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    Summary
    EudraCT Number:2020-005522-28
    Sponsor's Protocol Code Number:ION363-CS1
    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:2021-08-09
    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
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2020-005522-28
    A.3Full title of the trial
    A Phase 1-3 Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION363 in Amyotrophic Lateral Sclerosis Patients with Fused in Sarcoma Mutations (FUS-ALS)
    Studio di Fase 1-3 per valutare l’efficacia, la sicurezza, la farmacocinetica e la farmacodinamica di ION363 somministrato per via intratecale in pazienti con sclerosi laterale amiotrofica con mutazioni del gene della proteina fusa nel sarcoma (FUS-SLA)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of ION363 in Amyotrophic Lateral Sclerosis Participants With Fused in Sarcoma Mutations (FUS-ALS).
    Studio per valutare l’efficacia, la sicurezza, la farmacocinetica e la farmacodinamica di ION363 in pazienti con sclerosi laterale amiotrofica con mutazioni del gene della proteina fusa nel sarcoma (FUS-SLA)
    A.3.2Name or abbreviated title of the trial where available
    FUSION: A Phase 1-3 study to evaluate the effects of ION363 in FUS-ALS patients
    FUSION: studio di fase 1-3 per valutare gli effetti di ION363 in pazienti FUS-ALS
    A.4.1Sponsor's protocol code numberION363-CS1
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04768972
    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 SponsorIONIS PHARMACEUTICALS, 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 supportIonis Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIonis Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointIonis Clinical Trial Information
    B.5.3 Address:
    B.5.3.1Street Address2855 Gazelle Court
    B.5.3.2Town/ cityCarlsbad
    B.5.3.3Post codeCA 92010
    B.5.3.4CountryUnited States
    B.5.4Telephone number+17606032302
    B.5.5Fax number+17606033891
    B.5.6E-mailtbaumann@ionisph.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 nameION363
    D.3.2Product code [ION363]
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntrathecal use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeION363
    D.3.9.3Other descriptive nameall-P-ambo-2'-O-(2-methoxyethyl)-P-thioguanylyl-(3'-O->5'-O)-2'-O-(2-methoxyethyl)-5-methylcytidylyl-(3'-O->5'-O)-2'-O-(2-methoxyethyl)adenylyl-(3'-O->5'-O)-2'-O-(2-methoxyethyl)adenylyl-(3'-O->5'-O)-2'-O-(2-methoxyethyl)-5-methyluridylyl-(3'-O->5'-O)-2'-deoxy-P-thioguanylyl-(3'-O->5'-O)-P-thiothymidylyl-(3'-O->5'-O)-2'-deoxy-5-methyl-P-thiocytidylyl-(3'-O->5'-O)-2'-deoxy-Pthioadenylyl-(3'-O->5'-O)-2'-deoxy-5-methyl-P-thiocytidylyl-(3'-O->5'-O)-2'-deoxy- 5-methyl-P-thiocytidylyl-(3'-O->5'-O)-P-t
    D.3.9.4EV Substance CodeSUB222715
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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 Yes
    D.3.11.13.1Other medicinal product typeAntisense Oligonucleotide
    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 placeboSolution for injection
    D.8.4Route of administration of the placeboIntrathecal 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 with Fused in Sarcoma mutations
    Sclerosi laterale amiotrofica con mutazioni del gene della proteina fusa nel sarcoma
    E.1.1.1Medical condition in easily understood language
    Amyotrophic Lateral Sclerosis
    Sclerosi laterale amiotrofica
    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 the clinical efficacy of ION363 in clinical functioning and survival in Amyotrophic Lateral Sclerosis (ALS) patients with Fused in Sarcoma mutations (FUS-ALS).
    Valutare l’efficacia clinica di ION363 nel funzionamento clinico e nella sopravvivenza in pazienti affetti/e da sclerosi laterale amiotrofica (SLA) con mutazioni del gene fuso in sarcoma (FUS-SLA).
    E.2.2Secondary objectives of the trial
    To further evaluate the effects of ION363 in halting, reversing, or slowing the deterioration of clinical functioning and biomarkers of disease severity in FUS-ALS patients.
    Valutare ulteriormente gli effetti di ION363 nell’interrompere, invertire o rallentare il deterioramento del funzionamento clinico e dei biomarcatori della gravità della malattia nei pazienti con FUS-SLA.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Inclusion Criteria for Part 1:
    1.Signs or symptoms consistent with an ALS disease process in the opinion of the Investigator
    2.Participants in:
    Cohort A must be, at the time of informed consent, 12 – 65 years of age, inclusive, with signs or symptoms consistent with an ALS disease process in the opinion of the Investigator and if 30 to 65 years of age, inclusive, have an ALSFRS-R pre-study slope = 0.4 points per month (calculated as [48-Screening ALSFRS-R score]/time in months since symptom onset)
    Cohort B must be, at the time of informed consent, > 30 years of age, with signs or symptoms consistent with an ALS disease process in the opinion of the Investigator and have an ALSFRS-R pre-study slope < 0.4 points per month (calculated as [48-Screening ALSFRS-R score]/time in months since symptom onset)
    3.Confirmed genetic mutation in FUS in a clinical laboratory improvement amendments (CLIA) certified, CE-marked, or equivalent testing laboratory and classified as "pathogenic" or "likely pathogenic".
    Mutations not pre-approved per the Variant Classification Manual must be reviewed and approved by a variant classification committee
    4.Upright (sitting position) slow vital capacity (SVC) as adjusted for sex, age, and height = 50 percentage (%) of predicted value
    5.Participants taking edaravone must be on a stable dose for = 28 days prior to Screening and riluzole must be on a stable dose for = 28 days prior to Day 1, and willing to continue on that dose throughout the duration of the study, unless the Investigator determines that it should be discontinued for medical reasons, in which case it may not be restarted during the study
    6.Stable concomitant medications and nutritional support for at least 1 month prior to Study Day 1. Concomitant medications or nutritional support that have not been stable for at least 1 month prior to Study Day 1 may be allowed in consultation with the Sponsor Medical Monitor or designee.
    7.Has an informant/caregiver who, in the Investigator's judgment, has frequent and sufficient contact with the participant as to be able to provide accurate information about the participant's cognitive and
    functional abilities at Screening. Participants < 18 years old at Screening must have a trial partner (parent, caregiver or other) who is reliable, competent and at least 18 years of age, is willing to accompany the participant to trial visits and to be available to the Study Center by phone if needed, and who (in the opinion of the Investigator) is and will remain sufficiently knowledgeable of participant's ongoing condition to respond to Study Center inquiries about the participant
    Inclusion Criteria for Part 2:
    1.Completed, or rescued from, Part 1, or
    2.Enrolled and received at least 1 dose of ION363 in the Investigator initiated EAP program
    3.Patient meeting Criteria #1-2 is otherwise suitable for study participation, in the opinion of the Investigator
    Criteri di inclusione per la Parte 1
    1. Segni o sintomi consistenti con il processo della malattia sclerosi laterale amiotrofica a giudizio dello Sperimentatore
    2. Pazienti in:
    Coorte A, al momento del consenso informato, devono avere un’età compresa tra 12 e 65 anni inclusi, con segni o sintomi coerenti con un processo della malattia SLA secondo il parere dello Sperimentatore e, se di età compresa tra 30 e 65 anni inclusi, avere una pendenza pre-studio ALSFRS-R =0,4 punti al mese (calcolata come [punteggio ALSFRS-R allo Screening di 48]/tempo in mesi dall’insorgenza dei sintomi).
    Coorte B, al momento del consenso informato, devono avere un’età >30 anni, con segni o sintomi coerenti con un processo della malattia SLA secondo il parere dello Sperimentatore e avere una pendenza pre-studio ALSFRS-R <0,4 punti al mese (calcolata come [punteggio ALSFRS-R allo Screening di 48]/tempo in mesi dall’insorgenza dei sintomi).
    3.Mutazione genetica confermata in FUS in un laboratorio di analisi certificato da Clinical Laboratory Improvement Amendments (CLIA), con marchio CE o equivalente, e preapprovato secondo il Manuale di classificazione delle varianti. Le mutazioni non preapprovate secondo il Manuale di classificazione delle varianti devono essere esaminate e approvate da un comitato di classificazione delle varianti.
    4.CVL in posizione eretta (seduta) regolata per sesso, età e altezza =50% del valore previsto.
    5. I/Le pazienti che assumono edaravone devono assumere una dose stabile per =28 giorni prima dello Screening, e che assumono riluzolo devono assumere una dose stabile per =28 giorni prima del Giorno 1 e devono essere disposti a continuare con tale dose per tutta la durata dello studio, a meno che lo Sperimentatore non stabilisca che deve essere interrotta per motivi medici, nel qual caso non potrà essere riavviata durante lo studio.
    6.Farmaci concomitanti stabili e supporto nutrizionale per almeno 1 mese prima del Giorno 1 dello studio. I farmaci concomitanti o il supporto nutrizionale che non sono rimasti stabili per almeno 1 mese prima del Giorno 1 dello studio possono essere consentiti a discrezione del Medical monitor dello Sponsor o designato.
    7. Ha una persona che fornisce le informazioni/caregiver che, a discrezione dello Sperimentatore, ha un contatto frequente e sufficiente con il/la partecipante per poter fornire informazioni precise sulle capacità cognitive e funzionali del/la partecipante allo Screening. I/Le pazienti di età <18 anni allo Screening devono avere un partner per la sperimentazione (genitore, caregiver o altro) che sia affidabile, competente e di almeno 18 anni, che sia disposto ad accompagnare il/la paziente alle visite della sperimentazione e che sia a disposizione del Centro dello studio per telefono se necessario, e che (a giudizio dello Sperimentatore) sia e rimanga sufficientemente a conoscenza delle condizioni attuali del/la paziente per rispondere alle domande sul/la paziente poste dal Centro dello studio.
    Criteri di inclusione per la Parte 2
    1. Aver completato la Parte 1 o essere stati recuperati da essa, oppure
    2. Essere stati arruolati e aver ricevuto almeno 1 dose di ION363 nel programma EAP avviato dallo Sperimentatore
    3. Il/La paziente che soddisfa i criteri n. 1-2 è diversamente idoneo/a alla partecipazione allo studio, secondo il parere dello Sperimentatore
    E.4Principal exclusion criteria
    Exclusion Criteria for Part 1:
    1.Requiring permanent ventilation (> 22 hours of mechanical ventilation [invasive or noninvasive] per day for > 21 consecutive days) and/or tracheostomy
    2.Any known ALS-associated mutations except FUS
    3.Positive test result for:
    a.Human immunodeficiency virus (HIV)
    b.Hepatitis C (HCV), unless previously treated and has been serum/plasma HCV RNA negative for at least 6 months after the end of treatment
    c.Hepatitis B (HBV) by HBV surface antigen test, unless currently on nucleotide/nucleoside analogue treatment
    4.Clinically significant (CS) abnormalities in medical history (e.g.,previous acute coronary syndrome within 3 months of Screening, major surgery within 2 months of Screening) or physical examination, unless discussed and approved by the Sponsor Medical Monitor
    5.Uncontrolled hypertension (blood pressure [BP] > 160/100 millimeters of mercury [mm Hg])
    6.Malignancy within 1 year of Screening, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated. Participants with a history of other malignancies that have been treated with curative intent and which have no recurrence within 6 months may also be eligible if approved by the Sponsor medical monitor
    7.Obstructive hydrocephalus
    8.Known significant brain or spinal disease that would interfere with the lumbar puncture (LP) process, CSF circulation or safety assessment, including tumors or abnormalities by magnetic resonance imaging (MRI) or computed tomography (CT), subarachnoid hemorrhage, suggestion of raised intracranial pressure on MRI or ophthalmic examination, spinal stenosis or curvature, chiari malformation, obstructive hydrocephalus, syringomyelia, tethered spinal cord syndrome and connective tissue disorders such as Ehlers-Danlos syndrome and Marfan syndrome
    9.Concurrent participation in any other interventional clinical study
    10.Previous treatment with an oligonucleotide (including small interfering RNA [siRNA]). This exclusion criterion does not apply to COVID-19 vaccinations, which are allowed
    11.Treatment with another investigational drug, biological agent, or device, including, but not limited to sodium phenylbutyrate, within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer
    12.History of gene therapy or cell transplantation or any other experimental brain surgery
    13.Have any other conditions, which, in the opinion of the Investigator would make the participant unsuitable for inclusion, or could interfere with the individual participating in or completing the study
    Criteri di esclusione per la Parte 1
    1. Necessità di ventilazione permanente (>22 ore di ventilazione meccanica [invasiva o non invasiva] al giorno per >21 giorni consecutivi) o tracheostomia
    2. Qualsiasi mutazione nota associata alla SLA, ad eccezione di FUS
    3. Risultato positivo del test per:
    a. Virus dell’immunodeficienza umana (HIV)
    b. Epatite C (HCV), a meno che non sia stata precedentemente trattata e che l’RNA del siero/plasma non sia risultato negativo all’HCV per almeno 6 mesi dopo la fine del trattamento
    c. Epatite B (HBV) mediante il test dell’antigene di superficie dell’HBV, a meno che non sia attualmente in trattamento con un analogo nucleotidico/nucleosidico
    4. Anomalie clinicamente significative (CS) nell’anamnesi medica (ad es. pregressa sindrome coronarica acuta entro 3 mesi dallo Screening, intervento di chirurgia maggiore entro 2 mesi dallo Screening) o nell’esame obiettivo a meno che discusse e approvate dal medical monitor dello Sponsor
    5. Ipertensione non controllata (PA >160/100 mmHg)
    6. Neoplasia maligna entro 1 anno dallo Screening, ad eccezione del carcinoma cutaneo basocellulare o a cellule squamose, o del carcinoma della cervice in situ trattato con successo. I pazienti con un’anamnesi di altre neoplasie maligne trattate con intento curativo e che non presentano una recidiva entro 6 mesi possono anch’essi essere idonei a discrezione del medical monitor dello Sponsor
    7. Idrocefalo ostruttivo
    8. Malattia cerebrale o spinale significativa nota che interferirebbe con il processo della PL, la circolazione del LCS o la valutazione della sicurezza, compresi i tumori o le anomalie mediante RM o tomografia computerizzata (TC), emorragia subaracnoidea, indicazione di aumento della pressione intracranica alla RM o all’esame oftalmico, stenosi o curvatura spinale, sindrome di Arnold-Chiari, idrocefalo ostruttivo, siringomielia, sindrome del midollo ancorato e disturbi del tessuto connettivo come la sindrome di Marfan
    9. Partecipazione simultanea a qualsiasi altro studio clinico interventistico
    10.Pregresso trattamento con un oligonucleotide (compreso siRNA). Questo criterio di esclusione non si applica alle vaccinazioni anti-COVID-19, che sono consentite
    11.Trattamento con un altro farmaco, agente biologico o dispositivo sperimentale, incluso a titolo esemplificativo, ma non esaustivo, il fenilbutirrato di sodio, entro 1 mese dallo Screening o 5 emivite dell’agente sperimentale, a seconda di quale dei due abbia la durata maggiore
    12.Anamnesi di terapia genica o trapianto di cellule o qualsiasi altro intervento chirurgico cerebrale sperimentale
    13. Presenza di qualsiasi altra condizione che, nell’opinione dello Sperimentatore, renderebbe il/la paziente inadatto/a all’inclusione o potrebbe interferire con la partecipazione del/la paziente allo studio o con il completamento di quest’ultimo
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is the evaluation of the effects of ION363 vs. placebo on change from Day 1 to Study Day 225 in Part 1 Cohort A in functional impairment, measured by joint rank analysis of the combined assessment of the following:
    • In-clinic Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score
    • Time of rescue or a discontinuation of Part 1 and entering Part 2 due to a marked deterioration in function. Rescue takes place if there is a deterioration relative to Baseline in ALSFRS-R score of > 10 points or a decline in slow vital capacity (SVC) of < 40% of predicted value at Study Day 141, or later, that is confirmed after an interval of 4 weeks. Rescue means the patient may discontinue Part 1 and enter Part 2 of the study
    • Ventilation assistance-free survival (VAFS), defined as the time to the earliest occurrence of 1 of the following events:
    o Death
    o Permanent ventilation (> 22 hours of mechanical ventilation [invasive or noninvasive] per day for > 21 consecutive days in the absence of an acute reversible event)
    L’endpoint primario è la valutazione degli effetti di ION363 rispetto al placebo sulla variazione dal Giorno 1 al Giorno 225 dello studio nella Coorte A della Parte 1 nella compromissione funzionale, misurata mediante analisi dei ranghi congiunti della valutazione combinata di quanto segue:
    • Punteggio totale della Scala di valutazione funzionale della sclerosi laterale amiotrofica-rivista (ALSFRS-R) in clinica
    • Tempo di recupero o di un’interruzione della Parte 1 e accesso alla Parte 2 a causa di un marcato deterioramento della funzione. Il recupero avviene se vi è un peggioramento rispetto al Basale nel punteggio ALSFRS-R >10 punti o un declino della Capacità Vitale Lenta (CVL) <40% del valore previsto al Giorno 141 dello studio, o successivamente, che viene confermato dopo un intervallo di 4 settimane. Per recupero si intende che il/la paziente può interrompere la Parte 1 e accedere alla Parte 2 dello studio
    • Sopravvivenza libera da ventilazione assistita (VAFS), definita come il tempo alla prima occorrenza di 1 dei seguenti eventi:
    o Decesso
    o Ventilazione permanente (>22 ore di ventilazione meccanica [invasiva o non invasiva] al giorno per >21 giorni consecutivi in assenza di un evento acuto reversibile)
    E.5.1.1Timepoint(s) of evaluation of this end point
    From Baseline to Study Day 225 in Part 1 Cohort A
    Variazione dal Basale al Giorno 225 dello studio nella Coorte A della Parte 1
    E.5.2Secondary end point(s)
    Evaluate the effects of ION363 vs. placebo on change from Baseline to Study Day 225 in Part 1 Cohort A on clinical assessments and biomarkers of disease severity. Specifically, on the following endpoints:
    • Change from Baseline in Amyotrophic Lateral Sclerosis Specific Quality of Life – Revised (ALSSQOL-R)
    • Change from Baseline in in-clinic Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
    • Survival
    • Change from Baseline in in-clinic Slow Vital Capacity (SVC)
    • Change from Baseline in Handheld Dynamometry (HHD)
    • Change from Baseline in Neurofilament light (NfL) concentration in CSF
    • Change from Baseline in FUS protein concentration in CSF
    Valutare gli effetti di ION363 rispetto al placebo sulla variazione dal basale al Giorno 225 dello studio nella Coorte A della Parte 1 sulle valutazioni cliniche e sui biomarcatori della gravità della malattia. Nello specifico, sui seguenti endpoint:
    • Variazione rispetto al Basale nella qualità della vita specifica per la sclerosi laterale amiotrofica – rivista (ALSSQOL-R)
    • Variazione rispetto al Basale nella Scala di valutazione funzionale della sclerosi laterale amiotrofica-rivista (ALSFRS-R) in clinica
    • Sopravvivenza
    • Variazione rispetto al Basale nella Capacità Vitale Lenta (CVL) in clinica
    • Variazione rispetto al Basale nella dinamometria manuale (HHD)
    • Variazione rispetto al Basale nella concentrazione di neurofilamento a catena leggera (NfL) nell’LCS
    • Variazione rispetto al Basale nella concentrazione della proteina FUS nell’LCS
    E.5.2.1Timepoint(s) of evaluation of this end point
    From Baseline to Study Day 225 in Part 1
    Variazione dal Basale al Giorno 225 dello studio nella Parte 1
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    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 No
    E.8.1.6Cross over Yes
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Parte 1 in doppio cieco e Parte 2 in aperto
    Part 1 double blind and Part 2 open label
    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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA8
    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
    Japan
    Korea, Republic of
    Turkey
    United States
    Belgium
    France
    Germany
    Italy
    United Kingdom
    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
    LVLS
    LVLS, ultima visita dell'ultimo soggetto
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months5
    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 Yes
    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) Yes
    F.1.1.6.1Number of subjects for this age range: 12
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 50
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 2
    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 No
    F.4 Planned number of subjects to be included
    F.4.1In the member state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 27
    F.4.2.2In the whole clinical trial 64
    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)
    It is the intent of the Sponsor to continue providing access to treatment through the Open label Extension Period until marketing authorization.
    E' intenzione dello Sponsor continuare a fornire l' accesso al trattamento durante il periodo di estensione in aperto fino all' immissione in commercio
    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 Decision2022-02-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-09-26
    P. End of Trial
    P.End of Trial StatusOngoing
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