E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sjögren’s Syndrome. |
Sindrome di Sjögren. |
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E.1.1.1 | Medical condition in easily understood language |
Autoimmune condition of unknown cause where the body's own self-defenses attack glands that secrete fluids resulting in inflammation of the glands. The inflammatory process can involve other organs. |
Condizione autoimmune di causa sconosciuta in cui le autodifese del corpo attaccano le ghiandole, che secernono fluidi, con conseguente infiammazione delle stesse e di eventuali altri organi. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10040767 |
E.1.2 | Term | Sjogren's syndrome |
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 evaluate the safety and tolerability of iscalimab at two dose levels (600 mg and 300 mg) in patients with Sjögren’s Syndrome, who participated in the TWINSS core study, CCFZ533B2201. |
Valutare la sicurezza e la tollerabilità di iscalimab a 2 diversi dosaggi (600mg e 300mg) in pazienti con Sindrome di Sjögren che hanno partecipato allo studio core TWINSS, CCFZ533B2201. |
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E.2.2 | Secondary objectives of the trial |
1. To assess the pharmacokinetics (PK trough levels) and dose-exposure relationship of iscalimab; 2. To assess immunogenicity of iscalimab. |
1. Valutare la farmacocinetica (livelli pre-somministrazione) e la relazione dose-esposizione di iscalimab; 2. Valutare l’immunogenicità di iscalimab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participants eligible for inclusion in this study must meet all of the following criteria: 1. Participants must have participated in the TWINSS core study, CCFZ533B2201, and must have completed the entire treatment period up to Week 48 and the follow-up period up to Week 60 2. Signed informed consent must be obtained prior to participation in the extension study (i.e. before commencement of the Week 60 assessments of the core study) 3. In the judgement of the Investigator, participants must be expected to clinically benefit from continued iscalimab therapy. |
I partecipanti eleggibili per l’inclusione in questo studio devono rispettare tutti i seguenti criteri: 1. Devono aver partecipato allo studio core TWINSS, CCFZ533B2201, e devono aver completato tutto il periodo di trattamento fino alla settimana 48 e il periodo di follow-up fino alla settimana 60; 2. Il consenso informato deve essere firmato prima della partecipazione allo studio di estensione (prima dell’inizio delle valutazioni dello studio core alla settimana 60); 3. A giudizio dell’investigatore, è atteso per i partecipanti un beneficio clinico dalla terapia continuativa con iscalimab. |
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E.4 | Principal exclusion criteria |
Participants meeting any of the following criteria are not eligible for inclusion in this study. 1. Sjögren’s Syndrome overlap syndromes where another autoimmune rheumatic disease constitutes the principle illness, specifically: • Moderate-to-severe active systemic lupus erythematosus (SLE) with anti-dsDNA positivity and renal involvement, or other organ involvement that impedes on ability to score ESSDAI domains • Active rheumatoid arthritis (RA) that impedes on the ability to score the ESSDAI articular domain • Systemic sclerosis • Any other concurrent connective tissue disease (e.g., lupus nephritis (LN), large vessel vasculitis (LVV), Sharp syndrome (mixed connective tissue disease) that is active and requires immunosuppressive treatment outside the scope of this trial and would impede on Sjögren's Syndrome organ domain assessments 2. Use of other investigational drugs other than iscalimab during the core study 3. Active uncontrolled viral, bacterial or other infections requiring systemic treatment at the time of enrollment, or history of recurrent clinically significant infection or of bacterial infections with encapsulated organisms 4. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human Chorionic Gonadotropin (hCG) laboratory test 5. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 14 weeks after stopping of investigational drug. Highly effective contraception methods include: • Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment • Male sterilization (at least 6 months prior to screening and confirmed as successful). For female patients in the study, the vasectomized male partner should be the sole partner for that patient. In case the vasectomized male partner is not the sole partner of the female patient, highly effective method of contraception must be applied (double barrier contraception is not sufficient) • Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking investigational drug. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment she is considered not of childbearing potential. In case local regulations deviate from the contraception methods listed above, local regulations apply and will be described in the Informed Consent Form (ICF). |
I partecipanti che presentino uno di questi criteri non sono eleggibili per l’inclusione in questo studio: 1. Sindromi da overlap con la Sindrome di Sjögren, nella quale un’altra malattia autoimmune costituisce la malattia principale, ed in particolare: • Lupus Eritematoso Sistemico attivo di entità moderata-severa, con positività per anticorpi anti-dsDNA e coinvolgimento renale, o altro coinvolgimento d’organo che limiti la capacità di valutare lo score ESSDAI; • Artrite Reumatoide attiva, che limiti la capacità di valutare il dominio articolare dello score ESSDAI; • Sclerosi sistemica; • Qualunque altra connettivopatia (esempio: nefrite lupica, vasculite dei grossi vasi, Sindrome di Sharp – malattia mista del tessuto connettivo) che sia attiva e richieda terapia immunosoppressiva al di fuori degli scopi di questo studio, e che possa limitare la valutazione dei domini d’organo della Sindrome di Sjögren. 2. Uso di altri farmaci sperimentali oltre ad iscalimab durante lo studio core. 3. Infezioni virali o batteriche attive e non controllate, o altre infezioni che richiedano terapia sistemica al momento dell’arruolamento, o anamnesi positiva per infezioni ricorrenti clinicamente significative o di infezioni batteriche da organismi capsulati. 4. Donne in gravidanza o allattamento, dove la gravidanza è definita come lo stato di una donna dopo il concepimento e fino al termine della gestazione, confermato dalla positività di un test di laboratorio per la gonadotropina corionica umana (hCG); 5. Donne in età fertile, definite come donne che possono fisiologicamente iniziare una gravidanza, a meno che non stiano utilizzando metodi contraccettivi altamente efficaci durante il trattamento e nelle 14 settimane dopo il termine del trattamento sperimentale. Metodi contraccettivi ad alta efficacia includono: • Astinenza completa dai rapporti sessuali (se in coerenza con lo stile di vita abituale e preferito). L’astinenza periodica (ad esempio, da calendario, ovulatoria, sintotermico, metodi post-ovulatori) e il coito interrotto non sono considerati metodi contraccettivi accettabili; • Sterilizzazione femminile (precedente ooforectomia bilaterale chirurgica con o senza isterectomia), isterectomia totale o legatura delle tube almeno nelle sei settimane precedenti l’inizio della somministrazione del trattamento in studio. Nel caso di sola ooforectomia, lo stato riproduttivo deve essere confermato da una valutazione di follow-up del livello ormonale. • Sterilizzazione maschile (almeno 6 mesi prima dello screening e di successo confermato). Per le partecipanti donne dello studio, il partner maschile vasectomizzato deve essere l’unico partner. Se il partner vasectomizzato non fosse l’unico partner, deve essere utilizzato un metodo anticoncezionale ad alta efficacia. • Impiego di contraccezione ormonale per via orale (estrogeni e progesterone), o utilizzo di un dispositivo intrauterino (IUD) o di un sistema intrauterino (IUS) o di altre forme di contraccezione ormonale di efficacia comparabile (frequenza d’insuccesso < 1%), come ad esempio, anello ormonale vaginale o contraccezione ormonale transdermica. In caso di utilizzo della contraccezione ormonale orale questa deve mantenersi stabile per un minimo di 3 mesi prima dell’assunzione del trattamento in studio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Incidence of Treatment-emergent adverse events (TEAEs)/ serious adverse events (SAEs); - Routine hematology and clinical chemistry laboratory test results at analysis visits up to end of study; - Vital signs at analysis visits up to end of study. |
- Incidenza di eventi avversi rilevanti ai fini del trattamento (TEAE)/ eventi avversi gravi (SAE); - Risultati dei test di laboratorio di ematologia e chimica clinica di routine durante le visite di analisi fino alla fine dello studio; - Segni vitali alle visite di analisi fino alla fine dello studio. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Repeatedly until study completion (60 weeks). |
Ripetutamente fino al completamento dello studio (60 settimane). |
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E.5.2 | Secondary end point(s) |
1. Free iscalimab concentration in plasma during the treatment (Ctrough) and follow-up (up to end of study) periods; 2. Incidence of anti-iscalimab antibodies in plasma at analysis visits up to end of study. |
1. Concentrazione libera di iscalimab nel plasma durante il trattamento (Ctrough) e il follow-up (fino alla fine dello studio); 2. Incidenza di anticorpi anti-iscalimab nel plasma durante le visite di analisi fino alla fine dello studio. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Repeatedly until study completion (60 weeks). |
Ripetutamente fino al completamento dello studio (60 settimane). |
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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 | No |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability and Immunogenicity. |
Tollerabilità e 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Doppio cieco fino al Database Lock finale (DBL) dello studio Core (CFZ533B2201), aperto dopo DBL. |
Double-blind until final database lock (DBL) of Core study (CFZ533B2201), open after DBL. |
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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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 | Information not present in EudraCT |
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 |
Australia |
Brazil |
Canada |
Chile |
Colombia |
Israel |
Japan |
Korea, Republic of |
Russian Federation |
Turkey |
United States |
Austria |
France |
Germany |
Greece |
Hungary |
Italy |
Netherlands |
Portugal |
Romania |
Slovenia |
Sweden |
United Kingdom |
Argentina |
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E.8.7 | Trial 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
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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 | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |