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

Primary Purpose

Amyotrophic Lateral Sclerosis

Status

Active

Phase

Phase 3

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Lenzumestrocel

Riluzole

Placebo Comparator

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring Amyotrophic lateral sclerosis, Mesenchymal stem cell, cell therapy, ALS, neuroprotection, Phase 3 clinical trial

Eligibility Criteria

25 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

[Inclusion Criteria]

Subjects who show both upper motor neuron signs and lower motor neuron signs at the same time in neurological tests.
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).
For subjects who are under Riluzole treatment, those who have received stable dose of Riluzole for more than 28 days before screening visit.
Subjects with duration of disease of no more than 2 years from the first diagnosis date.
Subjects whose ALSFRS-R scores are in the range of 31~46 at the time of screening (P-V0).

[Exclusion Criteria]

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).
Subjects who received gastrotomy at the time of screening (P-V0).
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.
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.
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).
Subjects who have experienced epileptic seizure.
Subjects with severe renal disorder (serum creatinine: not less than 2.0 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 (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 who have ever received any cell therapy product for the same disease.
Subjects with any malignant tumor in the past 5 years before screening, except malignant tumors with very low risk of metastasis or death.

Sites / Locations

Pusan National University Yangsan Hospital
Korea University Anam Hospital
Hanyang university hospital
Samsung Medical Center
Seoul National University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Single cycle administration group

Multiple administation group

Control group

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Joint rank scores (CAFS, Combined Assessment of Functional and Survival)

Joint rank score is derived from Combined Assessment of Function and Survival. Functional assessment is based on ALSFRS-R scores and survival assessment is based on the period from randomization to physical death. Joint rank score will be calculated with ALSFRS-R score data and survival. For each pairwise comparison, a study participant is assigned a score and then the summed scores are ranked for all participants. The higher ranking, the higher score, and the lower ranking, the lower score. And the average rank score is then calculated for each treatment group. A higher mean rank score indicates that participants in that treatment group, on average, fared better. The difference in joint rank scores between multiple administration group and control group at 12 months. The difference in joint rank scores between single cycle administration group and control group at 6 months

Secondary Outcome Measures

Joint rank scores (CAFS, Combined Assessment of Functional and Survival)

Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score

ALSFRS-R is an instrument designed to evaluate functional status of subjects with amyotrophic lateral sclerosis (Lou Gehrig's disease), such as gross motor activity, fine motor activity, bulbar function and respiration function. It consists of 12 items; 3 items for mouth functions, 4 items for upper limb and overall fine motor functions, 2 items for lower limb functions and 3 items for respiration functions. Each item is evaluated in 5-point scale (0~4). A higher score means a better functional status. Change of ALSFRS-R score measured at baseline and 12 months (multiple administration group and control group) Change of ALSFRS-R score measured at baseline and 6 months (single cycle administration and control group)

Time to event

Time to Event is defined as physical death, tracheostomy recognized as the point where disease progression functionally stops or chronic use of ventilator, whichever comes earlier. Chronic use of ventilator means that ventilator is used for more than 20 hours in a day and such use is continued for more than 30 days and that a subject in vegetative state requires full supports from other persons to maintain living. Time to event for 12 months (multiple administration group and control group) Time to event for 6 months (single cycle administration group and control group)

Full Information

NCT ID

NCT04745299

First Posted

January 27, 2021

Last Updated

July 25, 2023

Sponsor

Corestemchemon, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04745299

Brief Title

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

Acronym

ALSummit

Official Title

A Double-blind, Randomized, Multicenter, Placebo-Controlled, Parallel, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Lenzumestrocel(Neuronata-R® Inj.) in Patients With Amyotrophic Lateral Sclerosis

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

March 23, 2021 (Actual)

Primary Completion Date

October 30, 2023 (Anticipated)

Study Completion Date

May 3, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Corestemchemon, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic lateral sclerosis, Mesenchymal stem cell, cell therapy, ALS, neuroprotection, Phase 3 clinical trial

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

115 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Single cycle administration group

Arm Type

Experimental

Arm Description

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

Arm Title

Multiple administation group

Arm Type

Experimental

Arm Description

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

Arm Title

Control group

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

Lenzumestrocel

Other Intervention Name(s)

Neuronata-R inj, Autologous Bone Marrow derived Mesenchymal Stem Cell

Intervention Description

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

Drug

Intervention Name(s)

Riluzole

Other Intervention Name(s)

Rilutek

Intervention Description

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

Intervention Name(s)

Placebo Comparator

Other Intervention Name(s)

Normal Saline Inj.

Intervention Description

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

Primary Outcome Measure Information:

Title

Joint rank scores (CAFS, Combined Assessment of Functional and Survival)

Description

Time Frame

at 12 months, and 6 months

Secondary Outcome Measure Information:

Title

Joint rank scores (CAFS, Combined Assessment of Functional and Survival)

Description

Time Frame

at 6 months

Title

Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score

Description

Time Frame

at 12 months, 6 months

Title

Time to event

Description

Time Frame

at 12 months, 6 months

Other Pre-specified Outcome Measures:

Title

Slow Vital Capacity (SVC)

Description

Change to SVC measured at 6, 12 months and 36 months

Time Frame

6 months, 12 months, 36 months

Title

Muscular strength

Description

Change of Muscular strength which is measured by Hand Held Dynamometer (HHD)

Time Frame

6 months, 12 months, 36 months

Title

Time to event

Description

Time to event for 36 months

Time Frame

36 months

Title

Time to death

Description

Time to death means the period from randomization of a subject to physical death. The comparison with the time to death between treatment groups and control group.

Time Frame

6 months, 12 months, 36 months

Title

EuroQol Short Form (EQ-5D-5L)

Description

EQ-5D-5L is designed to measure health conditions and it consists of 5 questions relating to mobility, self-care, usual activities, pain/discomfort and anxiety/depression. 1~5 points are given for each question and a higher score means worse condition. Change of EQ-5D-5L from baseline to 6 month, 12 months, and 36 months.

Time Frame

6 month, 12 months, 36 months

Title

Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40)

Description

ALSAQ-40 is designed to evaluate disease-specific health conditions of subjects with ALS/motor neural disease. It consists of 40 questions to evaluate 5 aspects of health conditions affected by the disease. Subjects are asked to think about the difficulties they may have experienced during the last 2 weeks. Subjects are asked to indicate the frequency of each event by selecting one of 5 options (0~4): never/rarely/sometimes/often/always or cannot do at all.

Time Frame

6 month, 12 months, 36 months

Title

Biological test

Description

Tests on blood samples and cerebrospinal fluid samples for exploratory investigation of biological markers in plasma, blood and CSF. Comparison of change before and after treatment. Measurement cytokines : TGF-β1, IL-10, IL-6, TNF-α, MCP-1, IL-8, IL-1RA, MIP-1β, RANTES and IP-10 etc. Units of Measure: pg/mL Comparative Analysis of how much each cytokine increases or decreases after treatment compared to before treatment.

Time Frame

up to 12 months after administration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

25 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

[Inclusion Criteria] Subjects who show both upper motor neuron signs and lower motor neuron signs at the same time in neurological tests. 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). For subjects who are under Riluzole treatment, those who have received stable dose of Riluzole for more than 28 days before screening visit. Subjects with duration of disease of no more than 2 years from the first diagnosis date. Subjects whose ALSFRS-R scores are in the range of 31~46 at the time of screening (P-V0). [Exclusion Criteria] 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). Subjects who received gastrotomy at the time of screening (P-V0). 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. 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. 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). Subjects who have experienced epileptic seizure. Subjects with severe renal disorder (serum creatinine: not less than 2.0 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 (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 who have ever received any cell therapy product for the same disease. Subjects with any malignant tumor in the past 5 years before screening, except malignant tumors with very low risk of metastasis or death.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Seung Hyun Kim, MD, PhD

Organizational Affiliation

Hanyang University Seoul Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Pusan National University Yangsan Hospital

City

Yangsan

State/Province

Kyungsangnam-do

ZIP/Postal Code

50612

Country

Korea, Republic of

Facility Name

Korea University Anam Hospital

City

Seoul

ZIP/Postal Code

02841

Country

Korea, Republic of

Facility Name

Hanyang university hospital

City

Seoul

ZIP/Postal Code

04763

Country

Korea, Republic of

Facility Name

Samsung Medical Center

City

Seoul

ZIP/Postal Code

06351

Country

Korea, Republic of

Facility Name

Seoul National University Hospital

City

Seoul

Country

Korea, Republic of

12. IPD Sharing Statement

Citations:

PubMed Identifier

35585556

Citation

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.

Results Reference

derived

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

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