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    Summary
    EudraCT Number:2018-003385-14
    Sponsor's Protocol Code Number:AROAAT2001
    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:2021-01-19
    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 number2018-003385-14
    A.3Full title of the trial
    A Placebo-Controlled, Multi-dose, Phase 2/3 Study to Determine the Safety, Tolerability and Effect on Liver Histologic Parameters in Response to ARO-AAT in Patients with Alpha-1 Antitrypsin Deficiency (AATD)
    Studio di fase2/3, controllato con placebo, multidose, della sicurezza, della tollerabilità e degli effetti sui parametri istologici epatici in risposta a ARO-AAT in pazienti con deficienza di alpha-1 antitripsina (AATD).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Placebo-Controlled, Multi-dose, Phase 2/3 Study to Determine the Safety, Tolerability and Effect on Liver Histologic Parameters in Response to ARO-AAT in Patients with Alpha-1 Antitrypsin Deficiency (AATD).
    Studio di fase2/3, controllato con placebo, multidose, della sicurezza, della tollerabilità e degli effetti sui parametri istologici epatici in risposta a ARO-AAT in pazienti con deficienza di alpha-1 antitripsina (AATD).
    A.3.2Name or abbreviated title of the trial where available
    AROAAT2001
    AROAAT2001
    A.4.1Sponsor's protocol code numberAROAAT2001
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03945292
    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 SponsorARROWHEAD PHARMACEUTICALS
    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 supportArrowhead Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationArrowhead Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointMei Ling Chang-Lok
    B.5.3 Address:
    B.5.3.1Street Address225 South Lake Ave., Suite 1050
    B.5.3.2Town/ cityPasadena
    B.5.3.3Post code91101
    B.5.3.4CountryUnited States
    B.5.4Telephone number0016263043400
    B.5.5Fax number0016263043401
    B.5.6E-mailmchanglok@arrowheadpharma.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 Yes
    D.2.5.1Orphan drug designation numberEU/3/18/2048
    D.3 Description of the IMP
    D.3.1Product nameARO-AAT Injection
    D.3.2Product code [ARO-AAT]
    D.3.4Pharmaceutical form Powder and solvent for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 2175009-08-0
    D.3.9.2Current sponsor codeADS-001
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number230
    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 typeAPI (ADS-001) contained in ARO-AAT is a synthetic, double-stranded, hepatocyte targeted N-acetyl galactosamine (NAG)-conjugated RNAi trigger
    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 placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Alpha-1 antitrypsin deficiency (AATD)-associated liver disease.
    Malattia epatica associata ad una deficienza di alfa-1 antitripsina.
    E.1.1.1Medical condition in easily understood language
    Alpha-1 antitrypsin deficiency (AATD)-associated liver disease.
    Malattia epatica associata ad una deficienza di alfa-1 antitripsina.
    E.1.1.2Therapeutic area Diseases [C] - Digestive System Diseases [C06]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.1
    E.1.2Level LLT
    E.1.2Classification code 10001806
    E.1.2Term Alpha-1 anti-trypsin deficiency
    E.1.2System Organ Class 100000004850
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Part A:
    • To select a single dose level for use in Part B of the study based on a combined evaluation of safety and pharmacodynamic dose response in each Part A cohort using change from baseline in soluble liver Z-AAT, insoluble liver Z-AAT and serum AAT levels.
    Part B:
    • To evaluate efficacy (as assessed by the proportion of ARO-AAT treated patients relative to placebo achieving a 2-point improvement in a histologic grading scale of alpha-1 antitrypsin deficiency associated liver disease AND no worsening of liver fibrosis based on Ishak score on end of study biopsy).
    Parte A:
    • Selezionare un singolo livello di dose da utilizzare nella Parte B sulla base di una valutazione integrata di sicurezza e di dose-risposta farmacodinamica in ciascuna coorte della Parte A, utilizzando le modifiche rispetto alla "baseline" di Z-AAT epatica solubile, Z-AAT epatica insolubile e delle concentrazioni sieriche di AAT.
    Parte B:
    • Valutare l'efficacia (quatificata in base alla proporzione di pazienti trattati con ARO-AAT rispetto a quelli trattati con placebo che raggiungono un miglioramenti di 2-punti nel "grading" istologico dell'epatopatia associata a deficienza di alfa-1 antitripsina associata, in assenza di un peggioramento della fibrosi epatica basata sul punteggio Ishak alla biopsia di fine studio).
    E.2.2Secondary objectives of the trial
    Part B:
    • To evaluate change from baseline on a histologic grading scale of alpha-1 antitrypsin deficiency associated liver disease on end of study biopsy in ARO-AAT treated patients relative to placebo.
    • To evaluate the proportion of ARO-AAT treated patients with Ishak fibrosis stage 1 or greater relative to placebo achieving at least a 1-stage improvement in fibrosis on end of study biopsy based on Ishak fibrosis score.
    • To evaluate change from baseline in Ishak fibrosis score at end of study biopsy in ARO-AAT treated patients relative to placebo.
    Parte B:
    • Valutare le modifiche rispetto alla "baseline" nel "grading" istologico della epatopatia associata a deficienza di alfa-1 antitripsina alla biopsia di fine studio nei pazienti trattati con ARO-AAT rispetto a quelli trattati con placebo;
    • Valutare la proporzione di pazienti con fibrosi di Ishak fibrosis stadio 1 o superiore trattati con ARO-AAT rispetto a quelli trattati con placebo, che raggiungono un miglioramento di almeno 1 grado nella fibrosi nella biopsia di fine studio nel punteggio fibrotico;
    • Valutare le modifiche rispetto alla "baseline" nel punteggio fibrotico di Ishak alla biopsia di fine studio nel pazienti trattati con ARO-AAT rispetto a quelli trattati con placebo.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or non-nursing female patients 18-75 years of age, inclusive, at the time of Screening with previous diagnosis of PiZZ genotype Alpha-1 Antitrypsin Deficiency. PiZZ diagnosis from source verifiable medical records is permitted. Otherwise, patients must undergo PiZZ confirmatory testing at Screening. PiMZ or PiSZ genotypes are not permitted.
    2. Able and willing to provide written informed consent prior to the performance of any study specific procedures.
    3. Liver biopsy as part of the AROAAT2001 study at Screening indicating Metavir F2 or F3 (or equivalent on other grading scales) liver fibrosis based on local pathologist read.
    4. A 12-lead ECG at Screening that, in the opinion of the Investigator, has no new acute abnormalities (e.g. new onset atrial fibrillation) that compromise participant's safety in this study. Stable disease (e.g. stable atrial fibrillation) is acceptable.
    5. Non-smoker (defined as does not smoke cigarettes daily for at least 12 months) with current non-smoking status confirmed by urine cotinine at screening AND any previous smoking history prior to 12 months must be < 15 pack years. Patients may be on nicotine replacement (patch or gum). e-cigarettes (vapor) is not permitted. A positive urine cotinine result due to nicotine replacement is acceptable for enrollment at the discretion of the Investigator.
    6. Participants using highly effective contraception during the study and for 3 months following the last dose of ARO-AAT. Males must not donate sperm for at least 3 months post last dose of study treatment. Females of childbearing potential must have a negative urine pregnancy test at Screening and on Day 1 pre-dose. Females not of childbearing potential must be post-menopausal (defined as cessation of regular menstrual periods for at least 12 months), confirmed by follicle-stimulating hormone (FSH) consistent with post-menopausal state based on lab reference ranges.
    1. Pazienti maschio o femmine non in allattamento di età 18-75 anni compresi al momento dello Screening con precedente diagnosi di deficienza di alfa-1 antitripsina genotipo PiZZ. E' ammessa la diagnosi di PiZZ sulla base di referti medici verificabili; in caso contrario, i pazienti devono sottoporsi ad un test confirmativo di PiZZ allo Screening. I genotipi PiMZ e PiSZ genotypes non sono consentiti.
    2. Capace di manifestare il proprio consenso informato scritto prima dell'esecuzione di qualsiasi attività specifica dello studio.
    3. Biopsia epatica come parte dello studio AROAAT2001 allo Screening che mostri una fibrosi epatica Metavir F2 or F3 (o altra scala di gradazione identica) sulla base della lettura del patologo locale.
    4. ECG a 12-derivazioni allo Screening che, nell'opinione dello Sperimentatore, non mostri alcuna anomalia acuta (p.e., una fibrillazione atrial di recente insorgenza) che comprometta la sicurezza del paziente nello studio. Una patologia cronica (p.e., una fibrillazione atriale stabile) è accettabile.
    5. Non fumatore (ovvero, un soggetto che non fuma sigarette quotidianamente da almeno 12 mesi) con uno stato di non-fumatore confermato dalla ricerca di nicotina urinaria allo Screening E una storia di fumo precedente igli ultimi 12 mesi con meno di 15 pacchetti di sigarette / anno. I pazienti possono essere in trattamento con nicotina (cerotti o gomme). Le sigarette elettroniche (vapore) non sono consentite. Il risultato positivo per la cotinina urinaria dovuto alla somministrazione di nicotina è accettabile per l'arruolamento a discrezione dello Sperimentatore.
    6. Pazienti che fanno uso di un metodo contraccettivo altamente efficace per l'intera durata dello studio e per i tre mesi successivi all'ultima dose di ARO-AAT. I maschi non devono fare donazione di sperma per almeno 3 mesi dopo l'ultima dose del farmaco in studio. Le femmine in età fertile devono avere un test di gravidanza negativo allo Screening ed al Giorno 1 prima del trattamento. Le femmine non in età fertile devono essere in menopausa (definita come la cessazione del flusso mestruale periodico da almeno 12 mesi), confermata fa un valore di ormone follicolo-stimolante (FSH) in linea con la condizione post-menopausale sulla base di valori di riferimento del laboratorio.
    E.4Principal exclusion criteria
    1. INR > 1.2 at Screening (one retest permitted). If based on opinion of Investigator and/or prescribing physician patient is appropriate for anticoagulant holiday, patient may stop taking anticoagulant for an appropriate washout period and if indicated a repeat INR within < 1.2 would be acceptable. Vitamin K may be used for reversal. If INR is not indicated (direct thrombin inhibitors or Xa inhibitors) then appropriate washout period alone may be acceptable.
    2. Platelet count < 150 x 109/L at Screening
    3. ALT and AST levels > 250 U/L at Screening
    4. eGFR < 60mL/min at Screening
    5. FEV1 <65% of predicted at Screening
    6. Recent (last 3 months) pneumonia or lower respiratory infection. Patient reported infection is not sufficient to meet this criterion.
    7. Unavoidable exposure to inhaled environmental toxins that in the clinical judgement of the investigator could impair pulmonary function significantly over the course of the study.
    8. Human immunodeficiency virus infection, as shown by the presence of anti-HIV antibody (sero-positive)
    9. Seropositive for HBV or HCV. Cured HCV (positive antibody test without detectable HCV RNA is acceptable).
    10. Uncontrolled hypertension.
    11. A history of torsades de pointes, ventricular rhythm disturbances (e.g., ventricular tachycardia or fibrillation), untreated heart block (excluding first-degree block, being PR interval prolongation only), congenital long QT syndrome or new acute ST segment elevation or depression or new acute Q wave on ECG. Stable atrial dysrhythmias (e.g. stable atrial fibrillation) are acceptable.
    12. Symptomatic heart failure (per NYHA guidelines), unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction < 20%, transient ischemic attack (TIA) or cerebrovascular accident (CVA) within 6 months prior to Screening
    13. History of malignancy within the last 1 year except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer.
    14. History of major surgery within the prior 1 month prior to Screening
    15. Regular use of alcohol within one month prior to the Screening visit
    16. Use of illicit drugs within 1 year prior to the Screening visit or positive urine drug screen at Screening.
    17. Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study involving a therapeutic intervention.
    18. Blood donation (=500 mL) within 7 days prior to study treatment administration.
    19. Any concomitant medical or psychiatric condition or social situation that would make it difficult to comply with protocol requirements or put the participant at additional safety risk. Patients with NASH, NAFLD, metabolic syndrome, well controlled diabetes mellitus (even if on insulin) or hemochromatosis are acceptable if disease is stable and does not pose a significant threat to subject participation.
    20. A history of thromboembolic disease, myocardial infarction, stroke within three (3) months of screening.
    21. Any other condition or finding of clinical relevance at Screening, that in the opinion of the Investigator would render the participant unsuitable for enrollment or could interfere with participating in and completing the study.
    22. Previous diagnosis of definitive liver cirrhosis based on biopsy or complications of cirrhosis based on source verifiable medical record.
    23. Patients who have undergone lung or liver transplant for AATD are excluded.
    24. Diagnosis of F4 (Metavir) or similar grading scale equivalent indicating definitive cirrhosis on pre-dose liver biopsy completed as part of the AROAAT2001 study based on local pathologist read or based on historical liver biopsy (last 6 months from consent) with a source verifiable pathologist read of definitive liver cirrhosis.
    25. A Screening liver biopsy fibrosis score of < Metavir F2 (or similar histologic grading scale equivalent) based on local read is exclusionary
    1. Valore di INR > 1.2 allo Screening (è consentito il retest). Se - sulla base dell'opinione dello Sperimentatore e/o del medico prescritore - il paziente può sospendere il trattamento anticoagulante, il paziente può interrompere l'assunzione di anticoagulanti per un periodo appropriato di "washout" e, se indicato, un valore al retest < 1.2 può essere accettabile. La vitamina K può essere utilizzata per eliminare l'attività anticoagulante. Se l'INR non è indicato (inibitori diretti della trombina o inibitori del fattore Xa), allora un periodo appropriato di "washout" può essere da solo accettabile;
    2. Conta piastrinica < 150 x 109/L allo Screening;
    3. Livelli di ALT e AST > 250 U/L allo Screening;
    4. eGFR < 60mL/min allo Screening;
    5. FEV1 < 65% del valore previsto allo Screening;
    6. Polmonite recente (ultimi 3 mesi) o infezione delle basse vie respiratorie. Un'infezione riferita dai pazienti non è sufficiente per rientrare nel criterio;
    7. Esposizione non evitabile a tossine ambientali inalate che - nel giudizio clinico dello Sperimentatore - possano alterare la funzionalità polmonare in maniera significativa nel corso dello studio;
    8. Infezione HIV, se dimostrata dalla presenza di anticorpi anti-HIV (sieropositività);
    9. Sieropositività per HBV o HCV. L'HCV curata (positività agli anticorpi in assenza di HCV RNA misurabile) è accettabile;
    10. Ipertensione non controllata;
    11. Storia di "torsades de pointes", disturbi del ritmo ventricolare (o.e., tachicardia ventricolare o fibrillazione), blocco non trattato (escluso blocchi di primo grado con solo PR prolungato), sindrome congenita del QT lungo o elevazione del segmento ST acuto o depressione or nuova onda Q acuta. Le aritmie atriali stabili (p.e., stable fibrillazione atrial stabile) sono accettabili;
    12. Scompenso cardiaco sintomatico, angina instabile, infarto miocardico, malattia cardiovascolare grave (frazione eiezione < 20%, TIA o ictus cerebrovasculare nei 6 mesi precedenti lo Screening;
    13. Storia di tumori nell'anno precedente, ad eccezione del carcinoma basocellulare, del carcinoma squamocelluare, dei tumori superficiali della vescica, e del cercinoma cervicale in situ;
    14. Storia di chiurugie maggiori nel mese precedente lo Screening;
    15. Uso regolare di alcohol nel mese precedente lo Screening;
    16. Uso di droghe illegali nell'anno precente lo Screening o screening urinario di droghe positivo allo Screening;
    17. Uso di farmaci o dispositivi sperimentali nei 30 giorni prima dell'inizio del trattamento o partecipazione in atto ad uno studio sperimentale con intervento terapeutico;
    18. Donazione di sangue (=500 mL) nei 7 giorni precedenti la somministrazione del farmaco in studio;
    19. Ogni condizione medica o psichiatrica concomitante o situazione sociale che renda difficile l'adesione alle richieste del protocollo o metta il soggetto a rischio;
    20. Storia di malattia tromboembolica, infarto miocardico, stroke nei tre (3) mesi precedenti lo Screening;
    21. Ogni altra condizione o evidenza clinica allo Screening che - a giudizio dello Sperimentatore - renda il paziente inadeguato all'arruolamento o possa interferire con la partecipazione ed il completamento dello studio;
    22. Precedente diagnosi di cirrosi epatica confermata da biopsia o complicazioni di cirrosi confermate dalla cartella clinica del paziente;
    23. Pazienti che siano stati sottoposti a trapianto di fegato o di polmone per AATD sono esclusi;
    24. Diagnosi di F4 (Metavir) o grado simile equivalente, indicativo di cirrosi epatica confermata dalla biopsia epatica predose come parte dello studio AROAAT2001, dal referto del patologo o da una biopsia epatica storica (negli ultimi 6 mesi prima del consenso) con referto di patologo verificabile;
    25. Fibrosi epatica allo Screening di grado < Metavir F2 (o grado istologico simile equiavlente) confermato da refero locale.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint of Part B of the study is the proportion of ARO-AAT treated patients relative to placebo who achieve a 2-point improvement in a histologic grading scale of alpha-1 antitrypsin associated liver disease AND no worsening of liver fibrosis based on Ishak fibrosis score on end of study biopsy.
    L'endpoint di efficacia primaria nella Parte B è la percentuale di pazienti trattati con ARO-AAT rispetto a quelli trattati con placebo che raggiungono un miglioramento di 2-punti nel "grading" istologico della epatopatia associata a deficienza di alfa-1 antitripsina, in assenza di un peggioramento della fibrosi epatica sulla base del punteggio di Ishak alla biopsia di fine studio.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Part A: Days 1, 29, 113, and every 84 days thereafter until a single dose level is selected
    Part B: Days 1, 29, 113 then every 84 days (Days 197, 281, 365, 449, 533, 617)
    Parte A: Giorni 1, 29, 113, ed ogni 84 successivi fino a selezione di un singolo livello di dosaggio.
    Part B: Giorni 1, 29, 113 e successivamente ogni 84 giorni (Giorni 197, 281, 365, 449, 533, 617).
    E.5.2Secondary end point(s)
    Part B secondary endpoints include:
    1) Change from baseline on a histologic grading scale of AATD-associated liver disease on end of study biopsy in ARO-AAT treated patients relative to placebo,
    2) Proportion of ARO-AAT treated patients with Ishak fibrosis stage-1 or greater fibrosis relative to placebo achieving at least a 1-stage improvement in fibrosis on end of study biopsy based on Ishak fibrosis score;
    3) Change from baseline in Ishak fibrosis score at end of study biopsy in ARO-AAT treated patients relative to placebo.
    Gli endpoint secondari della Parte B comprendono:
    1) Modifiche rispetto alla "baseline" del "grading" istologico della epatopatia associata ad AATD alla biopsia di fine studio nei pazienti trattati con ARO-AAT rispetto a quelli trattati con placebo;
    2) Proporzione dei pazienti con fibrosi grado 1 Ishak trattati con ARO-AAT rispetto a quelli trattati con placebo che raggiungono un miglioramento della fibrosi di almeno 1 stadio alla biopsia di fine studio sulla base del punteggio fibrotico di Ishak;
    3) Modifiche rispetto alla "baseline" del punteggio fibrotico di Ishak alla biopsia di fine studio nei pazienti trattati con ARO-AAT rispetto ai pazienti trattati con placebo.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Part B: Days 1, 29, 113 then every 84 days (Days 197, 281, 365, 449, 533, 617)
    Parte B: Giorni 1, 29, 113 e successivamente ogni 84 giorni (Giorni 197, 281, 365, 449, 533, 617),
    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 Yes
    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 Yes
    E.8.1.7.1Other trial design description
    Phase 2 to Phase 3 adaptive design
    Phase 2 to Phase 3 adaptive design
    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 trial1
    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 EEA15
    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
    Ireland
    Italy
    Netherlands
    Poland
    Portugal
    Spain
    Sweden
    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
    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 months10
    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 months10
    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: 110
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 8
    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 state4
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 40
    F.4.2.2In the whole clinical trial 118
    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)
    There will be a follow-up telephone call to assess for pregnancy
    occurrence 90 days post last dose.
    There will be a follow-up telephone call to assess for pregnancy
    occurrence 90 days post last dose.
    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 Decision2019-09-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-07-03
    P. End of Trial
    P.End of Trial StatusOngoing
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