Efficacy and tolerability of efgartigimod as early treatment in patients with generalized myasthenia gravis.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bellvitge University Hospital, Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

7 Apr 2025 → ongoing

Decision date (initial)

2024-12-05

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of efgartigimod as early treatment in patients with MGg and anti-AChR antibodies, using the activities of daily living in myasthenia gravis (MG-ADL) scale.

Secondary objectives 15

1. To analyze the efficacy of efgartigimod as early treatment in patients with MGg and anti-AChR antibodies, using the activities of daily living scale in myasthenia gravis (MG-ADL).
2. To analyze the usefulness of efgartigimod as early treatment in patients with MGg and anti-AChR antibodies, using the quantitative myasthenia gravis (QMG) scale.
3. To analyze the usefulness of efgartigimod as early treatment in patients with MGg and anti-AChR antibodies, using the myasthenia gravis composite scale (MGC).
4. To evaluate the time to onset of efgartigimod efficacy, defined as the time at which an improvement of 2 or more points on the MG-ADL scale is achieved.
5. To evaluate the time to onset of efgartigimod efficacy, defined as the time at which an improvement of 3 or more points on the QMG scale is achieved.
6. To evaluate the time to onset of efgartigimod efficacy, defined as the time at which an improvement of 3 or more points on the MGC scale is achieved.
7. To evaluate the proportion of early responders on the MG-ADL scale.
8. To evaluate the quality of life perceived by patients with MGg and anti-AChR antibodies who receive early treatment with efgartigimod, using the 15-item myasthenia gravis quality of life scale (MG-QOL15r) and the quality of life scale related to health EQ-5D-5L from the EuroQoL group (EuroQoL-EQ-5D-5L).
9. To collect data on steroid tapering in patients with MGg and anti-AChR antibodies receiving early treatment with efgartigimod.
10. Analyze changes in global IgG levels and in the different IgG subclasses throughout the study.
11. Analyze the evolution of anti-AChR antibody titers throughout the study.
12. Describe the number and percentage of patients who require more than one cycle of treatment with efgartigimod.
13. Describe the number and percentage of patients who require rescue treatment with IVIG and/or plasmapheresis.
14. Describe the number of patients who require hospital admission (and the reason for this).
15. Describe adverse events during the study (if any), assessing their severity and their potential relationship with efgartigimod.

Conditions and MedDRA coding

Patients affected by generalized myasthenia gravis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Adult patients ≥ 18 years of age, of both sexes.
2. Confirmed diagnosis of myasthenia gravis by a neurologist with experience in the disease [clinical symptoms suggestive of MG and positive anti-AChR antibodies and/or an electrophysiological study suggestive of neuromuscular junction disorder]
3. Myasthenia Gravis Foundation of America (MGFA) Class II, III, or IV at the time of the screening visit.
4. Clinical presentation with 5 or more points (more than 50% of the points for non-ocular symptoms) on the MG-ADL scale.
5. Not having received prior immunosuppressive treatment for MG with the exception of corticosteroids that will be started during the study(naïve patients)
6. Women of childbearing potential must have a negative serum pregnancy test at screening, be required to use contraception during the study and for 90 days after the last dose of drug, and agree not to donate eggs during the same period.
7. Men, agree to use adequate contraception and not donate sperm until the end of the study (and/or until 90 days after the last drug infusion).
8. Signed Informed Consent Form.

Exclusion criteria 15

1. MGFA Class I or V.
2. Presence of symptoms that may endanger the patient's life if immediate rescue treatment is not instituted (intravenous immunoglobulins -I VIG- or plasma exchange/plasmapheresis), according to the treating physician's criteria.
3. Having received any immunosuppressive treatment for MG previously.
4. Treatment with IVIG or plasmapheresis within 4 weeks prior to the screening visit.
5. Treatment with rituximab or eculizumab within 6 months prior to the screening visit.
6. Treatment with any monoclonal antibody at the time of the screening visit.
7. History of thymectomy prior to the screening visit or having a thymectomy scheduled during the planned weeks of the study.
8. Have any surgical intervention scheduled during the planned weeks of the study.
9. Active or chronic uncontrolled and clinically significant bacterial, viral or fungal infection at the time of the screening visit.
10. Active hepatitis B, or positivity for hepatitis C (unless treated and cured) and/or HIV at screening.
11. Known autoimmune or non-autoimmune disease that, in the opinion of the treating physician, would interfere with an accurate evaluation of the clinical symptoms of MG or place the patient at undue risk.
12. History of malignancy, unless considered cured with adequate treatment and no evidence of recurrence for ≥ 3 years. (Patients in whom adequate treatment of basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast, or incidental histological finding of prostate cancer -stage can be included at any time). TNM T1a or T1b-).
13. Have received a live or attenuated vaccine during the month prior to the screening visit.
14. Be pregnant and/or breast-feeding or intend to become pregnant during the study or within 90 days of the final dose of efgartigimod.
15. Inability to understand informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients with MGg and anti-AChR antibody responders in MG-ADL after a full course of efgartigimod in combination with the usual prednisone initiation regimen.

Secondary endpoints 17

1. Total score (per patient) and mean total score on the MG-ADL and mean change in the total score on the MG-ADL at weeks 4, 6, 8, 16 and 28, compared to the baseline score.
2. Total score (per patient) and mean total QMG score and mean change in total QMG at weeks 4, 6, 8, 16 and 28, compared to baseline score.
3. Proportion of responding patients in the QMG.
4. Total score (per patient) and mean total MGC score and mean change in total MGC at weeks 4, 6, 8, 16 and 28, compared to baseline score.
5. Proportion of responding patients in the MGC.
6. Median time to onset of efficacy of efgartigimod, determined by when an improvement of 2 or more points on the MG-ADL scale is achieved.
7. Median time of onset of efficacy of efgartigimod, determined by the time at which an improvement of 3 or more points on the QMG scale is achieved.
8. Median time of onset of efficacy of efgartigimod, determined by the time at which an improvement of 3 or more points on the MGC scale is achieved.
9. Proportion of early responders on the MG-ADL scale.
10. Total score (per patient) and mean total score and mean change in total scores in the MG-QOL15r and in the EQ-5D-5L at weeks 4, 6, 8, 16 and 28, compared to the baseline score.
11. Dose of steroids (prednisone) that patients are taking at 4, 6, 8, 16, and 28 weeks after starting treatment (day of first infusion of efgartigimod cycle/baseline visit).
12. Global levels of IgG, and of the different IgG subclasses, at the screening visit and at weeks 2, 4, 8, 16 and 28 after starting treatment (day of the first infusion of the efgartigimod cycle/baseline visit ).
13. Levels of anti-AChR antibody titers at the screening visit and at weeks 2, 4, 6, 8, 16 and 28 after starting treatment (day of the first infusion of the efgartigimod cycle/baseline visit).
14. Number and percentage of patients receiving more than one cycle of efgartigimod.
15. Number and percentage of patients receiving rescue treatment with IVIG and/or plasmapheresis.
16. Number and percentage of patients requiring hospital admission (with description of the causes with number and percentage of them).
17. Number, percentage, description and severity of adverse events.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bellvitge University Hospital

Sponsor organisation

Bellvitge University Hospital

Address

Carrer De La Feixa Llarga S/N

City

L'Hospitalet De Llobregat

Postcode

08907

Country

Spain

Scientific contact point

Organisation

Bellvitge University Hospital

Contact name

Carlos Casasnovas

Public contact point

Organisation

Bellvitge University Hospital

Contact name

Carlos Casasnovas

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Sponsor organisation

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Address

Avinguda De La Gran Via De L'hospitalet 199

City

L'Hospitalet De Llobregat

Postcode

08908

Country

Spain

Scientific contact point

Organisation

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Contact name

Yaiza Hermoso

Public contact point

Organisation

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Contact name

Yaiza Hermoso

Sponsor responsibilities

Article 77 compliance

Bellvitge University Hospital

Contact point sponsor

Bellvitge University Hospital

Article 77 implementation

Bellvitge University Hospital

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications