Safety and Preliminary Efficacy of Aleeto in Amyotrophic Lateral Sclerosis

NCT06181526 | Unknown Phase 1 DMC

• 1 other identifier: KY2023-252-01
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center, randomized, double-blind, placebo parallel-controlled, dose-escalation clinical study. The aim of this study was to evaluate the safety, tolerability, and preliminary effect of Aleeto in adult patients with ALS, and to provide an appropriate dose for the future clinical trial.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Placebo parallel-controlled; Single-center Study; Double Blind Study; Randomized Controlled Trial; Dose escalation clinical study; Aleeto

Outcome Measures

Primary Outcomes (2)

• Adverse events and serious adverse events (SAEs)

  Close monitoring of patients for any physical discomfort, such as shortness of breath, rash, etc. Regular follow-up examinations of liver function, kidney function, blood routine, and other laboratory parameters should be performed. Adverse events includes abnormal liver biochemical indicators, hypersensitivity, liver failure, dyspnea, etc.

  from Day 1 to Day 120

• Incidence of changes in clinical laboratory examination indicators, changes in vital signs, abnormal neurological examination and abnormal electrocardiogram

  After Aleeto treatment in adult patients with ALS, monitor patients' blood routine, biochemistry, vital signs, electrocardiogram, physical examination, and other parameters.

  from Day 1 to Day 120

Secondary Outcomes (6)

• Immunological markers

  Day 2, Day 7, Day 14, Day 30, Day 32, Day 37, Day 60, Day 62, Day 67, Day 90, Day 120

• Time to invasive mechanical ventilation and death

  Day 2, Day 7, Day 14, Day 30, Day 32, Day 37, Day 60, Day 62, Day 67, Day 90, Day 120

• Pharmacokinetics analysis

  Day 1, Day 6, Day 13, Day 31, Day 36, Day 61, Day 66

• Pharmacokinetics analysis

  Day 1, Day 6, Day 13, Day 31, Day 36, Day 61, Day 66

• Pharmacokinetics analysis

  Day 1, Day 6, Day 13, Day 31, Day 36, Day 61, Day 66

Study Arms (4)

Intrathecal administration combined with intravenous administration of Aleeto(0.5μg/kg) or placebo

EXPERIMENTAL

Four patients will be randomly assigned to the treatment group and the placebo group. 3 patients will receive intrathecal administration combined with intravenous administration of 0.5 μg/kg Aleeto and sodium chloride, while another patient will receive the same dose of placebo. Day 1-12: Intrathecal administration of Aleeto will be conducted on Days 1, 4, 8, and 11, and intravenous administration of Aleeto on Days 2, 3, 5, 6, 9, 10, 12, and 13. Day 31-36: Intrathecal administration of Aleeto will be conducted on Days 31 and 34, and intravenous administration of Aleeto on Days 32, 33, 35, and 36. D61-66: Intrathecal administration of Aleeto will be conducted on Days 61 and 64, and intravenous administration of Aleeto on Days 62, 63, 65, and 66.

Drug: Aleeto; Device: intravenous injection; Device: intrathecal injection

Intrathecal administration combined with intravenous administration of Aleeto (1μg/kg) or placebo

EXPERIMENTAL

Seven patients will be randomly assigned to the treatment group and the placebo group. 6 patients will receive intrathecal administration combined with intravenous administration of 1μg/kg Aleeto and sodium chloride, while another patient will receive the same dose of placebo. Day1-12: Intrathecal injection of Aleeto would be given on Day 1, 4, 8, and 11, and intravenous injection of Aleeto on Day 2, 3, 5, 6, 9, 10, 12, and 13. Day31-36: Intrathecal injection of Aleeto would be given on Day 31 and 34, and intravenous injection of Aleeto on Day 32, 33, 35, and 36. D61-66: Intrathecal injection of Aleeto would be given on Day 61 and 64, and intravenous injection of Aleeto on Day 62, 63, 65, and 66.

Drug: Aleeto; Device: intravenous injection; Device: intrathecal injection

intrathecal injection and intravenous injection of Aleeto (2μg/kg) or placebo

EXPERIMENTAL

Seven patients will be randomly assigned to the treatment group and the placebo group. 6 patients will receive intrathecal administration combined with intravenous administration of 2μg/kg Aleeto and sodium chloride, while another patient will receive the same dose of placebo. Day1-12: Intrathecal injection of Aleeto would be given on Day 1, 4, 8, and 11, and intravenous injection of Aleeto on Day 2, 3, 5, 6, 9, 10, 12, and 13. Day31-36: Intrathecal injection of Aleeto would be given on Day 31 and 34, and intravenous injection of Aleeto on Day 32, 33, 35, and 36. D61-66: Intrathecal injection of Aleeto would be given on Day 61 and 64, and intravenous injection of Aleeto on Day 62, 63, 65, and 66.

Drug: Aleeto; Device: intravenous injection; Device: intrathecal injection

intravenous injection of Aleeto (2μg/kg)

EXPERIMENTAL

Six patients will receive intravenous administration of 2 μg/kg Aleeto and sodium chloride. Day1-12: Patients would be given intravenous injection of Aleeto(2μg/kg) +100ml sodium chloride for 12 days (Day 1 to 6, 8 to 13) once a day. Day31-36: Patients would be given intravenous injection of Aleeto(2μg/kg) +100ml sodium chloride for 6 days (Day 31 to 36) once a day. D61-66: Patients would be given intravenous injection of Aleeto(2μg/kg) +100ml sodium chloride for 6 days (Day 61 to 66) once a day.

Drug: Aleeto; Device: intravenous injection

Interventions

Aleeto DRUG

According to the groups, patients would be treated with Aleeto via intrathecal injection or intravenous injection, and the specific dosage and administration method of Aleeto will depend on the grouping.

Intrathecal administration combined with intravenous administration of Aleeto (1μg/kg) or placebo; Intrathecal administration combined with intravenous administration of Aleeto(0.5μg/kg) or placebo; intrathecal injection and intravenous injection of Aleeto (2μg/kg) or placebo; intravenous injection of Aleeto (2μg/kg)

intravenous injection DEVICE

According to the groups, patients would be treated with Aleeto or placebo +100ml sodium chloride injection via intravenous injection, depend on the grouping

Intrathecal administration combined with intravenous administration of Aleeto (1μg/kg) or placebo; Intrathecal administration combined with intravenous administration of Aleeto(0.5μg/kg) or placebo; intrathecal injection and intravenous injection of Aleeto (2μg/kg) or placebo; intravenous injection of Aleeto (2μg/kg)

intrathecal injection DEVICE

According to the groups, patients would be treated with Aleeto or placebo + 8ml sodium chloride injection via intrathecal injection, depend on the grouping.

Intrathecal administration combined with intravenous administration of Aleeto (1μg/kg) or placebo; Intrathecal administration combined with intravenous administration of Aleeto(0.5μg/kg) or placebo; intrathecal injection and intravenous injection of Aleeto (2μg/kg) or placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who are qualified for the clinical trial program cycle judged by well-trained physicians;
• years old≤ age≤ 75 years old, males or females;
• Forced vital capacity ≥ 80% of predicted vital capacity during the screening period;
• The total score of the ALSFRS-R scale ≥ 30 points and ≤40 points during enrollment, and the respiratory function item ≥ 3 points;
• Diagnosis of confirmed or probable ALS in accordance with the revised EI Escorial diagnostic criteria for amyotrophic lateral sclerosis of the World Federation of Neurology;
• Subjects or their legal representatives clearly understand and voluntarily participate in the study and sign the informed consent form;
• Subjects (including male subjects) are willing to have no birth plan and voluntarily take effective contraceptive measures during the entire study period and within 3 months after the end of the study, and have no plan to donate sperm or eggs.

You may not qualify if:

• Diagnosed with familial ALS (based on family history);
• With obvious cognitive impairment (MMSE scale: ≤19 points in the illiteracy group，≤ 22 points in the primary school group, and ≤26 points in the junior high school group (more than 8 years of education);
• Obvious dysphagia;
• Positive HIV test or history of positive test;
• Positive hepatitis C virus antibody or positive test history;
• Hepatitis B active infection (hepatitis B surface antigen positive and/or serum HBV DNA positive or serum HBV DNA \> 2 × 108 IU/ml;
• Have used other investigational drugs within 1 month or within 5 drug half-lives;
• Diseases and deformities of the lumbar spine;
• Have other conditions known to be associated with motor neuron dysfunction that may confuse or obscure an ALS diagnosis;
• Other psychiatric disorders diagnosed according to DSM-V diagnostic criteria, or significant suicide intent;
• With severe hepatic insufficiency, renal insufficiency or severe cardiac insufficiency (severe hepatic insufficiency refers to ALT value≥2.0 times the upper limit of normal value or AST value≥2.0 times the upper limit of normal value; severe renal insufficiency refers to CRE≥1.5 times the upper limit of normal value or eGFR\<40mL/min/1.73m2; severe cardiac insufficiency refers to NYHA class 3-4);
• Permanently dependent on ventilator-assisted ventilation;
• History of alcohol and drug abuse; Edaravone users;
• Patients who are pregnant, breast-feeding, or who are likely to become pregnant and plan to become pregnant;
• Patients participating in other clinical trials or using other biological agents, drugs, or devices under investigation;

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital

Beijing, 100050, China

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Injections, Intravenous; Injections, Spinal

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Administration, Intravenous; Drug Administration Routes; Drug Therapy; Therapeutics; Injections

Study Officials

• Yilong Wang, MD+PhD

  Capital Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yilong Wang, MD+PhD

CONTACT

13911666571; yilong528@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President of Beijing Tiantan Hospital

Model Details: In this study, a dose-escalation clinical trial is conducted to explore the maximum tolerated dose, and three dose groups are set: 0.5 μg/kg, 1 μg/kg, and 2 μg/kg, with 3 cases in the initial dose group and placebo group, and 6 cases in the follow-up dose group, with a total of 24 subjects.

Study Record Dates

• First Submitted: December 6, 2023
• First Posted: December 26, 2023
• Study Start: December 15, 2023
• Primary Completion: October 30, 2024
• Study Completion: October 30, 2024
• Last Updated: December 26, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)