Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44154   clinical trials with a EudraCT protocol, of which   7326   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2016-002399-28
    Sponsor's Protocol Code Number:RAP-ALS
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-01-23
    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 number2016-002399-28
    A.3Full title of the trial
    Rapamycin (Sirolimus) treatment for amyotrophic lateral sclerosis
    Rapamycin (Sirolimus) treatment for amyotrophic lateral sclerosis
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Rapamycin (Sirolimus) treatment for amyotrophic lateral sclerosis
    Rapamycin (Sirolimus) treatment for amyotrophic lateral sclerosis
    A.3.2Name or abbreviated title of the trial where available
    RAP.ALS
    RAP-ALS
    A.4.1Sponsor's protocol code numberRAP-ALS
    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 SponsorAZIENDA OSPEDALIERO-UNIVERSITARIA POLICLINICO DI MODENA
    B.1.3.4CountryItaly
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportArisla
    B.4.2CountryItaly
    B.4.1Name of organisation providing supportPfizer
    B.4.2CountryItaly
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNuovo Ospedale Civile S. Agostino Estense
    B.5.2Functional name of contact pointCoordinating Site
    B.5.3 Address:
    B.5.3.1Street AddressVia P. Giardini 1355
    B.5.3.2Town/ cityModena
    B.5.3.3Post code41126
    B.5.3.4CountryItaly
    B.5.4Telephone number0593961640
    B.5.5Fax number0593963775
    B.5.6E-mailj.mandrioli@ausl.mo.it
    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 Yes
    D.2.1.1.1Trade name RAPAMUNE - 1 MG 100 COMPRESSE RIVESTITE IN BLISTER USO ORALE
    D.2.1.1.2Name of the Marketing Authorisation holderPFIZER LIMITED
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameRapamune
    D.3.4Pharmaceutical form Coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    definite or probable ALS
    SLA definita o probabile
    E.1.1.1Medical condition in easily understood language
    definite or probable ALS
    SLA definita o probabile
    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 20.0
    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 assess whether Rapamycin administration increases Tregs number in treated patients compared to control arm
    Valutare se Rapamicina determina un aumento dei linfociti Treg in pazienti affetti da SLA rispetto al braccio di controllo
    E.2.2Secondary objectives of the trial
    To assess safety and tolerability of Rapamycin in ALS patients; to assess the minimum dosage to have RAPAMYCIN in CSF; to assess changes in immunological (activation and homing of T,B,NK cell subpopulations) and inflammatory markers, and on mTOR downstream pathway (S6RP phosphorylation); to assess clinical activity (ALSFRS-R, survival, FVC) and effect on quality of life (ALSAQ40). To assess if and at what dosage Rapamycin passes through blood brain barrier (BBB).
    Valutare sicurezza e tollerabilità di Rapamicina in pazienti con SLA; valutare eventuali cambiamenti a livello di marcatori biologici del sistema immunitario (attivazione e homing dei linfociti T, B e NK), di infiammazione e a livello della cascata di segnali correlata alla proteina mTOR (fosforilazione di S6RP); valutare l’effIicacia clinica (tramite ALSFRS-R, sopravvivenza e FVC) di Rapamicina rispetto al placebo e l’effetto sulla qualità della vita (mediante ALSAQ40); valutare se e a che dosaggio Rapamicina attraversa la barriera ematoencefalica.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Patient diagnosed with a laboratory supported , clinically “probable” or “definite” amyotrophic lateral sclerosis according to the Revised El Escorial criteria (Brooks, 2000)
    - Familial or sporadic ALS
    - Female or male patients aged between 18 and 75 years old
    - Disease duration from symptoms onset no longer than 18 months at the screening visit
    - Patient treated with a stable dose of Riluzole (100 mg/day) for at least 30 days prior to screening
    - Patients with a weight > 50 kg and a BMI ≥18
    - Patient with a FVC ≥ 70 % predicted normal value for gender, height, and age at the screening visit
    - Patient able and willing to comply with study procedures as per protocol
    - Patient able to understand, and capable of providing informed consent at screening visit prior to any protocol-specific procedures
    - Use of effective contraception both for males and females
    - Pazienti con diagnosi di SLA definita, clinicamente probabile o probabile con supporto di laboratorio secondo i criteri di El Escorial – Revised
    - SLA familiare o sporadica
    - Età: 18-75 anni
    - Esordio di malattia ≤18 mesi dalla visita di screening
    - Pazienti in trattamento stabile con Riluzolo (100 mg/day) da almeno 30 giorni al momento dello screening
    - FVC ≥ 70% al momento dello screening
    - Peso > 50 Kg e BMI ≥ 18 al momento dello screening
    - Capacità di comprendere e aderire a quanto richiesto dal protocollo dello studio
    - Capacità di fornire il Consenso Informato
    - Utilizzo di metodi contraccettivi (donne e uomini in età fertile)
    E.4Principal exclusion criteria
    - Prior use of Sirolimus
    - Prior allergy/sensitivity to Sirolimus or macrolides
    - Any medical disorder that would make immunosuppression contraindicated, including but not limited to, acute infections requiring antibiotics, patients with known diagnosis of HIV, TBC, hepatitis B or C infection or history of malignancy
    - Severe comorbidities (heart, renal, liver failure), autoimmune diseases or any type of interstitial lung disease
    - White blood cells<4,000/mm³, platelets count<100,000/mm³, hematocrit<30%
    - Patient who underwent non invasive ventilation, tracheotomy and /or gastrostomy
    - Women who are pregnant or breastfeeding
    - Participation in pharmacological studies within the last 30 days before screening
    - Patients with known SOD1 mutation
    - Pregresso uso di Sirolimus
    - Pregressa allergia o ipersensibilità al Sirolimus (Rapamicina) o ai macrolidi
    - Qualsiasi condizione clinica controindicante un trattamento immunosoppressivo, incluso ma non limitato a infezioni acute richiedenti terapia antibiotica, HIV, TBC, epatite B o C, storia clinica di neoplasia.
    - Comorbilità severe (insufficienza cardiaca, renale, epatica), malattie autoimmuni, patologie respiratorie interstiziali.
    - Conta leucocitaria < 4.000/mm³, Piastrinopenia < 100.000/mm³, Ematocrito < 30%
    - Presenza di PEG o Ventilazione Non Invasiva
    - Gravidanza o allattamento
    - Partecipazione a qualsiasi trial farmacologico nei 30 giorni precedenti lo screening
    - Pazienti portatori noti di mutazione SOD1
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of patients exhibiting a positive response (considered as increase in Treg of at least 30%), comparing baseline and treatment end (WEEK 18) between Rapamycin and placebo arm, using mAbs anti-CD3,-4,-25,-127,-FoxP3 plus activation (HLA-DR,CD38) and homing (CXCR3) markers and flow cytometry (FCM)
    Proporzione di pazienti caratterizzati da una risposta positiva al trattamento (definita come un incremento dei Treg > 30% in almeno il 50% dei trattati rispetto ad un massimo del 5% dei controlli, comparando i valori al baseline e alla settimana 18), tra il gruppo di pazienti trattato con R e quello trattato con placebo, utilizzando anticorpi monoclonali anti-CD3,-4,-25,-127,-FoxP3 e marcatori di attivazione (HLA-DR, CD38) e homing (CXCR3) linfocitario e tecniche di citometria a flusso.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 18
    18 settimane
    E.5.2Secondary end point(s)
    1. Measuring Rapamycin level in CSF
    2. Quantifying the phosphorylation of the S6 ribosomal protein (S6RP) between Rapamycin arm and placebo arm
    3. Measure changes in different biomarkers (creatinin e albumin, CK, vitamin D, neurofilament) between Rapamycin arm and placebo arm
    4. Molecular analysis of the inflammasome system between Rapamycin arm and placebo arm
    5. Amyotrophic Lateral Sclerosis functional rationg scale (ALSFRS)
    6. Overall survival
    7. Survival rate
    8. Forced vital capacity (FVC) score
    1. Misurazione dei livelli di Rapamicina nel fluido cerebrospinale
    2. Quantificazione della fosforilazione della proteina ribosomale S6 (S&RP) tra il braccio con Rapamicina e il braccio con placebo
    3. Misurazione delle variazioni in differenti biomarkers (creatinina, albumina, CK, vitamina D, neurofilamenti) tra il braccio con Rapamicina e il braccio con placebo
    4. Analisi molecolare del complesso dell’inflammasoma tra il braccio con Rapamicina e il braccio con placebo
    5. Scala Valutazione Funzionale SLA (ALSFRS)
    6. Sopravvivenza globale
    7. Tasso di sopravvivenza
    8. Punteggio della capacità vitale forzata (FVC)
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Week 18
    2. Baseline, week 8, 18 (treatment end), 30 and 54
    3. Baseline, week 8, 18 (treatment end), 30 and 54
    4. Baseline, week 8, 18 (treatment end), 30 and 54
    5. Baseline, week 4, 8, 12, 18, 30, 42 e 54
    6. From randomization to date of Death or tracheostomy
    7. Week 18, 30, 42 and 54
    8. Week 4, 8, 12, 18, 30, 42, 54
    1. Settimana 18
    2. Baseline, settimana 8, 18 (fine trattamento), 30 e 54
    3. Baseline, settimana 8, 18 (fine trattamento), 30 e 54
    4. Baseline, settimana 8, 18 (fine trattamento), 30 e 54
    5. Baseline, settimana 4, 8, 12, 18, 30, 42 e 54
    6. Dalla randomizzazione alla data del decesso o tracheostomia
    7. Settimana 18, 30, 42 e 54
    8. Settimana 4, 8, 12, 18, 30, 42, 54
    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 No
    E.6.7Pharmacodynamic No
    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) 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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 concerned8
    E.8.5The trial involves multiple Member States No
    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 No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    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 years2
    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.1.1Number of subjects for this age range: 1
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 45
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 18
    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 Yes
    F.3.3.2Women of child-bearing potential using contraception No
    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 state63
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 63
    F.4.2.2In the whole clinical trial 63
    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)
    Patients will be treated according to the local clinical practice of the site
    I pazienti saranno trattati in accordo alla pratica clinica locale del centro
    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 Decision2017-07-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-05-09
    P. End of Trial
    P.End of Trial StatusCompleted
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA