Clinical Trial Page

Summary
EudraCT Number:2021-003900-42
Sponsor's Protocol Code Number:MT-1186-A04
National Competent Authority:Italy - Italian Medicines Agency
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2022-09-06
Trial results
Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL
A. Protocol Information
A.1Member State ConcernedItaly - Italian Medicines Agency
A.2EudraCT number2021-003900-42
A.3Full title of the trial
A Phase 3b, Multicenter, Randomized, Double-blind Extension Study to Evaluate the Continued Efficacy and Safety of Oral Edaravone Administered for an Additional Period of up to 48 Weeks Following Study MT-1186-A02 in Subjects with Amyotrophic Lateral Sclerosis (ALS)
Studio di estensione di fase IIIb, multicentrico, randomizzato, in doppio cieco per valutare il mantenimento dell’efficacia e della sicurezza di edaravone orale somministrato per un periodo aggiuntivo fino a 48 settimane dopo lo studio MT-1186-A02 a soggetti con sclerosi laterale amiotrofica (SLA)
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Continued Efficacy and Safety Study of Oral Edaravone Following Study MT-1186-A02 in Subjects with Amyotrophic Lateral Sclerosis (ALS)
Studio sull’efficacia e la sicurezza continuative di edaravone orale a seguito dello studio MT 1186-A02 in soggetti affetti da sclerosi laterale amiotrofica (SLA)
A.3.2Name or abbreviated title of the trial where available
-
-
A.4.1Sponsor's protocol code numberMT-1186-A04
A.5.4Other Identifiers
Name:IND numberNumber:138145
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorMitsubishi Tanabe Development America Inc.
B.1.3.4CountryUnited States
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportMitsubishi Tanabe Pharma Development America, Inc.
B.4.2CountryUnited States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationMitsubishi Tanabe Pharma Development America, Inc.
B.5.2Functional name of contact pointDaniel Selness
B.5.3 Address:
B.5.3.1Street Address525 Washington Boulevard, Suite 400
B.5.3.2Town/ cityJersey City
B.5.3.3Post codeNJ 07310
B.5.3.4CountryUnited States
B.5.4Telephone number0014147048829
B.5.6E-maildaniel_selness@mt-pharma-us.com
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameEdaravone
D.3.2Product code [MT-1186]
D.3.4Pharmaceutical form Oral suspension
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPGastroenteral use
Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNEdavarone
D.3.9.1CAS number 89-25-8
D.3.9.2Current sponsor codeMT-1186
D.3.9.4EV Substance CodeSUB06453MIG
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number21
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
D.3.11.3.2Gene therapy medical product Information not present in EudraCT
D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
D.8 Placebo: 1
D.8.1Is a Placebo used in this Trial?Yes
D.8.3Pharmaceutical form of the placeboOral suspension
D.8.4Route of administration of the placeboOral use
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Amyotrophic Lateral Sclerosis (ALS)
Sclerosi Laterale Amiotrofica (SLA)
E.1.1.1Medical condition in easily understood language
A disease that affects nerve cells in the brain and the spinal cord.
Una malattia che colpisce le cellule nervose nel cervello e nel midollo spinale
E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.1
E.1.2Level PT
E.1.2Classification code 10002026
E.1.2Term Amyotrophic lateral sclerosis
E.1.2System Organ Class 10029205 - Nervous system disorders
E.1.3Condition being studied is a rare disease Yes
E.2 Objective of the trial
E.2.1Main objective of the trial
To evaluate and compare the efficacy of the following two dosing regimens of oral Edaravone in subjects with amyotrophic lateral sclerosis (ALS) based on the time from the randomization date in Study MT-1186-A02 to at least a 12-point decrease in Revised ALS Functional Rating Score (ALSFRS-R) or death, whichever happens first, over the course of the study or until the oral Edaravone is commercially available in that country:
- Oral Edaravone 105 mg administered once daily
- Oral Edaravone 105 mg administered for 10 days followed by placebo for 18 days (regimen denoted as on/off).
Valutare e confrontare l’efficacia dei seguenti due regimi di dosaggio di edaravone orale in soggetti con sclerosi laterale amiotrofica (SLA) in base al tempo trascorso dalla data di randomizzazione nello Studio MT-1186-A02 a una riduzione di almeno 12 punti nel punteggio della scala ALS Functional Rating Scale-Revised (ALSFRS-R) o al decesso, in base all’evento che si verificherà per primo, nel corso dello studio o finché edaravone orale sarà disponibile in commercio nel Paese interessato:
-Edaravone orale 105 mg somministrato una volta al giorno
-Edaravone orale 105 mg somministrato per 10 giorni, seguito da placebo per 18 giorni (regime indicato come on/off).
E.2.2Secondary objectives of the trial
To evaluate the safety and tolerability of oral Edaravone at a dose of 105 mg once daily compared to oral Edaravone at a dose of 105 mg including placebo (regimen denoted as on/off) in subjects with ALS over the course of the study or until oral Edaravone is commercially available in that country .
Valutare la sicurezza e la tollerabilità di edaravone orale alla dose di 105 mg una volta al giorno rispetto a edaravone orale alla dose di 105 mg incluso placebo (regime indicato come on/off) in soggetti con SLA nel corso dello studio o finché edaravone orale sarà disponibile in commercio nel Paese interessato.
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
Subjects who meet all of the following criteria will be considered eligible to participate in Study MT-1186-A04:

1. Subjects must provide a signed and dated informed consent form to participate in the study.
2. Subjects must be able (in the judgment of the Investigator) to understand the nature of the study and all risks involved with participation in the study.
3. Subjects must be willing to cooperate and comply with all protocol restrictions and requirements.
4. Subjects must have successfully completed all Study MT-1186-A02 visits and have been compliant with study drug.
I soggetti che soddisfano i seguenti criteri saranno considerati eleggibili a partecipare allo Studio MT-1186-A04:

1. i soggetti devono fornire un modulo di consenso informato firmato e datato per poter partecipare allo studio;
2. i soggetti devono essere in grado (secondo il parere dello Sperimentatore) di comprendere la natura dello studio e tutti i rischi che comporta la partecipazione;
3. i soggetti devono essere disposti a collaborare e attenersi alle restrizioni e ai requisiti del protocollo;
4. i soggetti devono aver completato con esito positivo tutte le visite dello Studio MT-1186-A02 e aver aderito al trattamento con il farmaco in studio.
E.4Principal exclusion criteria
Subjects who meet any of the following criteria will be excluded from the study:
1. Subjects of childbearing potential unwilling to use an acceptable method of contraception from the screening visit until 3 months after the last dose of study medication. Subjects who are sexually active who do not agree to use contraception during the study period. Refer to Appendix 3 for additional contraceptive information.
2. Subjects who are female, of childbearing potential, and pregnant (a positive pregnancy test) or lactating at the screening visit.
3. Subjects who have a significant risk of suicide. Subjects with any suicidal behavior or suicidal ideation of type 4 (active suicidal ideation with some intent to act, without a specific plan) or type 5 (active suicidal ideation with specific plan and intent) based on the Columbia-Suicide Severity Rating Scale (C-SSRS) at Week 48 of Study MT-1186-A02.
4. Subjects who are not eligible to continue in the study, as judged by the Investigator in conjunction with the MTDA medical monitor.
5. Subjects who are unable to take their medications orally or through a PEG/RIG tube.
I soggetti che soddisfano uno qualsiasi dei seguenti criteri saranno esclusi dallo studio:
1. soggetti in grado di procreare non disposti a utilizzare un metodo contraccettivo accettabile a partire dalla visita di screening e fino a 3 mesi dopo l’assunzione dell'ultima dose di farmaco in studio. Soggetti sessualmente attivi che non acconsentono a usare un metodo di contraccezione durante il periodo dello studio. Per ulteriori informazioni riguardo alla contraccezione, consultare l’Appendice 3 del protocollo;
2. soggetti di sesso femminile, in età fertile e in stato di gravidanza (un test di gravidanza positivo) o che allattano con latte materno alla visita di screening;
3. soggetti che presentano un rischio suicidario significativo. Soggetti che presentano qualsiasi comportamento suicidario o ideazione suicidaria di tipo 4 (ideazione suicidaria attiva con intenzione di agire, senza un piano specifico) o di tipo 5 (ideazione suicidaria attiva con un piano e un’intenzione specifici) in base alla scala di valutazione della gravità della suicidalità della Columbia University (C-SSRS) alla Settimana 48 dello Studio MT-1186-A02;
4. soggetti che, secondo il parere dello Sperimentatore in collaborazione con il monitor medico di MTDA, non sono idonei a continuare nello studio;
5. soggetti che non sono in grado di assumere il proprio farmaco per via orale o mediante sonda PEG/RIG.
E.5 End points
E.5.1Primary end point(s)
- Time from the randomization date in Study MT-1186-A02 to at least a 12-point decrease in ALSFRS-R or death, whichever happens first.
- Tempo dalla data di randomizzazione nello Studio MT-1186-A02 a una riduzione di almeno 12 punti nel punteggio della scala ALSFRS-R o al decesso, in base all’evento che si verifica prima.
E.5.1.1Timepoint(s) of evaluation of this end point
End of treatment visit number 5 (week 48)
Visita di fine trattamento numero 5 (settimana 48)
E.5.2Secondary end point(s)
- The Combined Assessment of Function and Survival (CAFS) score at Weeks 24 and 48 in Study MT-1186-A04
- Change in the Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 score from baseline in Study MT-1186-A02 to Weeks 24 and 48 in Study MT-1186-A04.
- Change in ALSFRS-R score from baseline in Study MT-1186-A02 to Weeks 12, 24, 36 and 48 in Study MT-1186-A04.
- Time from the randomization date in Study MT-1186-A02 to death, tracheostomy or permanent assisted mechanical ventilation (= 23 hours/day).
- Punteggio della valutazione combinata di funzione e sopravvivenza (CAFS) alle Settimane 24 e 48 nello Studio MT-1186-A04
- Variazione del punteggio del Questionario di valutazione della sclerosi laterale amiotrofica a 40 elementi dal basale nello Studio MT-1186-A02 alle Settimane 24 e 48 nello Studio MT-1186-A04
- Variazione del punteggio ALSFRS-R dal basale nello Studio MT-1186-A02 alle Settimane 12, 24, 36 e 48 nello Studio MT-1186-A04
- Tempo dalla data di randomizzazione nello Studio MT-1186-A02 al decesso, tracheotomia o ventilazione meccanica assistita permanente (=23 ore/giorno)
E.5.2.1Timepoint(s) of evaluation of this end point
At various timepoints throughout the study as described above.
In diversi punti temporali durante il corso dello studio come descritto sopra.
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic Yes
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic Yes
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) Yes
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open No
E.8.1.3Single blind No
E.8.1.4Double blind Yes
E.8.1.5Parallel group Yes
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo Yes
E.8.2.3Other No
E.8.2.4Number of treatment arms in the trial2
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned7
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA21
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
Canada
Germany
Italy
Japan
Korea, Republic of
Switzerland
United States
E.8.7Trial has a data monitoring committee Yes
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
The end of the study is defined as the last visit for the last subject.
Il termine dello studio è definito come l’ultima visita dell’ultimo soggetto.
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years3
E.8.9.1In the Member State concerned months0
E.8.9.1In the Member State concerned days0
E.8.9.2In all countries concerned by the trial years3
E.8.9.2In all countries concerned by the trial months0
E.8.9.2In all countries concerned by the trial days0
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 150
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 150
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others Yes
F.3.3.7.1Details of other specific vulnerable populations
Male subjects with partners of child-bearing potential using contraception
Soggetti di sesso maschile con partner potenzialmente fertili che utilizzano un metodo contraccettiv
F.4 Planned number of subjects to be included
F.4.1In the member state19
F.4.2 For a multinational trial
F.4.2.1In the EEA 64
F.4.2.2In the whole clinical trial 300
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
N/A
N/A
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2022-05-17
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2022-06-13
P. End of Trial
P.End of Trial StatusOngoing

Sponsors and Collaborators

Medical Conditions

Drug Interventions

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