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A single-center, exploratory clinical trial evaluating the safety and efficacy of CL2020 in patients with amyotrophic lateral sclerosis (A single-center, exploratory clinical trial evaluating the safety and efficacy of CL2020 in patients with amyotrophic lateral sclerosis)

An exploratory clinical trial of CL2020 in patients with amyotrophic lateral sclerosis

5

Subjects aged 20 to 80 years, inclusive, with a diagnosis of sporadic or familial ALS that meets the definition, probable, or probable-laboratory supported of the Updated Awaji Criteria with an ALS severity of Grade 1 or 2. (At baseline, the age of the subjects of the clinical research was 57.6 +/- 8.9 years (mean +/- SD), 3 males (60.0%), 3 subjects (60.0%) had received riluzole, and ALSFRS-R total score was 40.6 +/- 2.6 (mean +/- SD).)

Informed consent was obtained from 6 subjects, and 5 subjects excluding 1 ineligible subject received 6 doses of CL2020 and completed the observation period.

No death occurred during the observation period. The serious adverse event was 1 event of limb fracture in 1 subject. The event was not related to the study product.

As for safety up to Week 24, there were no deaths, serious adverse events, or adverse events leading to treatment discontinuation during treatment with CL2020. ALSFRS-R The change in total score tended to decrease over time, but tended to improve at Week 52 of initial administration (beta = -0.25) compared to Week 12 before administration of CL2020 (beta = -0.47). As for other efficacy endpoints, the change in the total MMT score (Baseline, 53.2 +/- 4.4, 95% CI = 47.7-58.7; 24 weeks after first dose, 51.0 +/- 4.2, 95% CI = 45.7-56.3, P = 0.004; 52 weeks after first dose, 47.3 +/- 3.8, 95% CI = 41.2-53.3, P = 0.009), the change in the total Modified Norris Scale score (Baseline, 88.4 +/- 5.0, 95% CI = 82.2-94.6; 24 weeks after first dose, 83.8 +/- 13.0, 95% CI = 67.6-100.0, P = 0.119; 52 weeks after first dose, 79.4 +/- 14.0, 95% CI = 62.0-96.8, P = 0.042), and the change in the total ALSAQ-40 score (Baseline, 75.6 +/- 14.9, 95% CI = 57.1-94.1; 4 weeks after first dose, 67.4 +/- 10.9, 95% CI = 53.8-81.0, P < 0.001; 24 weeks after first dose, 79.6 +/- 16.0, 95% CI = 59.7-99.5, P = 0.192; 52 weeks after first dose, 94.4 +/- 18.5, 95% CI = 71.4-117.4, P = 0.002), the indices or subscores evaluating limb function tended to worsen over time, supporting the results of changes in the total ALSFRS-R score.

There were no safety concerns associated with multiple doses of CL2020 in ALS patients. In patients with a change in ALSFRS-R score from baseline of -1 to -2 during the screening period (12 weeks), multiple-dose administration of CL2020 was shown to prevent symptoms from worsening in ALS patients.

Jan. 10, 2024

Nov. 28, 2023

https://journals.sagepub.com/doi/full/10.1177/09636897231214370

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2063200047

Fukushima Tatsunobu

Life Science Institute, Inc.

1-1 Marunouchi 1-chome, Chiyoda-ku, Tokyo 100-8251

lsii.chiken-inq@eppharmaline.co.jp

Call center

Life Science Institute, Inc.

1-1 Marunouchi 1-chome, Chiyoda-ku, Tokyo 100-8251

+81-3-6748-7200

lsii.chiken-inq@eppharmaline.co.jp

Complete

Feb. 08, 2021

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

(1) Patients with new onset or within 2 years after onset at the start of screening
(2) Patients with 1 or 2 severity according to ALS severity criteria
(3) Subjects who can receive treatment on an outpatient basis

(1) Patients undergoing tracheostomy
(2) Patients who have worn non-invasive respiratory assist device
(3) Patients with% FVC of 80% or less
(4) Patients with chronic obstructive pulmonary disease (COPD)
(5) Patients with impaired respiratory function who complained of dyspnea at the end of screening(ALS FRS-R:10. Dyspnea, 11. Orthopnea, 12. Respiratory failure, any of those 3 items is 3 points or less)
(6) Patients using Edaravone injection within 4 weeks before the start of screening
(7) Patients who started taking Riluzole, or patients who changed or discontinued the dose after obtaining informed consent
(8) Patients with cognitive dysfunction (Alzheimer's disease and other dementia, Parkinson's disease, or other neurological disorders, etc.) that principal investigator/sub investigator has determined to affect their ability to participate in this trial or the evaluation of the clinical trial
(9) Patients with a history of surgery on the spine such as cervical spondylosis and herniated disc after the onset of ALS, or patients scheduled for surgery during the clinical trial period
(10) Patients who could not rule out the possibility of diseases symptoms that require differential diagnosis such as cervical spondylosis and multifocal motor neuropathy
(11) Patients with serious respiratory, cardiovascular or hepato-renal disorders
(12) Patients with complication of malignant tumor or history of it (however, patients who in
remission for 5 years could be included)
(13) Patients with collagen disease and related diseases
(14) Patients with severe diabetes mellitus (HbA1C >10%)
(15) Patients with active infectious disease requiring medical treatment(including HB antigen, HCV antibody, HIV antibody, HTLV-1 antibody, Syphilis)
(16) Patients who received high-dose intravenous immunoglobulin therapy within 8 weeks before the start of screening
(17) Patients who are taking systemic steroid hormone or immunosuppressant drugs
(18) Patients who have been treated with bone marrow transplantation or stem cell therapy
(19) Patients who are pregnant/possibly pregnant or breastfeeding
(20) Male or female patients who could not agree to birth control explained by principal investigator/sub investigator from completion of informed consent until completion of observation period
(21) Patients with history of allergy to aminoglycoside antibiotics including kanamycin
(22) Patients with history of allergy to human serum albumin formula or xenogeneic-derived protein (cow and swine)
(23) Patients who participated in other clinical trials within 12 weeks before completion of informed consent for the clinical trial
(24) Patients with or with a history of drug allergies or severe allergic diseases (anaphylactic shock, etc.)
(25) Patients with severe complications that principal investigator/sub investigator judged as inappropriate
(26) Patients who the principal investigator/sub investigator judged as inappropriate to participate

Both

Amyotrophic Lateral Sclerosis

CL2020 once every 4 weeks, total of 6 intravenous doses

Safety and tolerability as measured by incidence of Adverse events (AEs), adverse drug reactions (ADRs)

+81-86-235-7534

Jan. 20, 2021

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