Evaluation the Efficacy and Safety of Mutiple Lenzumestrocel (Neuronata-R® Inj.) Treatment in Patients with ALS

NCT ID: NCT04745299

Last Updated: 2025-01-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-23
• Study Completion Date: 2026-05-03

Brief Summary

ALSUMMIT is a double-blind, randomized, placebo-controlled, multi-center, parallel, phase III clinical trial to evaluate and confirm the efficacy and long-term safety of repeated Lenzumestrocel (Neuronata-R® inj.) treatment.

Detailed Description

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by selective and progressive loss of motor neurons. Disease progression leads to death within 2-4 years, but there exists no definite treatment so far.

Based on phase I/II clinical trial(NCT01363401), twice intrathecal autologous bone marrow-derived mesenchymal stem cells (Lenzumestrocel) injections showed significant therapeutic benefit lasting at least six months with safety in patients with ALS.

Additionally, the switch from pro- to anti-inflammatory conditions, which was indicated from the inverse correlation between TGF-β1 and MCP-1 levels after Lenzumestrocel injections in the good responder, has been considered a plausible beneficial action mechanism.

This study is designed to investigate the following. First, to reconfirm and evaluate the long-term efficacy of twice injections (single cycle) of Lenzumestrocel, group 1 will receive a single cycle injection with a 26-day interval.

Second, to evaluate the long-term safety and efficacy of Lenzumestrocel repeated injections, group 2 will receive a single cycle injection a 26-day apart followed by three times injections every three-month interval.

Group 3 will receive comparator injections.

Conditions

Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Single cycle administration group

Study drug injections twice in a 26-day interval followed by three times comparator injections every three months.

Group Type: EXPERIMENTAL

Lenzumestrocel

Intervention Type: BIOLOGICAL

Single cycle administration group : injections twice in a 26-day interval Multiple administration group : injections twice in a 26-day interval followed by repeated three times injections every three months

Riluzole

Intervention Type: DRUG

concomitant administration of Riluzole to all groups, except subjects to whom Riluzole administration is deemed impossible owing to adverse events as determined by medical experts

Placebo Comparator

Intervention Type: DRUG

Single cycle administration group: Placebo comparator is injected three times every three months after injection of Lenzumestrocel twice in a 26-day interval.

Control group: Placebo comparator is injected twice in a 26-day interval followed by repeated three times injcections every three months

Multiple administation group

Study drug injections twice in a 26-day interval followed by repeated three times study drug injections every three months.

Group Type: EXPERIMENTAL

Lenzumestrocel

Intervention Type: BIOLOGICAL

Single cycle administration group : injections twice in a 26-day interval Multiple administration group : injections twice in a 26-day interval followed by repeated three times injections every three months

Riluzole

Intervention Type: DRUG

concomitant administration of Riluzole to all groups, except subjects to whom Riluzole administration is deemed impossible owing to adverse events as determined by medical experts

Control group

Comparator injections twice in a 26-day interval followed by three times comparator injections every three months.

Group Type: PLACEBO_COMPARATOR

Riluzole

Intervention Type: DRUG

concomitant administration of Riluzole to all groups, except subjects to whom Riluzole administration is deemed impossible owing to adverse events as determined by medical experts

Placebo Comparator

Intervention Type: DRUG

Single cycle administration group: Placebo comparator is injected three times every three months after injection of Lenzumestrocel twice in a 26-day interval.

Control group: Placebo comparator is injected twice in a 26-day interval followed by repeated three times injcections every three months

Interventions

Lenzumestrocel

Single cycle administration group : injections twice in a 26-day interval Multiple administration group : injections twice in a 26-day interval followed by repeated three times injections every three months

Intervention Type: BIOLOGICAL

Riluzole

concomitant administration of Riluzole to all groups, except subjects to whom Riluzole administration is deemed impossible owing to adverse events as determined by medical experts

Intervention Type: DRUG

Placebo Comparator

Single cycle administration group: Placebo comparator is injected three times every three months after injection of Lenzumestrocel twice in a 26-day interval.

Control group: Placebo comparator is injected twice in a 26-day interval followed by repeated three times injcections every three months

Intervention Type: DRUG

Other Intervention Names

Neuronata-R inj; Autologous Bone Marrow derived Mesenchymal Stem Cell; Rilutek; Normal Saline Inj.

Eligibility Criteria

Inclusion Criteria

1. Subjects who show both upper motor neuron signs and lower motor neuron signs at the same time in neurological tests.

2. Among subjects diagnosed with familial or sporadic ALS, subjects falling into clinically definite ALS, probable ALS and probable ALS-lab supported according to The revised World Federation of Neurology El Escorial Criteria[Rix Brooks, 2000], during 17-weeks period prior to the administration and ALSFRS-R score (progression rate) of 1.03 ± 50%/month (meaning mean value in that total period).

3. For subjects who are under Riluzole treatment, those who have received stable dose of Riluzole for more than 28 days before screening visit.

4. Subjects with duration of disease of no more than 2 years from the first diagnosis date.

5. Subjects whose ALSFRS-R scores are in the range of 31~46 at the time of screening (P-V0).

Exclusion Criteria

1. Subjects who received tracheostomy or use ventilators (including positive pressure ventilators; subjects who use non-invasive ventilation for sleep apnea may be allowed after review) at the time of screening (P-V0).

2. Subjects who received gastrotomy at the time of screening (P-V0).

3. Subjects for whom clinical efficacy evaluation is not possible because pulmonary functional tests cannot be conducted at the time of screening (P-V0) or subjects whose forced vital capacity is found to be not greater than 40%of the expected value.

4. Subjects who fall into above Class II according to the New York Heart Association's functional classification, 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 (P-V0) or who received stent insertion or coronary artery bypass grafting.

5. Subjects who have received other investigational products or edaravone within 3 month or 5 half-lives at the time of screening (P-V0) and lead in period visit L-V1 (evaluated by whichever is longer).

6. Subjects who have experienced epileptic seizure.

7. Subjects with severe renal disorder (serum creatinine: not less than 2.0 mg/dL).

8. Subjects with severe hepatic disorder (ALT, AST, or bilirubin: over 2.0 times of the normal upper limit).

9. Subjects who show hemorrhagic tendency at the time of screening (PT and aPTT > 1.5 x ULN)

10. Subjects who are found to have active viral infections (HBsAg, HCV Ab, HIV Ab, CMV IgM, EBV IgM, HSV IgM and Treponema pallidum) at the time of screening.

11. Subjects with hypersensitivity to antibiotics (penicillin or streptomycin).

12. Subjects who have ever received any cell therapy product for the same disease.

13. Subjects with any malignant tumor in the past 5 years before screening, except malignant tumors with very low risk of metastasis or death.

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Corestemchemon, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Seung Hyun Kim, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hanyang University Seoul Hospital

Locations

Pusan National University Yangsan Hospital

Yangsan, Kyungsangnam-do, South Korea

Hanyang university hospital

Seoul, Seoul, South Korea

Korea University Anam Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Countries

South Korea

References

Nam JY, Lee TY, Kim K, Chun S, Kim MS, Shin JH, Sung JJ, Kim BJ, Kim BJ, Oh KW, Kim KS, Kim SH. Efficacy and safety of Lenzumestrocel (Neuronata-R(R) inj.) in patients with amyotrophic lateral sclerosis (ALSUMMIT study): study protocol for a multicentre, randomized, double-blind, parallel-group, sham procedure-controlled, phase III trial. Trials. 2022 May 18;23(1):415. doi: 10.1186/s13063-022-06327-4.

Reference Type: DERIVED

PMID: 35585556 (View on PubMed)

Other Identifiers

NEURONATA-R_ALS301

Identifier Type: -

Identifier Source: org_study_id