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

Generalized Myasthenia Gravis Clinical Trial

— ADAPT NXT  

Official title:

A Phase 3b, Randomized, Open-label, Parallel-Group Study to Evaluate Different Dosing Regimens of Intravenous Efgartigimod to Maximize and Maintain Clinical Benefit in Patients With Generalized Myasthenia Gravis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04980495
• Other study ID #: ARGX-113-2003
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 16, 2021
• Est. completion date: May 2026

Study information

• Verified date: March 2024
• Source: argenx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this open-label study is to investigate the efficacy, safety, and tolerability of a continuous regimen of efgartigimod compared with a cyclic regimen in participants with Generalized Myasthenia Gravis (gMG).

Study details include:

The study duration will be up to 138 weeks (including screening and a safety follow-up of up to 9 weeks)

• Part A (regimen comparison period) - 21 weeks

• Part B (extension period) - up to 105 weeks

The visit frequency, including virtual visits, will be weekly through Week 21 and every 5 weeks for the remainder of the study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 69
• Est. completion date: May 2026
• Est. primary completion date: August 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

• At least 18 years of age, at the time of signing the informed consent.

• 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).

• Meets the clinical criteria as defined by the Myasthenia Gravis Foundation of America (MGFA) class II, III, or IV

• Has an Myasthenia Gravis - Activities of Daily Living (MG-ADL) total score =5 at screening and the day 1 visit, with more than 50% of the score due to nonocular symptoms

• 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 screening.

• Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies and: Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before investigational medicinal product (IMP) can be administered.

Exclusion Criteria:

• Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening

• A positive test for SARS-CoV-2 at screening

• 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

• History of malignancy unless deemed cured by adequate treatment with no evidence of reoccurrence for =3 years before the first administration of the IMP. Participants with the following cancers can be included at any time, provided they are adequately treated at screening: 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)

• 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

• A thymectomy within 3 months of screening

• Pregnant or lactating females and those who intend to become pregnant during the study or within 90 days of the last dose of IMP

• Use of the following prior or concomitant therapies:

1. intravenous immunoglobulin (IVIg) or subcutaneous immunoglobulin (SCIg) within 14 days of day 1

2. Rituximab within 6 months of day 1

3. Eculizumab within 1 month of day 1

4. Other monoclonal antibodies (eg, adalimumab, tocilizumab, ixekizumab) within 5 half-lives of the monoclonal antibodies before day 1

5. Use of any other investigational product within 3 months or 5 half-lives, whichever is longer, before day 1

6. Receipt of a live or live-attenuated vaccines received within 4 weeks of screening. The receipt of any inactivated, subunit, polysaccharide, conjugate vaccine at any time before screening is not considered exclusionary.

• Previous participation in a clinical study or patient access program during which they were treated with efgartigimod

• Positive serum test at screening for an active viral infection with any of the following conditions: Hepatitis B virus (HBV) that is indictive of an acute or chronic infection; Hepatitis C virus (HCV) based on HCV antibody assay (unless associated with a negative HCV RNA test); HIV based on test results that are associated with an AIDS-defining condition or a CD4 count <200 cells/mm3

• Total IgG <6 g/L at screening

• Known hypersensitivity reaction to efgartigimod or any of its excipients

• The participant stands in any relationship of dependency with the sponsor.

• The participant has been institutionalized due to an official or judicial order.

Related Conditions & MeSH terms

• Generalized Myasthenia Gravis
• Muscle Weakness
• Myasthenia Gravis

Intervention

Biological:
• Efgartigimod concentrate for solution for infusion 20 mg/mL
Patients receiving efgartigimod IV treatment in a continuous treatment regimen
• Efgartigimod concentrate for solution for infusion 20 mg/mL
Patients receiving efgartigimod IV treatment in a cyclic treatment regimen

Locations

Country	Name	City	State
Austria	Investigator Site 26 - AT0430002	Innsbruck
Austria	Investigator Site 27 - AT0430001	Wien
Belgium	Investigator Site 28 - BE0320001	Leuven
Canada	Investigator Site 29 - CA0019003	London
Canada	Investigator site 37 - CA0019002	Québec
France	Investigator Site 23 - FR0330005	Bordeaux
France	Investigator Site 24 - FR0330004	Lille
France	Investigator Site 20 - FR0330001	Marseille
France	Investigator Site 25 - FR0330003	Nice
France	Investigator site 38 - FR0330002	Paris
Georgia	Investigator Site 1 - GEO9950001	Tbilisi
Georgia	Investigator Site 2 - GEO9950002	Tbilisi
Georgia	Investigator Site 3 - GEO9950003	Tbilisi
Germany	Investigator Site 33 - DE0490004	Berlin
Germany	Investigator Site 36 - DE0490002	Bochum
Germany	Investigator Site 32 - DE0490001	Essen
Germany	Investigator Site 34 - DE0490005	Hannover
Italy	Investigator Site 31 - IT0390005	Bologna
Italy	Investigator Site 30 - IT0390004	Genova
Italy	Investigator Site 21 - IT0390002	Milan
Italy	Investigator site 39 - IT0390006	Pisa
Italy	Investigator Site 22 - IT0390001	Roma
Netherlands	Investigator Site 35 - NL0310001	Amsterdam
Poland	Investigator Site 5 - PL0480002	Kraków
Poland	Investigator Site 4 - PL0480001	Lubin
Spain	Investigator Site 19 - ES0340001	Barcelona
Spain	Investigator Site 18 - ES0340002	Santiago De Compostela	A Coruña
United States	Investigator Site 16 - US0010009	Augusta	Georgia
United States	Investigator Site 11 - US0010011	Austin	Texas
United States	Investigator Site 9 - 0010006	Boca Raton	Florida
United States	Investigator Site 10 - US0010007	Carlsbad	California
United States	Investigator Site 8 - US0010003	Chicago	Illinois
United States	Investigator Site 15 - US0010014	Coral Springs	Florida
United States	Investigator Site 12 - US0010004	Kansas City	Kansas
United States	Investigator Site 6 - US0010008	Meadows	Illinois
United States	Investigator Site 7 - US0010001	Orange	California
United States	Investigator Site 17 - US0010012	Philadelphia	Pennsylvania
United States	Investigator Site 13 - US0010013	Portland	Oregon
United States	Investigator Site 14 - US0010010	Richmond	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
argenx

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  France,  Georgia,  Germany,  Italy,  Netherlands,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean of the average Myasthenia Gravis - Activities of Daily Living (MG-ADL) total score change from baseline during the visit of week (W)1 through W21 by regimen arm. A higher total score indicates more impairment.		21 weeks
Secondary	Incidence and severity of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESIs)		136 weeks
Secondary	Incidence of serious adverse events (SAEs) and AEs of special interest (AESIs)		136 weeks
Secondary	Change from baseline in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) total score over time. A higher total score indicates more impairment.		126 weeks
Secondary	Normalized area under the effect curve (AUEC) of MG-ADL total score improvement from baseline during following intervals: Day 1 through Week7, Week 7 through Week 14, Week 14 trough Week 21 and Week 7 through Week 21		21 weeks
Secondary	Characterization of MG-ADL total score change from baseline during the following 5 intervals using mean and standard deviation: Week 1 through Week 7, Week 8 through Week 14, Week 15 through Week 21, Week 8 through Week 21 and Week 1 through Week 21.		21 weeks
Secondary	Number 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 and W1 through W21.		21 weeks
Secondary	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 and W1 through W21.		21 weeks
Secondary	Percentage of time, participants have a change in MG-ADL total score of at least 2 points from baseline during Week 4 through Week 21.		21 weeks
Secondary	Number of participants who achieve minimal symptom expression (MSE), defined as a MG-ADL total score of 0 or 1		21 weeks
Secondary	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 though W7, W8 through W14, W15 through W21, W8 through W21 and W1 through W21.		21 weeks