALS symptom onset less than 36 months prior to Screening.
4. The participant is capable of providing informed consent. Both of the following criteria must be met: a. The participant must be fluent (oral and written) in the local language to consent. b. An informed consent form (ICF) must be signed by the participant before any study assessments are performed. c. If the participant is able to comprehend and is willing to sign the ICF, but cannot physically sign the ICF, an impartial witness must sign the ICF.
5. An SVC ≥ 50% of predicted value as adjusted for sex, age, and height (from the sitting position).
6. If taking riluzole, edaravone, or sodium phenylbutyrate + taurursodiol, participants must be on a stable dose for ≥ 30 days prior to Day 1 and be expected to remain at that dose until the final study visit (Day 169).
7. Medically able to undergo the study procedures and to adhere to the visit schedule at the time of study entry, as determined by the PI.
8. Screening values of coagulation parameters including platelet count, International Normalization Ratio, prothrombin time, and activated partial thromboplastin time should be within normal ranges.
9. Body mass index ≥18 and ≤40 kg/m2
10. Female participants of childbearing potential with male partners, and male participants with female partners of child-bearing potential must be willing to use two effective methods of contraception (with at least one being highly effective) from Day 1 until 3 months after their last dose of study drug.

Exclusion criteria 22

1. Current evidence or history of a clinically significant medical condition, including clinically meaningful frailty as determined by the Investigator, or an abnormal laboratory value 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. This includes significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, and neurologic disease.
2. History of cancer, with the exception of adequately treated basal cell or squamous cell carcinoma of the skin and cervical cancer.
3. History of brain or spinal abnormalities on magnetic imaging (MRI) or computed tomography that might interfere with the LP, CSF circulation or safety assessments, such as subarachnoid hemorrhage, suggestion of raised intracranial pressure on MRI or ophthalmic examination, spinal stenosis or curvature, spina bifida occulta, a Chiari malformation, hydrocephalus, syringomyelia, tethered spinal cord syndrome, frontotemporal brain sagging syndrome and connective tissue disorders such as Ehlers Danlos and Marfan Syndromes.
4. 12-lead electrocardiogram (ECG) demonstrating left bundle branch block or corrected QT interval by Fridericia’s formula (QTcF) >450 milliseconds for men and >460 milliseconds for women. In participants with right bundle branch block, a QT interval of up to 480 milliseconds may be allowed after consultation with the medical monitor. If QTcF exceeds 450 milliseconds for men and >460 milliseconds for women, the ECG should be repeated 2 more times and the average of the 3 QTcF values should be used to determine the participant’s eligibility.
5. ANY of the following abnormalities in clinical laboratory tests at Screening, as assessed by the study-specific laboratory and confirmed by a single repeat, if deemed necessary: a. Serum creatinine level more than 1.5-fold above the upper limit of normal (ULN) or an estimated glomerular filtration rate value <60 mL/min/1.73 m2 calculated with the “2021 Chronic Kidney Disease Epidemiology Collaboration formula for Estimated Glomerular Filtration Rate” or urine albumin to creatinine ratio of >300 mg/g at Screening. b. Alanine transaminase, aspartate aminotransferase or bilirubin ≥1.5 × ULN or history of portal hypertension. Participants with known Gilbert Syndrome and elevated bilirubin may participate.
6. Treatment with another investigational drug (including investigational drugs for ALS through compassionate use programs), biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer, before Screening
7. Prior treatment with ASO, small interfering ribonucleic acid (RNA), stem cell therapy, or gene therapy for any indication.
8. Current or anticipated need, in the opinion of the Investigator, of a diaphragmatic pacing system during the study period.
9. Tracheostomy.
10. Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter.
11. Presence of any implanted vascular devices, including but not limited to pacemakers, vascular stents and prosthetic heart valves.
12. Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is not managed optimally and could place a participant at an increased risk for intraoperative or postoperative bleeding. These could include, but are not limited to, anatomical factors at or near the LP site (e.g., vascular abnormalities, neoplasms, or other abnormalities) and underlying disorders of the coagulation cascade, platelet function, or platelet count (e.g., hemophilia, Von Willebrand’s disease, liver disease).
13. Anticipated need, in the opinion of the Investigator, for administration of any antiplatelet or anticoagulant medication (e.g., clopidogrel, apixaban) for 7 days before or 48 hours after an LP. Low-dose (≤81mg daily) aspirin for cardiovascular prophylaxis is allowed.
14. Confirmed coronavirus disease 2019 (COVID-19) or positive influenza test within 4 weeks prior to Day 1. Regional and site COVID-19 testing policies should be followed throughout the study.
15. History of a positive test result for human immunodeficiency virus (HIV) or is positive at Screening.
16. Acute or chronic hepatitis C infection (defined as positive hepatitis C virus [HCV] antibody and detectable HCV RNA).
17. Acute or chronic hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg]). Participants with immunity to hepatitis B from previous natural infection or vaccination (defined as negative HBsAg, positive hepatitis B surface antibody, ± anti-hepatitis B core antigen [HbcAg]) are eligible to participate in the study.
18. Diagnosis of moderate to severe substance use disorder per DSM-5 criteria (except tobacco use disorder) within the 12 months before Screening (confirmed at Screening), or current abuse as determined by urine toxicology screen. Cannabis is allowed if a) it is legal in the region where the participant resides AND b) it would not, in the investigator’s judgment, interfere with the participant’s ability to comply with the requirements in the protocol.
19. At risk for suicidal behavior during the study as determined by the investigator’s clinical assessment and Columbia Suicide Severity Rating Scale (C-SSRS) as confirmed by the following: a. Answers “Yes” on items 4 or 5 (C-SSRS – ideation) with the most recent episode occurring within the 2 months before Screening, OR b. Answers “Yes” to any of the 5 items (C-SSRS-behavior) with an episode occurring within the 12 months before Screening. Non-suicidal self-injurious behavior is not exclusionary.
20. Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
21. Donated blood or blood products >450 mL within 30 days before study drug administration.
22. History of relevant drug allergies (i.e., allergy to any study drug or excipients, to a broad range of anesthetics)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Incidence and severity of AEs, TEAEs and SAEs
2. Clinical laboratory tests (serum chemistry and hematology; urinalysis)
3. ECGs
4. Vital signs (blood pressure, heart rate, respiratory rate, body temperature)
5. Physical and neurological exams.

Secondary endpoints 3

1. CSF levels of LTX-002
2. Single-dose plasma PK parameters for the first and last of the three doses, including Cmax, Tmax, AUC0-t, AUC0-∞, Tlag if applicable, Vd/F, λz, T1/2, and CL/F
3. Where data are available, AUC0-∞ AUC0 t, and Cmax will be tested for dose proportionality using a power model approach.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Leal Therapeutics Inc.

Sponsor organisation

Leal Therapeutics Inc.

Address

17 Briden Street Office 329

City

Worcester

Postcode

01605-2662

Country

United States

Scientific contact point

Organisation

Leal Therapeutics Inc.

Contact name

Lawrence Severt

Public contact point

Organisation

Leal Therapeutics Inc.

Contact name

Lawrence Severt

Third parties 7

Locations

4 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 75 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications