E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Myositis (dermatomyositis [DM] or polymyositis [PM]) |
Miositi: Dermatomiosite (DM) e Polimiosite (PM) |
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E.1.1.1 | Medical condition in easily understood language |
Chronic inflammatory disorders of striated muscle with variable involvement of internal organs |
Patologie infiammatorie croniche del muscolo striato con variabile interessamento degli organi interni |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012503 |
E.1.2 | Term | Dermatomyositis |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028653 |
E.1.2 | Term | Myositis |
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036102 |
E.1.2 | Term | Polymyositis |
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 |
Evaluate the efficacy of TCZ in patients with refractory myositis |
Lo studio si propone di valutare l’efficacia del Tocilizumab nei pazienti con miosite. |
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E.2.2 | Secondary objectives of the trial |
Safety assessment |
Valutazione della sicurezza |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. age 18 years or older 2. capacity to provide a written informed consent 3. fulfil the Bohan and Peter criteria and 1) have the typical rash of DM (heliotrope rash and/or Gottron sign and/or Gottron papules) or 2) have a myositis-specific autoantibody (MSA) or else 3) have the diagnosis confirmed by muscle biopsy 4. have significant muscle weakness (grade 4 or less of the Medical Research Council scale in at least 2 proximal muscle groups) plus have either an elevated muscle enzyme (CK or aldolase) at least 1.3 the upper limit of normal and/or an MRI of the thigh muscles showing edema in fat-suppressed sequences 5. physician’s global assessment of at least 2 (0-10 cm VAS) 6. a patient’s global assessment of at least 2 (0-10 cm VAS) 7. Health assessment questionnaire (HAQ) disability index of at least 0.25 8. signed informed consent form |
1. età di almeno 18 anni 2. capacità di fornire un consenso informato scritto 3. soddisfare i criteri Bohan e Peter per la classificazione delle miositi e 1) avere la tipica eruzione cutanea della DM (eruzione cutanea eliotropa e / o segno di Gottron e / o papule di Gottron) oppure 2) avere un autoanticorpo specifico per miosite (MSA) oppure 3) avere la diagnosi confermata da biopsia muscolare 4. ipostenia muscolare significativa (grado 4 o meno della scala del Medical Research Council in almeno 2 gruppi muscolari prossimali) e almeno un enzima muscolare elevato (CPK o aldolasi) almeno 1,3 al di sopra del limite superiore della normale e / o RMN dei muscoli della coscia mostrante edema muscolare in sequenze a soppressione del grasso 5. valutazione globale del medico di almeno 2 (VAS da 0-10 cm) 6. valutazione globale del paziente di almeno 2 7. Indice di disabilità (HAQ) di almeno 0.25 8. adesione allo studio mediante firma del consenso informato
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E.4 | Principal exclusion criteria |
1. subjects younger than 18 years 2. inability to provide informed consent 3. history of alcohol or recreational drug use within 1 year prior to screening 4. infections, including serious infections requiring hospitalization or treatment with intravenous antibiotics within 4 weeks of screening; 5. positive HbsAg status or positive anti-HCV antibodies; 6. latent untreated TB 7. current malignancies or malignancies diagnosed within the previous 5 years (except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been removed) 8. severe co-morbidities, including immunodeficiency; any comorbidity that in the opinion of the PI may not allow the patients to safely complete the trial 9. initiation of an exercise program for muscle strengthening within 4 weeks of the screening visit and for the whole duration of the trial 10. major surgery 4 weeks prior to study entry or planned major surgery during the study period 11. immunization with a live vaccines within a month before study entry 12. pregnancy and lactation, patients with reproductive potential not willing to use an effective method of contraception 13. previous treatment with TCZ 14. history of severe hypersensitivity reactions to monoclonal antibodies 15. contraindications to having an MRI of the thigh muscles done 16. abnormal laboratory values, including creatinine above the upper limit of normal unless creatinine clearance is above 30 ml/min; white cell count <3,000 mm3, absolute neutrophil count less than 2,000 mm3, absolute lymphocyte count less than 500/mm3, platelet count less than 100,000 and hemoglobin less than 8.5 g/dl. |
1. soggetti di età inferiore ai 18 anni 2. incapacità di fornire un consenso informato, 3. anamnesi positiva per alcolismo o uso di droghe entro un anno prima dello screening, 4. infezioni, incluse infezioni gravi che richiedono ospedalizzazione o trattamento con antibiotici endovenosi entro 4 settimane dalla screening, 5. HbsAg positivo o anticorpi anti-HCV positivi, 6. TBC latente non trattata, 7. tumori maligni diagnosticati nei 5 anni precedenti (ad eccezione del basalioma, carcinoma squamoso della cute o del carcinoma in situ della cervice uterina operato), 8. comorbidità di rilievo, tra cui l'immunodeficienza; qualsiasi comorbidità che a giudizio del PI non possa permettere ai pazienti di completare il trial senza rischi, 9. l'inizio di un programma di esercizi per il rafforzamento muscolare entro 4 settimane dalla visita di screening e per tutta la durata dello studio, 10. intervento chirurgico maggiore 4 settimane prima dell'arruolamento nello studio o intervento maggiore pianificato durante il periodo dello studio, 11. immunizzazione con vaccini vivi entro un mese dall’arruolamento nello studio, 12. gravidanza e allattamento, pazienti con potenzialità riproduttiva che non sono disposti ad utilizzare un metodo efficace di contraccezione, 13. trattamento precedente con TCZ, 14. pregresse reazioni di ipersensibilità grave agli anticorpi monoclonali, 15. controindicazioni all'esecuzione di una risonanza magnetica nucleare dei muscoli della coscia, 16. valori di laboratorio anormali, compresa la creatinina al di sopra del limite superiore del normale, a meno che la clearance della creatinina sia superiore a 30 ml / minuto; conta leucocitaria <3.000 mm3, conta neutrofilica assoluta inferiore a 2.000 mm3, conta linfocitaria assoluta inferiore a 500 / mm3, conta piastrinica inferiore a 100.000 ed emoglobina inferiore a 8.5 g / dl.
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of patients achieving an improvement according to IMACS (International Myositis Assessment and Clinical Studies Group) |
percentuale di pazienti che raggiunge un miglioramento secondo l'IMACS (International Myositis Assessment and Clinical Studies Group) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Weeks 0, 4, 8, 12, 16, 24, 38 and 52 |
settimane 0, 4, 8, 12, 16, 24, 38 e 52 |
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E.5.2 | Secondary end point(s) |
1. time from first treatment to improvement based on IMACS criteria, percentage of patients achieving remission (defined as normal or stable muscle strength with normal levels of muscle enzymes, absence of muscular edema at MRI and absence of active extramuscular manifestations), reduction glucocorticoid dose, significant minimal improvement in cutaneous dermatomyositis, changes in edema at MRI, changes in fatty atrophy at MRI 2. Frequency and type of adverse events |
1. tempo dal primo trattamento al miglioramento in base ai criteri IMACS, percentuale di pazienti che raggiungono la remissione (definita come forza muscolare normale o stabile con i normali livelli degli enzimi muscolari, assenza di edema muscolare alla RMN e assenza di manifestazioni extramuscolari attive), riduzione della dose di glucocorticoidi, miglioramento minimo significativo della dermatomiosite cutanea, cambiamenti nell'edema di MRI, variazioni di atrofia grassosa alla RMN; 2. frequenza e il tipo di eventi avversi |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Weeks 0, 4, 8, 12, 16, 24, 38 and 52 2. Week 0, 4, 8, 12, 16, 24, 38 and 52; any adverse event occurring at any time during the whole study |
1. settimane 0, 4, 8, 12, 16, 24, 38 e 52 2. settimane 0, 4, 8, 12, 16, 24, 38 e 52; ogni evento avverso verificatosi a qualunque tempo durante l’intero studio |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |