E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rheumatoid arthritis |
Artrite Reumatoide |
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E.1.1.1 | Medical condition in easily understood language |
RA, Rheumatoid arthritis, autoimmune disease that causes chronic joint inflammation |
AR, Artrite Reumatoide, malattia autoimmune che causa infiammazione cronica alle giunture |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10028395 |
E.1.2 | Term | Musculoskeletal and connective tissue disorders |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the clinical efficacy of NNC0109-0012 compared to placebo when administered as weekly repeat s.c. injections in patients with active rheumatoid arthritis (RA) with inadequate responses to methotrexate (MTX) while on a stable background of MTX therapy. |
Indagare l’efficacia clinica di NNC0109-0012, rispetto al placebo, quando somministrato come iniezioni sottocutanee (s.c.) ripetute, settimanali, in pazienti affetti da artrite reumatoide (AR) acuta, con risposte inadeguate a metotressato (MTX) e che sono su terapia stabile con MTX. |
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E.2.2 | Secondary objectives of the trial |
- To investigate the effects of NNC0109-0012 compared to placebo on additional clinical outcomes measuring disease activity - To investigate the effects of NNC0109-0012 compared to placebo on Patient Reported Outcomes (PROs) - To investigate the effects of NNC0109-0012 compared to placebo on biomarkers assessing disease activity, MoA, structural damage in addition to total IL-20 and biomarkers predictive of response - To describe safety and tolerability of NNC0109-0012 - To describe the trough concentration of NNC0109-0012 at steady state - To describe the potential immunogenicity of NNC0109-0012 - To explore the dose response relationship for NNC0109-0012 on clinical efficacy outcomes - To investigate the effect of NNC0109-0012 compared to placebo on health care resource utilisation |
- Indagare gli effetti di NNC0109-0012, rispetto al placebo, su esiti clinici aggiuntivi, che misurano l’attività della malattia - Indagare gli effetti di NNC0109-0012, rispetto al placebo, sugli esiti riferiti dai pazienti (Patient Reported Outcomes, PRO) - Indagare gli effetti di NNC0109-0012, rispetto al placebo, sui biomarcatori che valutano l’attività della malattia, gli anticorpi monoclonali, il danno strutturale oltre all’IL-20 totale e ai biomarcatori predittivi della risposta - Descrivere la sicurezza e la tollerabilità di NNC0109-0012 - Descrivere la concentrazione minima di NNC0109-0012 in regime stazionario - Descrivere l’immunogenicità potenziale di NNC0109-0012 - Esplorare la relazione dose-risposta di NNC0109-0012 sugli esiti di efficacia clinica - Indagare gli effetti di NNC0109-0012, rispetto al placebo, sull’utilizzo delle risorse sanitarie |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
PHARMACOGENETIC:
Vers:4.0
Date:2012/05/11
Title:A randomised, double blind, placebo-controlled, multiple dose, phase 2b, 24 week trial followed by an open label extension of NNC0109-0012, an anti-IL-20 biologic, in patients with active rheumatoid arthritis who are inadequate responders to Methotrexate
Objectives:The purpose of this part of the trial is to investigate why people react differently to medications.
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FARMACOGENETICA:
Vers:4.0
Data:2012/05/11
Titolo:Sperimentazione di fase 2b, randomizzata, in doppio cieco, controllata con placebo, a dose multipla, di 24 settimane, seguita da un’estensione in aperto con NNC0109-0012, un biologico anti-IL-20, in pazienti affetti da artrite reumatoide attiva che sono rispondenti inadeguati a Metotressato
Obiettivi:Lo scopo di questa parte della sperimentazione è di scoprire come mai alcune persone hanno reazioni diverse ai farmaci.
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E.3 | Principal inclusion criteria |
1. Informed consent must be obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial 2. Age between 18 and 75 years (both years inclusive) 3. A documented diagnosis of RA at least 6 months prior to screening visit, according to the American College of Rheumatology (EULAR/ACR 2010 criteria) or by standard criteria (ACR 1987) if diagnosis was made earlier than 2010. 4. Active RA, characterised by: a. > 5 tender and > 5 swollen joints based on a 28 joint count b. CRP ≥ 1.0 mg/dL (10 mg/L) 5. Patients can be on methotrexate with or without hydroxychloroquine/chloroquine a. Methotrexate treatment (≥ 15.0 mg/week) for at least 16 weeks, (≥ 15.0 mg/week to ≤ 25 mg/week) for at least 8 weeks prior to screening. Patient can be on MTX as low as 10 mg/week only if due to MTX intolerance b. Hydroxychloroquine (200-400 mg/day p.o.) or chloroquine (250- 500 mg/day p.o.) treatment for at least 8 weeks prior to screening visit |
1. Il consenso informato deve essere ottenuto prima di una qualsiasi attività legata alla sperimentazione. Le attività legate alla sperimentazione corrispondono a una qualsiasi procedura effettuata come parte della sperimentazione, incluse le attività per determinare l’idoneità alla sperimentazione 2. Età compresa tra 18 e 75 anni (inclusi) 3. Una diagnosi documentata di AR, almeno 6 mesi prima della visita di screening, che soddisfi i criteri EULAR/ACR (American College of Rheumatology) del 2010 o i criteri standard (ACR 1987), se la diagnosi è stata effettuata prima del 2010. 4. AR attiva, caratterizzata da: a. > 5 articolazioni gonfie e > 5 articolazioni dolenti in base al conteggio su 28 articolazioni b. CRP 1,0 mg/dl (10 mg/l) 5. I pazienti possono essere trattati con metotressato con o senza idrossiclorochina/clorochina a. Trattamento con metotressato (≥ 15,0 mg/settimana) per almeno 16 settimane, (da ≥ 15,0 mg/settimana a ≤ 25 mg/settimana) per almeno 8 settimane prima dello screening. Il paziente può assumere MTX alla dose di 10 mg/settimana solo in caso di intolleranza a MTX b. Trattamento con idrossiclorochina (200-400 mg/die p.o.) o clorochina (250-500 mg/die p.o.) per almeno 8 settimane prima della visita di screening. |
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E.4 | Principal exclusion criteria |
1. Patients with arthritis due to other autoimmune diseases than RA 2. Any active or ongoing bacterial infections within 4 weeks prior to screening visit, unless treated and resolved with appropriate therapy or any history of recurrent infections or conditions predisposing to chronic infections (e.g., bronchiectasis, chronic osteomyelitis) 3. History of severe, systemic viral or fungal infections within the past 6 months prior to screening visit, unless treated and/or resolved with appropriate therapy 4. Patients with active malignancy within the previous 5 years with the exception of adequately treated and cured basal or squamous cell carcinoma of the skin or cervical carcinoma in situ occurring more than 12 months prior to screening visit 5. Females of childbearing potential who are pregnant or breast feeding or intend to become pregnant 6. Any other disease or clinically significant abnormality in laboratory parameters which, according to the Investigator, might compromise the safety of the patient, interfere with participation in the trial or compromise the trial objective |
1. I pazienti con artrite dovuta a malattie autoimmuni diverse dall’AR 2. Una qualsiasi infezione batterica attiva o in corso nelle 4 settimane che precedono la visita di screening, tranne che se trattate e risolte con adeguata terapia oppure una qualsiasi anamnesi di infezioni ricorrenti o condizioni che predispongano a infezioni croniche (ad es., bronchiectasia, osteomielite cronica) 3. Anamnesi di gravi infezioni micotiche o virali sistemiche, nei 6 mesi precedenti la visita di screening, tranne se trattate e/o risolte con adeguata terapia 4. Pazienti con neoplasia attiva negli ultimi 5 anni, ad eccezione del carcinoma cutaneo basocellulare o squamocellulare adeguatamente trattato e curato o del carcinoma cervicale in situ presente più di 12 mesi prima della visita di screening 5. Donne in età fertile, in stato di gravidanza o allattamento o che desiderano avviare una gravidanza 6. Una qualsiasi altra malattia o anomalia clinicamente significativa risultante dai parametri di laboratorio che, a giudizio dello Sperimentatore, possa compromettere la sicurezza del paziente, interferire con la partecipazione alla sperimentazione o comprometterne l’obiettivo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
ACR20 (defined as 20% improvement in American College of Rheumatology criteria measures) (i.e., responder or non-responder) |
• ACR20 (definito come un miglioramento del 20% nei risultati definiti dai criteri dell’American College of Rheumatology) (ossia, rispondente o non rispondente) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at week 12 |
alla Settimana 12 |
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E.5.2 | Secondary end point(s) |
- ACR20, ACR50 and ACR70 - Change in DAS28-CRP (defined as Disease Activity Score for 28 joints with C-reactive protein measure) from baseline - Simplified Disease Activity Index (SDAI) remission (SDAI of 3.3 or below) - European League Against Rheumatism (EULAR) criteria response - Change from baseline in the overall scores of the following PRO measures: - Health Assessment Questionnaire – Disability Index (HAQ-DI) - Short Form Health Survey (SF-36v2) - Safety endpoint : - Incidence and type of adverse events (AEs) - Radiographic assessments - Change from baseline in van der Heijde sharp score |
- ACR20, ACR50 e ACR70 - Variazione dal basale nel DAS28-CRP (definito come punteggio di attività della malattia per 28 articolazioni, misurati con la proteina C-reattiva [Disease Activity Score for 28 joints with C-reactive protein measure]) - Remissione in base all’indice semplificato di attività della malattia (Simplified Disease Activity Index, SDAI): SDAI pari a 3,3 o inferiore - Risposta in base ai criteri della Lega Europea contro le Malattie Reumatiche (European League Against Rheumatism, EULAR) - Variazione dal basale nei punteggi complessivi delle seguenti misure PRO: -Questionario di valutazione dello stato di salute – Indice di disabilità (Health Assessment Questionnaire Disability Index, HAQ-DI) -Questionario sullo stato di salute 36v2 abbreviato (Short Form-36 Health Survey, SF-36v2) - Endpoint di sicurezza: -Incidenza e tipo di eventi avversi (EA) - Valutazioni radiografiche -Variazione dal basale del punteggio Sharp/van der Heijde |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All key secondary endpoints will be determined at Weeks 12 and 24. Key secondary endpoints during the open label extension (week 52) will be safety and ACR20/50/70. |
Tutti gli endpoint secondari chiave saranno determinati alla settimana 12 e 24. Gli endpoint secondari chiave durante la fase di estensione in aperto (settimana 52) saranno di safety e l'ACR20/50/70. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, describe the potential immunogenicity |
tollerabilità, descrivere la potenziale immunogenicità |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
seguito da un periodo di estensione in aperto |
Followed by an open label extension period |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 52 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
European Union |
Argentina |
Brazil |
Canada |
Mexico |
Russian Federation |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 29 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 29 |
E.8.9.2 | In all countries concerned by the trial days | 0 |