E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Generalized Myasthenia Gravis |
Miastenia grave generalizada |
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E.1.1.1 | Medical condition in easily understood language |
Myasthenia Gravis in patients who have generalized Muscle Weakness |
Miastenia grave en pacientes que tienen debilidad muscular generalizada |
|
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) |
Evaluar la seguridad y la tolerabilidad a largo plazo de efgartigimod PH20 SC en participantes con miastenia grave generalizada (MGg) |
|
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 |
• Evaluar el efecto de efgartigimod PH20 SC sobre la gravedad de la enfermedad • Evaluar el efecto de efgartigimod PH20 SC sobre la farmacodinamia (FD) • Evaluar la inmunogenicidad de 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. |
Únicamente podrán ser incluidos en el estudio los participantes que cumplan todos los criterios siguientes: 1. Capacidad para otorgar el consentimiento informado firmado, lo que incluye el cumplimiento de los requisitos y restricciones que se recogen en el documento de consentimiento informado (DCI) y en este protocolo 2. Participación previa en los estudios precedentes ARGX-113-2001 o ARGX-113-1705 y elegibilidad para la continuación 3. El uso de anticonceptivos en varones y mujeres debe cumplir la normativa local sobre métodos anticonceptivos para participantes en estudios clínicos, y: a. Varones participantes: - Los varones no podrán donar semen desde la firma del DCI hasta 90 días después de la última dosis del PEI. b. Mujeres participantes: - Las mujeres con capacidad reproductiva (MCCR) deberán tener un resultado negativo en una prueba de embarazo en orina realizada en el momento basal antes de poder administrar el PEI. |
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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 |
Quedará excluido del estudio todo candidato que cumpla alguno de los criterios siguientes: 1. El participante fue retirado prematuramente de los estudios ARGX-113-2001 o ARGX-113-1705, a menos que el motivo de la retirada del estudio ARGX-113-1705 fuera incorporarse al estudio ARGX-113-2002 a. Los participantes que, en opinión del investigador, no se estén beneficiando de efgartigimod IV en la parte B del estudio ARGX-113-1705 no son elegibles para pasar a ARGX-113-2002. 2. Mujer embarazada o en período de lactancia, o que tiene intención de quedarse embarazada durante el estudio o en los 90 días siguientes a la última dosis del PEI. 3. Presencia de alguna de las condiciones médicas siguientes: a. Infección bacteriana, viral o micótica o crónica, no controlada y clínicamente significativa en el período de selección. b. Cualquier otra enfermedad autoinmunitaria conocida que, en opinión del investigador, podría interferir en una evaluación exacta de los síntomas clínicos de la miastenia grave o suponer un riesgo excesivo para el participante. c. Antecedentes de neoplasia maligna, a menos que se considere curada con un tratamiento adecuado sin signos de reaparición durante ≥ 3 años antes de la primera administración del PEI. Se podrá incluir a participantes a que hayan tenido los cánceres siguientes en cualquier momento: - Carcinoma basocelular o espinocelular de piel tratado adecuadamente. - Carcinoma in situ de cuello uterino. - Carcinoma in situ de mama. - Hallazgos histológicos fortuitos de cáncer de próstata (estadio T1a o T1b según la clasificación TNM de tumores malignos). d. Evidencia clínica de otras enfermedades graves significativas o el participante se ha sometido recientemente a una intervención de cirugía mayor, o presencia de cualquier otro proceso que, en opinión del investigador, podría confundir los resultados del estudio o suponer un riesgo excesivo para el participante |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Incidence of Serious Adverse Events (SAEs) |
• Incidencia de acontecimientos adversos graves (AAGs) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary end point is timeframe 'up to 2 years'. |
El criterio de valoración principal es en el marco de tiempo "hasta 2 años". |
|
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 AChR-Ab seropositive participants • Incidence and prevalence of anti-drug antibodies (ADAs) to efgartigimod over time |
• Reducción porcentual de los niveles de inmunoglobulina G (IgG) total a lo largo del tiempo con respecto al momento basal y al momento basal de cada ciclo • Reducción porcentual de autoanticuerpos anti-receptor de acetilcolina (AcRAC) a lo largo del tiempo con respecto al momento basal y al momento basal de cada ciclo en los participantes seropositivos para AcRAC • Incidencia y prevalencia de anticuerpos antifármaco (AAF) contra efgartigimod a lo largo del tiempo |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary end points are timeframe 'up to 2 years'. |
Todos los criterios de valoración secundarios son en el marco de tiempo "hasta 2 años". |
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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 |
Tolerabilidad e inmunogenicidad |
|
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 | 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.8.2.4 | 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 | 4 |
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 | 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 |
Bosnia and Herzegovina |
Canada |
Georgia |
Japan |
Russian Federation |
Serbia |
United States |
Belgium |
Germany |
Hungary |
Italy |
Netherlands |
Poland |
Spain |
United Kingdom |
Czechia |
|
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
|
LVLS |
Última visita del último paciente |
|
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |