A Phase 3 study to evaluate the Efficacy and Safety of Efgartigimod IV in Patients with Acetylcholine Receptor Binding Antibody Seronegative Generalized Myasthenia Gravis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Argenx

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

16 Oct 2024 → ongoing

Decision date (initial)

2024-10-02

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

argenx BV

External identifiers

EU CT number

2024-511796-15-00

ClinicalTrials.gov

NCT06298552

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Pharmacodynamic

To determine the efficacy of efgartigimod IV compared to placebo in participants with AChR-Ab seronegative gMG in part A

Secondary objectives 3

1. 1.To determine the efficacy of efgartigimod IV compared to placebo, and the long-term efficacy of efgartigimod IV in participants with AChR-Ab seronegative gMG.
2. 2.To assess the safety and tolerability of efgartigimod IV compared to placebo and the long-term safety and tolerability of efgartigimod IV in participants with AChR-Ab seronegative gMG.
3. 3.To assess the PD effect of efgartigimod IV in participants with AChR-Ab seronegative gMG.

Conditions and MedDRA coding

Acetylcholine Receptor Binding Antibody Seronegative Generalized Myasthenia Gravis

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1.Is at least 18 years of age and the local legal age of consent for clinical studies when signing the ICF.
2. 2.The participant is capable of providing signed informed and complying with protocol requirements
3. 3.The participant agrees to use contraceptive measures consistent with local regulations and the women of child-bearing potential (WOCBP) must have a negative serum pregnancy test result at screening and a negative urine pregnancy test result at baseline before receiving the investigational medicinal product (IMP).
4. 4.The participant has no known weakness in infancy and later develop fatigable weakness after aged 16 years and diagnosed with acquired gMG of both of the following: a) History of abnormal neuromuscular transmission demonstrated by single fiber electromyography or repetitive nerve stimulation (RNS) or is anti-muscle-specific kinase antibodies (MuSK-Ab) seropositive b) Either a history of positive edrophonium chloride test OR a demonstrated improvement in MG signs with treatments such as oral acetylcholinesterase (AChE) inhibitors, plasma exchange (PLEX), immunoabsorption, or intravenous immunoglobulin (IVIg)/ subcutaneous immunoglobulin (SCIg) treatment.
5. 5.The participant is receiving a stable dose of MG therapy before screening that includes acetylcholinesterase (AChE) inhibitors, steroids, or nonsteroidal immunosuppressive therapies (NSISTs) in combination or alone.

Exclusion criteria 11

1. 1.Known autoimmune disease or any medical condition that would interfere with an accurate assessment of clinical symptoms of gMG or puts the participant at undue risk
2. 2.History of malignancy unless considered cured by adequate treatment with no evidence of recurrence for ≥ 3 years before first investigational medicinal product (IMP) administration. Adequately treated participants with the following cancers can be included at any time: 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.
3. 3.Clinically significant active infection that is not sufficiently resolved before baseline in the investigator's opinion or positive serum test at screening for active infection with any of the following: Hepatitis B virus (HBV), Hepatitis C virus (HCV), HIV.
4. 4.Current participation in another interventional clinical study or previous participation in an efgartigimod clinical study and received at least 1 dose of investigational medicinal product (IMP)
5. 5.Known hypersensitivity to investigational medicinal product (IMP) or any of its excipients
6. 6.History of or current alcohol, drug, or medication abuse as assessed by the investigator
7. 7.Pregnant or lactating state or intention to become pregnant during the study
8. 8. Live or live-attenuated vaccine received less than 4 weeks before screening
9. 9.Worsening muscle weakness secondary to concurrent infections or medications
10. 10. Received a thymectomy less than 3 months before screening or thymectomy is planned during the study
11. 11.Use of some medications before screening (more information is captured in the protocol)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. MG-ADL total score change from baseline to day 29 in part A

Secondary endpoints 2

1. • QMG total score change from baseline to day 29 in part A
2. • Proportion of participants who are both MG-ADL and QMG responders in part A

Investigational products

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

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Argenx

Sponsor organisation

Argenx

Address

Industriepark-Zwijnaarde 7

City

Gent

Postcode

9052

Country

Belgium

Scientific contact point

Organisation

Argenx

Contact name

Chief Scientific Officer

Public contact point

Organisation

Argenx

Contact name

Vice President Clinical Development

Third parties 14

Locations

15 EU/EEA countries · 48 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 87 files

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

Application history

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