E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Generalized Myasthenia Gravis |
Miastenia Gravis generalizzata |
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E.1.1.1 | Medical condition in easily understood language |
Myasthenia Gravis in patients who have generalized Muscle Weakness |
Miastenia Gravis in pazienti che hanno debolezza muscolare generalizzata |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028417 |
E.1.2 | Term | Myasthenia gravis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the long-term safety and tolerability of efgartigimod PH20 SC in participants with Generalized Myasthenia Gravis (gMG) |
Valutare la sicurezza e la tollerabilità a lungo termine di efgartigimod PH20 SC in partecipanti affetti da Miastenia Gravis generalizzata (generalized Myasthenia Gravis, [gMG]) |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the impact of efgartigimod PH20 SC on disease severity - To evaluate the effect of efgartigimod PH20 SC on Pharmacodynamic (PD) - To evaluate the immunogenicity of efgartigimod PH20 SC |
- Valutare l’impatto di efgartigimod PH20 SC sulla gravità della malattia - Valutare l’effetto di efgartigimod PH20 SC sulla farmacodinamica (Pharmacodynamics, [PD]) - Valutare l’immunogenicità di efgartigimod PH20 SC |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participants are eligible to be included in the study only if all of the following criteria apply: 1. Must be capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol 2. Previously participated in antecedent studies ARGX-113-2001 or ARGX-113-1705 and are eligible for roll over 3. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies and: a. Male participants: - Male participants are not allowed to donate sperm from signing the ICF through 90 days after the last dose of IMP. b. Female participants: - Women of Child bearing potential (WOCBP) must have a negative urine pregnancy test at baseline before IMP can be administered. |
I partecipanti sono idonei all’inclusione nello studio solo se soddisfano tutti i seguenti criteri: 1. Devono essere in grado di fornire un consenso informato firmato, che include la conformità ai requisiti e alle restrizioni elencati nel modulo di consenso informato (Informed Consent Form, [ICF]) e in questo protocollo 2. Devono aver partecipato in precedenza agli studi antecedenti ARGX-113-2001 o ARGX-113-1705 ed essere idonei al roll over 3. L’uso di contraccettivi da parte di uomini e donne deve essere coerente con le normative locali riguardanti i metodi contraccettivi per coloro che partecipano a studi clinici e: a. Partecipanti di sesso maschile: - Ai partecipanti di sesso maschile non è consentita la donazione di sperma a partire dalla firma dell’ICF fino a 90 giorni dopo l’ultima dose di prodotto medicinale sperimentale (Investigational Medicinal Product, [IMP]). b. Partecipanti di sesso femminile: - Le donne in età fertile (Women of Child bearing potential, [WOCBP]) devono presentare un test di gravidanza sulle urine negativo al basale prima della somministrazione di IMP. |
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E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply: 1. The participant was discontinued early from studies ARGX-113-2001 or ARGX-113-1705, unless the reason for discontinuation from study ARGX-113-1705 was to roll over into study ARGX-113-2002 a. Participants who, in the investigator's judgment, are not benefiting from efgartigimod IV in study ARGX-113-1705 Part B are not eligible for roll over into ARGX-113-2002. 2. Are pregnant or lactating, or intend to become pregnant during the study or within 90 days after the last dose of IMP 3. Has any of the following medical conditions: a. Clinically significant uncontrolled chronic bacterial, viral, or fungal infection at screening b. Any other known autoimmune disease that, in the opinion of the investigator, would interfere with accurate assessment of clinical symptoms of myasthenia gravis or put the participant at undue risk c. History of malignancy unless deemed cured by adequate treatment with no evidence of reoccurrence for =3 years before the first administration of IMP. Participants with the following cancers can be included at any time: - adequately treated basal cell or squamous cell skin cancer - carcinoma in situ of the cervix - carcinoma in situ of the breast - incidental histological findings of prostate cancer (TNM classification of malignant tumors stage T1a or T1b) d. Clinical evidence of other significant serious diseases, or the participant has had a recent major surgery, or who have any other condition that, in the opinion of the investigator, could confound the results of the study or put the participant at undue risk. |
I partecipanti saranno esclusi dallo studio se rientreranno in uno qualsiasi dei seguenti criteri: 1. Il partecipante è stato ritirato anticipatamente dagli studi ARGX-113-2001 o ARGX-113-1705, eccetto nel caso in cui la motivazione dell’interruzione dello studio ARGX-113-1705 fosse il roll over nello studio ARGX-113-2002 a. I partecipanti che, a giudizio dello sperimentatore, non stanno traendo beneficio da efgartigimod EV nello studio ARGX-113-1705 Parte B non sono idonei al roll over in ARGX-113-2002. 2. Sono in gravidanza o in allattamento o hanno intenzione di iniziare una gravidanza durante lo studio o entro 90 giorni dall’ultima dose di IMP 3. Presentano una delle seguenti condizioni mediche: a. Infezione batterica, virale o fungina non controllata, cronica, clinicamente significativa al momento dello screening b. Qualsiasi altra malattia autoimmune nota che, secondo l’opinione dello sperimentatore, interferirebbe con una valutazione accurata dei sintomi clinici della Miastenia Gravis o esporrebbe il partecipante a rischio inopportuno c. Anamnesi di neoplasia, a meno che non si ritenga che sia stata curata con un trattamento adeguato e che non vi siano prove di recidiva per =3 anni prima della prima somministrazione dell’IMP. I partecipanti con i seguenti tumori possono essere inclusi in qualsiasi momento: - tumore della pelle basocellulare o squamocellulare adeguatamente trattato - carcinoma della cervice uterina in situ - carcinoma mammario in situ - risultati istologici accidentali di cancro alla prostata (classificazione TNM dei tumori maligni in stadio T1a o T1b) d. Evidenze cliniche di altre malattie gravi e significative o il partecipante ha subito di recente un intervento di chirurgia maggiore o presenta qualsiasi altra condizione che, a parere dello sperimentatore, potrebbe confondere i risultati dello studio o esporre il partecipante a un rischio inopportuno |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Incidence of Serious Adverse Events (SAEs) |
Incidenza di eventi avversi gravi (Serious Adverse Event, [SAE]) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary end point is timeframe 'up to 2 years'. |
L’endpoint primario è l’intervallo di tempo “fino a 2 anni”. |
|
E.5.2 | Secondary end point(s) |
- Percentage reduction in levels of total immunoglobulin G (IgG) from baseline and cycle baseline over time by cycle - Percentage reduction of acetylcholine receptor binding autoantibodies (AChR-Ab) from baseline and cycle baseline over time by cycle in AChRAb seropositive participants - Incidence and prevalence of anti-drug antibodies (ADAs) to efgartigimod over time |
- Riduzione percentuale dei livelli di immunoglobulina G (IgG) totale rispetto al basale e al basale del ciclo nel tempo per ciclo - Riduzione percentuale degli autoanticorpi leganti il recettore dell’acetilcolina (Acetylcholine Receptor Binding Autoantibody, [AChR-Ab]) rispetto al basale e al basale del ciclo nel tempo per ciclo nei partecipanti sieropositivi ad AChRAb - Incidenza e prevalenza di anticorpi anti-farmaco (Anti-Drug Antibody, [ADA]) mirati a efgartigimod nel tempo |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary end points are timeframe 'up to 2 years'. |
Tutti gli endpoint secondari sono periodi di tempo “fino a 2 anni”. |
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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 and Immunogenicity |
Tollerabilità e Immunogenicità |
|
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 |
|
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 | 1 |
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 | 38 |
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 |
Bosnia and Herzegovina |
Canada |
Georgia |
Japan |
Russian Federation |
Serbia |
United States |
Belgium |
Germany |
Hungary |
Italy |
Netherlands |
Poland |
Spain |
United Kingdom |
Czechia |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |