An Open-label Study to Investigate the Clinical Efficacy of Different Dosing Regimens of Efgartigimod IV in Patients With Generalized Myasthenia Gravis (ADAPT NXT)

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

21 Dec 2021 → 7 Oct 2025

Decision date (initial)

2024-09-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

argenx BV

External identifiers

EU CT number

2024-510932-36-00

EudraCT number

2021-002504-12

ClinicalTrials.gov

NCT04980495

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacodynamic, Others, Pharmacokinetic

To assess the clinical efficacy of efgartigimod IV 10 mg/kg administered in a q2w continuous regimen compared to that administered in a cyclic regimen

Secondary objectives 3

1. To evaluate the safety and tolerability of both treatment regimens used throughout the study
2. To assess the clinical efficacy of efgartigimod IV in both treatment regimens over time
3. To compare the number of participants who achieve maximal clinical effect during different treatment regimens

Conditions and MedDRA coding

Generalized Myasthenia Gravis (gMG)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Capable of providing signed informed consent and following with protocol requirements
2. At least 18 years of age, at the time of signing the informed consent.
3. Diagnosed with Generalized Myasthenia Gravis (gMG) with confirmed documentation and supported by a physical exam and confirmed seropositivity for anti-acetylcholine receptor antibodies (AChR-Abs).
4. Meets the clinical criteria as defined by the Myasthenia Gravis Foundation of America (MGFA) class II, III, or IV
5. Has a Myasthenia Gravis – Activities of Daily Living (MG-ADL) total score ≥5 at the time of the study with more than 50% of the score due to nonocular symptoms
6. Concomitant gMG treatment is permitted. Permitted concomitant gMG treatment includes nonsteroidal immunosuppressive drugs (NSIDs), steroids, and/or acetylcholinesterase (AChE) inhibitors. If receiving corticosteroids and/or NSIDs, must be on a stable dose for at least 1 month before the study.
7. Agrees to use contraceptive measures consistent with local regulations and: o Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test before receiving the study drug.

Exclusion criteria 10

1. Any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of the clinical symptoms of gMG and/or put the participant at undue risk
2. The participant has been institutionalized due to an official or judicial order.
3. History of malignancy unless deemed cured by adequate treatment with no evidence of reoccurrence for ≥3 years before the first administration of the study drug. 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 finding of prostate cancer (TNM stage T1a or T1b)
4. Clinical evidence of other significant serious diseases, a recent (<3 months) major surgery, or any other condition that, in the opinion of the investigator, could confound the results of the study or put the participant at undue risk
5. A thymectomy within 3 months of screening
6. Pregnant or lactating state or intention to become pregnant during the study or within 90 days of the last dose of the study drug
7. Use of the following prior or concomitant therapies: a. intravenous immunoglobulin (IVIg) or subcutaneous immunoglobulin (SCIg) within 14 days of day 1; b. Rituximab within 6 months of day 1; c. Eculizumab within 1 month of day 1; d. Other monoclonal antibodies (eg, adalimumab, tocilizumab, ixekizumab) within 5 half-lives of the monoclonal antibodies before day 1; e. Use of any other investigational product within 3 months or 5 half-lives, whichever is longer, before day 1; f. Receipt of a live or live-attenuated vaccines received within 4 weeks of screening. Previous participation in a clinical study or patient access program during which they were treated with efgartigimod.
8. Known hypersensitivity reaction to efgartigimod or any of its excipients
9. The participant stands in any relationship of dependency with the sponsor.
10. Clinically significant active infection that is not sufficiently resolved in the investigator’s opinion or positive serum test at time of the study for active infection with any of the following:  Hepatitis B virus (HBV), Hepatitis C virus (HCV), HIV

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean of the average MG-ADL total score change from baseline during the visit of week (W)1 through W21 by regimen arm

Secondary endpoints 7

1. Incidence and severity of AEs, incidence of serious adverse events (SAEs), incidence of AESIs, and changes in laboratory test results, vital sign measurements, and electrocardiogram results
2. Change from baseline in the MG-ADL total score over time
3. Normalized area under the effect curve (AUEC) of MG-ADL total score improvement from baseline during the following intervals: day 1 through W7; W7 through W14; W14 through W21; W7 through W21
4. Characterization of MG-ADL total score change from baseline during the following 5 intervals using mean and standard deviation: W1 through W7; W8 through W14; W15 through W21; W8 through W21; W1 through W21
5. Number and percentage of participants who have a ≥ 2, 3, 4, or 5 points improvement in MG-ADL total score from baseline during the following 5 intervals: W1 through W7; W8 through W14; W15 through W21; W8 through W21; W1 through W21
6. Percentage of time participants have a reduction in MG-ADL total score of at least 2 points from baseline during W4 through W21
7. Number and percentage of participants who achieve minimal symptom expression (MSE), defined as a MG-ADL total score of 0 or 1, in the following 5 intervals: W1 through W7; W8 through W14; W15 through W21; W8 through W21; W1 through W21

Investigational products

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

Test 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 11

Locations

7 EU/EEA countries · 17 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 36 files

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

Application history

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