Evaluate the Safety of Neuronata-R® Inj. Suspended With HypoTHermosol® FRS (HTS-FRS) in Patients With ALS

NCT06676423 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: NEURONATA-ALSHT122
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is a single-center, open-label, and phase I clinical trial to Evaluate the Safety of Neuronata-R® Inj. suspended with HypoTHermosol® FRS (HTS-FRS) in Patients with Amyotrophic Lateral Sclerosis.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic Lateral Sclerosis; Mesenchymal stem cell; cell theraphy; ALS; HypoThermosol(HTS-FRS); Phase 1 clinical trial

Outcome Measures

Primary Outcomes (4)

• tolerability Assessment

  HTS-FRS DLT expression for each dose step

  through study period, an average of 8week

• Safety Assessment

  Adverse Events(including DLT)

  through study period, an average of 8week

• Safety Assessment

  Clinical Laboratory Analysis(Change in laboratory test results at the time of visit after IP administration compared to baseline)

  Baseline and 26day, 8week

• Safety Assessment

  Cerebrospinal Fluid Analysis(Changes in cerebrospinal fluid results at 26day compared to 0day)

  0 Day, 26 Day

Secondary Outcomes (2)

• Exploratory Assessment

  baseline and 26day , 8week

• Exploratory Assessment

  within -8week and 0day, 8week

Study Arms (1)

Groups/Cohorts

EXPERIMENTAL

In the first-stage dose, a 1:1 mixture of autologous CSF and HypoThermosol® FRS (HTS-FRS) is used as a suspension, and in the second-stage dose, only HypoThermosol® FRS (HTS-FRS) is used as a suspension without cerebrospinal fluid. Mix 1.0 ⅹ 10\^6 cells per kg of body weight with the suspension at the dose level below 1. First stage dose: HTS-FRS 0.5mL/10kg + cerebrospinal fluid 0.5mL/10kg 2. Second stage dose: HTS-FRS 1.0mL/10kg

Biological: Lenzumestrocel; Drug: Riluzole

Interventions

Lenzumestrocel BIOLOGICAL

1.0 ⅹ 10\^6 cells/kg of Neuronata-R mixed with HTS-FRS suspension are administered twice in the cerebrospinal fluid at intervals of 26 days

Also known as: Neuronata-R, Autologous Bone Marrow derived Mesenchymal Stem cell

Groups/Cohorts

Riluzole DRUG

In the case of a subject who is not taking Riluzole at the time of screening (visit 1), Riluzole should be taken except when discontinued due to Adverse events. The dose can be changed within the authorization according to the medical expert's judgement

Also known as: Rilutek

Groups/Cohorts

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Among subjects diagnosed with familial or sporadic amyotrophic lateral sclerosis
• Subjects whose ALSFRS-R scores are in the range of 25\~46 at the time of screening (Visit 1).
• Subjects who are able to visit the site by themselves or with other's support.
• When subjects and/or their legal guardians consent to participating in this clinical study.
• Subjects deemed, by the investigator, capable of complying with the clinical study protocol
• For child-bearing aged female subjects: Subjects who consent to sexual abstinence (refraining from sexual intercourse) or use of contraception method with annual failure rate of \< 1% during the study period.
• A female subject who has experienced the menarche, does not reach the menopause (or 12-month or longer amenorrhea for unknown reasons except menopause) and does not receive surgical sterilization (ovariectomy and/or hysterectomy) is regarded as the child-bearing aged woman.
• Examples of contraception methods with annual failure rate of \< 1% include bilateral tubal ligation, vasectomy, appropriate use of hormonal contraceptives that inhibit ovulation (supplemented by barrier method and spermicide), hormone-releasing intrauterine device and copper intrauterine device.
• Based on clinical study period and subject's preferred lifestyle, the reliability of sexual abstinence should be evaluated. Periodic abstinence (e.g., calendar method, ovulation and post-ovulation symptothermal method) and extravaginal ejaculation are not acceptable contraception methods.
• For male subjects: Subjects who, as described below, consent to sexual abstinence (refraining from sexual intercourse) or use of contraception method and consent to refrain from donation of sperm.
• When a male subject has his child-bearing aged female partner or pregnant female partner, he should maintain sexual abstinence or use condom to avoid exposure to embryo. Such male subject should not donate sperm during this period.
• Based on clinical study period and subject's preferred lifestyle, the reliability of sexual abstinence should be evaluated. Periodic abstinence and extravaginal ejaculation are not acceptable contraception methods.

You may not qualify if:

• Subjects who fail to satisfy ALS diagnosis criteria according to the revised World Federation of Neurology El Escorial Criteria \[Rix Brooks, 2000\].
• Subjects expected to have side effects on administration of cell therapy (such as subjects suspected to have malignant tumor, high-risk subjects vulnerable to psychogenic shock and severe hypertension subjects).
• ALSFRS-R score of less than 25 and 47 or higher during screening (visit 1)
• Subjects who fall into above Class II according to the New York Heart Association's functional classification (see the attachment), who have showed myocardial infarction, unstable arrhythmia and/or other significant cardiovascular diseases such as unstable angina in the past 3 months, or who show electrocardiographic signs of myocardial infarction or angina at the time of screening (Visit 1) or who received stent insertion or coronary artery bypass grafting.
• Subjects who have experienced epileptic seizure.
• Subjects with severe renal disorder (serum creatinine: not less than 3.0 mg/dL).
• Subjects with severe hepatic disorder (ALT, AST, or bilirubin: over 2.0 times of the normal upper limit).
• Subjects who show hemorrhagic tendency at the time of screening (PT and aPTT \> 1.5 x ULN)
• Subjects who are found to have active viral infections (such as HBsAg, HCV Ab, HIV Ab, CMV IgM, EBV IgM, HSV IgM and Treponema pallidum) at the time of screening.
• Subjects with hypersensitivity to antibiotics (penicillin or streptomycin).
• Subjects with any malignant tumor in the past 5 years before screening, except malignant tumors with very low risk of metastasis or death (such as appropriately treated cervical intraepithelial neoplasia, skin basal or squamous cell carcinoma, localized prostate cancer or ductal carcinoma in situ).
• Subjects who are receiving any medicinal products that may affect bone marrow functions.
• Subjects with severe mental disorders (such as schizophrenia and bipolar disorder. However, exception applies to mild ALS-related cognitive impairment and secondary emotional trauma).
• Subjects for whom administration of investigational product is prohibited, subjects with conditions that may affect interpretation of results or subjects with conditions that may result in high risk of complications, such as the rest diseases, metabolic disorders, physical examination results and/or laboratory test results as diseases or such conditions are reasonably suspected.

Sponsors & Collaborators

• Corestemchemon, Inc.: lead

Study Sites (1)

Hanyang university hospital

Seoul, 04763, South Korea

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Riluzole

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)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Seung Hyun Kim, MD, PhD

  Hanyang University Seoul Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2024
• First Posted: November 6, 2024
• Study Start: November 9, 2022
• Primary Completion: November 27, 2023
• Study Completion: November 27, 2023
• Last Updated: November 6, 2024

Record last verified: 2024-11

Locations

KR (1)