Clinical trial NCT04745299: Evaluation the Efficacy and Safety of Mutiple Lenzumestrocel (Neuronata-R® Inj.) Treatment in Patients with ALS
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Amyotrophic Lateral Sclerosis
Keywords: Amyotrophic lateral sclerosis
Mesenchymal stem cell
cell therapy
ALS
neuroprotection
Phase 3 clinical trial
Lead sponsor: Corestemchemon, Inc.
Sponsor class: INDUSTRY
First posted: 2021-02-09
Enrollment: 115
Sex: ALL
Minimum age (years): 25
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Joint rank scores (CAFS, Combined Assessment of Functional and Survival)
timeFrame: at 12 months, and 6 months
Secondary outcomes:
measure: Joint rank scores (CAFS, Combined Assessment of Functional and Survival)
timeFrame: at 6 months
measure: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score
timeFrame: at 12 months, 6 months
measure: Time to event
timeFrame: at 12 months, 6 months
Other outcomes:
measure: Slow Vital Capacity (SVC)
timeFrame: 6 months, 12 months, 36 months
measure: Muscular strength
timeFrame: 6 months, 12 months, 36 months
measure: Time to event
timeFrame: 36 months
measure: Time to death
timeFrame: 6 months, 12 months, 36 months
measure: EuroQol Short Form (EQ-5D-5L)
timeFrame: 6 month, 12 months, 36 months
measure: Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40)
timeFrame: 6 month, 12 months, 36 months
measure: Biological test
timeFrame: up to 12 months after administration
Locations:
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
state: Kyungsangnam-do
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang university hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Hanyang University Seoul Hospital
name: Seung Hyun Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.