Clinical trial • Phase II/III • Immunology|Neurology

EFGARTIGIMOD ALFA for Generalized myasthenia gravis

Phase II/III trial of EFGARTIGIMOD ALFA for Generalized myasthenia gravis. open-label, none/not specified-controlled. 7 participants.

Overview

Trial Therapeutic Area
Immunology|Neurology
Trial Disease
Generalized myasthenia gravis
Trial Stage
Phase II/III
Drug Modality
Peptide/protein/enzyme
Paediatric Trial
Yes
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
05-06-2024
First CTIS Authorization Date
24-06-2024

Trial design

open-label, none/not specified-controlled Phase II/III trial in Spain, Belgium, Poland and others.

Open Label
Yes
Comparator
None/Not specified
Target Sample Size
7

Eligibility

Recruits 7 paediatric patients.

Vulnerable Population
The trial enrols children aged 2 to <18 years (paediatric population). Informed consent must be provided by the participant and/or his/her legally authorized representative; assent is required where applicable. Age-specific parent/guardian consent and pediatric assent forms are provided (multiple age-band assent forms available).

Inclusion criteria

  • {"criterion_text":"- Ability of the participant and/or his/her legally authorized representative to understand the requirements of the trial and provide written informed consent/assent, if applicable, willingness and ability to comply with the trial protocol procedures."}
  • {"criterion_text":"- Male or female participants between 2 to < 18 years of age at the time of providing informed consent/assent."}
  • {"criterion_text":"- Diagnosed with gMG with confirmed documentation"}
  • {"criterion_text":"- Meeting the clinical criteria as defined by the Myasthenia Gravis Foundation of America (MGFA) class II, III, and IVa."}
  • {"criterion_text":"- Eligible participants should have an unsatisfactory response (efficacy and/or safety) to immunosuppressants, steroids or AChE inhibitors and should be on stable concomitant gMG therapy of adequate duration before screening."}
  • {"criterion_text":"- Positive serologic test for anti-AChR antibodies at screening (for younger participants (<15kg) historical values can be used)."}

Exclusion criteria

  • {"criterion_text":"- Participants with MGFA class I, IVb, and V."}
  • {"criterion_text":"- Worsening muscle weakness secondary to concurrent infections or medications (aminoglycosides, fluoro-quinolones, beta-blockers, etc)."}
  • {"criterion_text":"- A documented lack of clinical response to plasma exchange (PLEX)."}
  • {"criterion_text":"- Received a live or live-attenuated vaccine fewer than 28 days before screening. (Receiving an inactivated, subunit, polysaccharide, or conjugate vaccine any time before screening is not exclusionary.)"}
  • {"criterion_text":"- Received a thymectomy <3 months before screening or 1 is planned to be performed during the trial period."}
  • {"criterion_text":"- A known hypersensitivity reaction to efgartigimod or any of its excipients."}
  • {"criterion_text":"- Current participation in another interventional clinical trial."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Efgartigimod concentrations as input for compartmental, model-driven analysis to determine age and size dependency of clearance and volume of distribution","definition_or_measurement_approach":"Measurement of efgartigimod serum concentrations to be used as input for compartmental, model-driven PK analysis to determine age- and size-dependency of clearance (CL) and volume of distribution (Vd)."}
  • {"endpoint_text":"- PD parameters: total IgG levels and anti-acetylcholine receptors antibodies (AChR-Ab) as input for PK/PD modeling analysis","definition_or_measurement_approach":"Measurement of total IgG and anti-AChR antibody levels for PK/PD modelling (used as PD input parameters)."}

Secondary endpoints

  • {"endpoint_text":"- Incidence and severity of AEs, incidence of serious AEs (SAEs), incidence of AEs of special interest (AESIs), and changes in laboratory test results, physical examination results, vital sign measurements, and electrocardiogram (ECG) (part B only for ECGs)","definition_or_measurement_approach":"Safety monitoring via AE/SAE/AESI reporting and serial laboratory tests, physical exams, vital signs and ECGs (ECGs specified for part B)."}
  • {"endpoint_text":"- Efgartigimod serum concentrations","definition_or_measurement_approach":"Measurement of serum efgartigimod concentrations over time (PK sampling)."}
  • {"endpoint_text":"- Levels of total IgG and AChR-Ab: absolute values, change from baseline and percent (%) change from baseline","definition_or_measurement_approach":"Quantification of total IgG and anti-AChR antibody levels with assessment of absolute values and change from baseline (including percent change)."}
  • {"endpoint_text":"- Incidence and prevalence of antidrug antibodies (ADAs) against efgartigimod","definition_or_measurement_approach":"Assessment of ADA occurrence and prevalence via immunogenicity assays."}
  • {"endpoint_text":"- MG-ADL total score: absolute value and change from baseline total MG-ADL score","definition_or_measurement_approach":"Clinical efficacy assessment using MG-ADL total score (absolute and change from baseline)."}
  • {"endpoint_text":"- Total QMG score: absolute value and change from baseline","definition_or_measurement_approach":"Clinical efficacy assessment using quantitative myasthenia gravis (QMG) total score (absolute and change from baseline)."}
  • {"endpoint_text":"- Total score EQ-5D-Y: absolute value and change from baseline","definition_or_measurement_approach":"Health-related quality of life measured by EQ-5D-Y total score (absolute and change from baseline)."}
  • {"endpoint_text":"- Quality of Life in Neurological Disorders (Neuro-QoL) Pediatric Fatigue Score: values and change from baseline","definition_or_measurement_approach":"Assessment of pediatric fatigue using Neuro-QoL Pediatric Fatigue Score (values and change from baseline)."}
  • {"endpoint_text":"- Change in protective antibody titers to vaccines received before or received during the trial","definition_or_measurement_approach":"Measurement of protective antibody titers to vaccines to assess changes pre- and post-treatment."}

Recruitment

Planned Sample Size
7
Recruitment Window Months
65
Consent Approach
Informed consent is required from participants and/or their legally authorized representative (parent/guardian) with written consent; assent is required where applicable. Age-specific assent and parent/guardian consent forms are provided (multiple pediatric assent forms for age bands such as 2–6, 7–9, 10–13, 14–17, and adolescent assent forms). Consent/assent documents are available in multiple languages (examples in the dossier include English, Dutch, French, German, Italian, Polish, Spanish).

Geography

Total Number Of Sites
13
Total Number Of Participants
12

Spain

Earliest CTIS Part Ii Submission Date
23-05-2024
Latest Decision Or Authorization Date
01-08-2025
Processing Time Days
435
Number Of Sites
2
Number Of Participants
1

Sites

Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Servicio de Neurología
Principal Investigator Name
Teresa Sevilla Mantecón
Principal Investigator Email
sevilla_ter@gva.es
Contact Person Name
Teresa Sevilla Mantecón
Contact Person Email
sevilla_ter@gva.es
Site Name
Sant Joan De Deu Barcelona Hospital
Department Name
Unidad de Enfermedades Neuromusculares
Principal Investigator Name
Andrés Nascimento Osorio
Principal Investigator Email
andres.nascimento@sjd.es
Contact Person Name
Andrés Nascimento Osorio
Contact Person Email
andres.nascimento@sjd.es

Belgium

Earliest CTIS Part Ii Submission Date
16-05-2024
Latest Decision Or Authorization Date
01-08-2025
Processing Time Days
442
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Universitair Ziekenhuis Antwerpen
Department Name
Neurology
Principal Investigator Name
Diane Beysen
Principal Investigator Email
diane.beysen@uza.be
Contact Person Name
Diane Beysen
Contact Person Email
diane.beysen@uza.be

Poland

Earliest CTIS Part Ii Submission Date
21-05-2024
Latest Decision Or Authorization Date
05-08-2025
Processing Time Days
441
Number Of Sites
3
Number Of Participants
5

Sites

Site Name
Uniwersyteckie Centrum Kliniczne
Department Name
Klinika Neurolgii Rozwojowej
Principal Investigator Name
Maria Mazurkiewicz-Bełdzińska
Principal Investigator Email
mmazur@gumed.edu.pl
Contact Person Name
Maria Mazurkiewicz-Bełdzińska
Contact Person Email
mmazur@gumed.edu.pl
Site Name
Neurologia Śląska Centrum Medyczne
Principal Investigator Name
Marek Andrzej Śmiłowski
Principal Investigator Email
marek.smilowski@neurologiaslaska.pl
Contact Person Name
Marek Andrzej Śmiłowski
Site Name
Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego
Department Name
Centralny Szpital Kliniczny, Klinika Neurologii
Principal Investigator Name
Anna Kostera-Pruszczyk
Principal Investigator Email
anna.kostera-pruszczyk@wum.edu.pl
Contact Person Name
Anna Kostera-Pruszczyk

Germany

Earliest CTIS Part Ii Submission Date
17-05-2024
Latest Decision Or Authorization Date
17-04-2026
Processing Time Days
700
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Sozialpädiatrisches Zentrum (SPZ) Neuropädiatrie
Principal Investigator Name
Claudia Weiß
Principal Investigator Email
claudia.weiss@charite.de
Contact Person Name
Claudia Weiß
Contact Person Email
claudia.weiss@charite.de

France

Earliest CTIS Part Ii Submission Date
15-05-2024
Latest Decision Or Authorization Date
04-05-2026
Processing Time Days
719
Number Of Sites
2
Number Of Participants
1

Sites

Site Name
Hopital Necker Enfants Malades
Department Name
Service de Neuropédiatrie
Principal Investigator Name
Isabelle Desguerre
Principal Investigator Email
isabelle.desguerre@aphp.fr
Contact Person Name
Isabelle Desguerre
Contact Person Email
isabelle.desguerre@aphp.fr
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Centre Hospitalier Universitaire (CHU) Hôpital de La Timone Service de neuro-métabolisme pédiatrique
Principal Investigator Name
Cécile Halbert
Principal Investigator Email
cecile.halbert@ap-hm.fr
Contact Person Name
Cécile Halbert
Contact Person Email
cecile.halbert@ap-hm.fr

Italy

Earliest CTIS Part Ii Submission Date
23-05-2024
Latest Decision Or Authorization Date
08-05-2026
Processing Time Days
715
Number Of Sites
3
Number Of Participants
1

Sites

Site Name
University Of Bari Aldo Moro
Department Name
Neuropsichiatria Infantile
Principal Investigator Name
Emilia Matera
Principal Investigator Email
emilia.matera@uniba.it
Contact Person Name
Emilia Matera
Contact Person Email
emilia.matera@uniba.it
Site Name
IRCCS Istituto Giannina Gaslini
Department Name
Pediatric Neurology
Principal Investigator Name
Chiara Fiorillo
Principal Investigator Email
chiara.fiorillo@edu.unige.it
Contact Person Name
Chiara Fiorillo
Contact Person Email
chiara.fiorillo@edu.unige.it
Site Name
Azienda Ospedaliera Universitaria Meyer IRCCS
Department Name
Neurologia pediatrica
Principal Investigator Name
Renzo Guerrini
Principal Investigator Email
renzo.guerrini@meyer.it
Contact Person Name
Renzo Guerrini
Contact Person Email
renzo.guerrini@meyer.it

Netherlands

Earliest CTIS Part Ii Submission Date
21-05-2024
Latest Decision Or Authorization Date
15-05-2026
Processing Time Days
724
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Leids Universitair Medisch Centrum (LUMC)
Department Name
Neurology
Principal Investigator Name
Erik H. Niks
Principal Investigator Email
Myasthenie@Lumc.nl
Contact Person Name
Erik H. Niks
Contact Person Email
Myasthenie@Lumc.nl

Sponsor

Primary sponsor

Full Name
Argenx
Organisation Type
Pharmaceutical company
Country Of Registered Address
Belgium

Contract research organisations

Name
PPD Development LP
Responsibilities
Vendor Management; multiple operational vendor roles (codes and values listed in sponsor duties)
Name
IQVIA Limited
Responsibilities
Clinical trial support; contact eu_clinical_trials_information@iqvia.com (code 8)
Name
Endpoint Clinical Inc.
Responsibilities
Electronic data capture / clinical technology (support)
Name
Fisher Clinical Services GmbH
Responsibilities
IMP packaging, labelling, storage and distribution; QP release
Name
SGS Belgium
Responsibilities
DSMB support and multiple laboratory/operational services

Third parties

  • {"country":"Switzerland","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"IMP packaging, labelling, storage and distribution","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"code 3","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Labelling, QP release, storage and distribution","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"IQVIA Laboratories LLC","duties_or_roles":"Vaccine protective antibody titers","organisation_type":"Industry"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ECG analysis/review. This vendor will provide Cardiac Safety Services for PPD","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"code 8","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"SGS Belgium","duties_or_roles":"codes 10,13,15 (DSMB support),5,6,7","organisation_type":"Pharmaceutical company"}
  • {"country":"France","full_name":"SGS France","duties_or_roles":"Analysis of PK, PD and ADA; code 4","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"Long term storage of study samples","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"multiple roles including Vendor Management (codes: 1,11,12,13,15,2,5,8 as listed)","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"The Doctors Laboratory Limited","duties_or_roles":"AChR analysis","organisation_type":"Laboratory/Research/Testing facility"}

Investigational products

Investigational Product Name
Vyvgart 20 mg/mL concentrate for solution for infusion
Active Substance
EFGARTIGIMOD ALFA
Modality
Peptide/protein/enzyme
Routes Of Administration
Intravenous infusion
Route
Intravenous infusion
Authorisation Status
Marketing authorisation EU/1/22/1674/001 (authorised product referenced in dossier)
Orphan Designation
Yes
Maximum Dose
1200 mg (max daily dose amount as listed)

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