Clinical trial NCT00444613: A Study in Patients With Amyotrophic Lateral Sclerosis (ALS)
Official title: A Phase II/III Study in Patients With Amyotrophic Lateral Sclerosis (ALS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Amyotrophic Lateral Sclerosis (ALS)
Keywords: Amyotrophic Lateral Sclerosis (ALS)
motor neurons
muscular atrophy
Lou Gehrig's Disease
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2007-03-08
Enrollment: 373
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the efficacy and confirm the safety of E0302 in patients with Amyotrophic Lateral Sclerosis (ALS) by assessing changes in scores of survival rate and functional rating scale.


Eligibility criteria: Inclusion Criteria:

1. Patients who are able to submit written informed consent. If patients are duly capable of study consent but are unable to sign (or affix a seal) by themselves due to aggravation of disease condition, written informed consent can be obtained from a legally authorized representative who can sign on behalf of the patients after confirming the patients' agreement to study participation.
2. Patients who are aged 20 years or older at the time of obtaining informed consent.
3. Patients who have clinically definite ALS, clinically probable ALS, or clinically probable-laboratory supported ALS as specified in the revised El Escorial Airlie House diagnostic criteria.
4. Patients who are at stage 1 or 2 of the severity criteria for ALS.
5. Patients within 3-year elapsed time period from disease onset at the start of observation period.
6. Patients who can visit study site for out-patient treatment.

Exclusion Criteria:

1. Patients who underwent tracheostomy.
2. Patients who experienced non-invasive positive pressure ventilation.
3. Patients whose percent-predicted forced vital capacity (%FVC) is \>=60%.
4. Patients with multiple disturbances of conduction detected by nerve conduction test.
5. Patients with neurological symptom(s) due to vitamin B12 deficiency.
6. Patients who initiated newly introduced riluzole therapy after starting the observation period. Or those who received dose escalation or resumed administration of riluzole therapy after previous down titration or discontinuation.
7. Patients with cognitive impairment.
8. Pregnant women or women with a possibility of becoming pregnant.
9. Patients or their partners who are not willing to use reliable contraception.
10. Patients with severe disease in the renal, cardiovascular, hematological, or hepatic system (severe disease will be judged referring to "Ministry of Health, Labor and Welfare" (MHLW) Drug Safety Dept. Notification No. 80, Drug Safety Classification Criteria for Severity of Adverse Drug Reaction by Medicinal Products, Grade 3).
11. Patients with malignant tumor.
12. Patients who participated in another clinical study within 12 weeks before starting the observation period.
13. Patients with present illness or history of drug allergy or severe allergic disease (anaphylactic shock).
14. Patients who are judged to be ineligible for study entry by the investigator or subinvestigator.

Primary outcomes:
measure: Survival rate
timeFrame: Every 3 months.
measure: Functional rating scale.
timeFrame: Every 3 months.
Secondary outcomes:
measure: Manual Muscle Test (MMT)
timeFrame: Every 3 months.
measure: Percent-predicted forced vital capacity (%FVC)
timeFrame: Every 3 months.
Other outcomes:
Locations:
city: Nagoya-shi
country: Japan
state: Aichi
city: Akita-shi
country: Japan
state: Akita
city: Aomori-shi
country: Japan
state: Aomori
city: Chiba-shi
country: Japan
state: Chiba
city: Touon-shi
country: Japan
state: Ehime
city: Fukuoka-shi
country: Japan
state: Fukuoka
city: Kitakyusyu-shi
country: Japan
state: Fukuoka
city: Fukushima-shi
country: Japan
state: Fukushima
city: Maebashi-shi
country: Japan
state: Gunma
city: Higashihiroshima-shi
country: Japan
state: Hiroshima
city: Miyoshi-shi
country: Japan
state: Hiroshima
city: Otake-shi
country: Japan
state: Hiroshima
city: Sapporo-shi
country: Japan
state: Hokkaido
city: Kanazawa-shi
country: Japan
state: Ishikawa
city: Ichinoseki-shi
country: Japan
state: Iwate
city: Sagamihara-shi
country: Japan
state: Kanagawa
city: Yokohama-shi
country: Japan
state: Kanagawa
city: Nangoku-shi
country: Japan
state: Kochi
city: Kyoto-shi
country: Japan
state: Kyoto
city: Tsu-shi
country: Japan
state: Mie
city: Sendai-shi
country: Japan
state: Miyagi
city: Watari-gun
country: Japan
state: Miyagi
city: Nagano-shi
country: Japan
state: Nagano
city: Higashisonogi-gun
country: Japan
state: Nagasaki
city: Kashiwazaki-shi
country: Japan
state: Niigata
city: Niigata-shi
country: Japan
state: Niigata
city: Tsukubo-gun
country: Japan
state: Okayama
city: Ginowan-shi
country: Japan
state: Okinawa
city: Toyonaka-shi
country: Japan
state: Osaka
city: Hasuda-shi
country: Japan
state: Saitama
city: Saitama-shi
country: Japan
state: Saitama
city: Otsu-shi
country: Japan
state: Shiga
city: Hamamatsu-shi
country: Japan
state: Shizuoka
city: Shizuoka-shi
country: Japan
state: Shizuoka
city: Shimotsuke-shi
country: Japan
state: Tochigi
city: Tokushima-shi
country: Japan
state: Tokushima
city: Yoshinogawa-shi
country: Japan
state: Tokushima
city: Bunkyo-ku
country: Japan
state: Tokyo
city: Kodaira-shi
country: Japan
state: Tokyo
city: Ota-ku
country: Japan
state: Tokyo
city: Wakayama-shi
country: Japan
state: Wakayama
city: Yonezawa-shi
country: Japan
state: Yamagata
city: Shimonoseki-shi
country: Japan
state: Yamaguchi
city: Yanai-shi
country: Japan
state: Yamaguchi
Study officials:
affiliation: Neuroscience Clinical Development Section. JAC PCU. Eisai Co., Ltd.
name: Kazunori Saeki
role: STUDY_DIRECTOR
References:
citation: Kaji R, Imai T, Iwasaki Y, Okamoto K, Nakagawa M, Ohashi Y, Takase T, Hanada T, Shimizu H, Tashiro K, Kuzuhara S. Ultra-high-dose methylcobalamin in amyotrophic lateral sclerosis: a long-term phase II/III randomised controlled study. J Neurol Neurosurg Psychiatry. 2019 Apr;90(4):451-457. doi: 10.1136/jnnp-2018-319294. Epub 2019 Jan 13.
citation: Ikeda K, Iwasaki Y, Kaji R. Neuroprotective effect of ultra-high dose methylcobalamin in wobbler mouse model of amyotrophic lateral sclerosis. J Neurol Sci. 2015 Jul 15;354(1-2):70-4. doi: 10.1016/j.jns.2015.04.052. Epub 2015 May 8.