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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Generalized Myasthenia Gravis
• Intervention / Treatment: Biological: Efgartigimod concentrate for solution for infusion 20 mg/mL; Biological: Efgartigimod concentrate for solution for infusion 20 mg/mL

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Investigator Site 26 - AT0430002
  • Wien, Austria, 1090
    • Investigator Site 27 - AT0430001
• Belgium
  • Leuven, Belgium, 3000
    • Investigator Site 28 - BE0320001
• Canada
  • London, Canada, N6A 5A5
    • Investigator Site 29 - CA0019003
  • Québec, Canada, H3A 2B4
    • Investigator site 37 - CA0019002
• France
  • Bordeaux, France, 33604
    • Investigator Site 23 - FR0330005
  • Lille, France, 59000
    • Investigator Site 24 - FR0330004
  • Marseille, France, 13385
    • Investigator Site 20 - FR0330001
  • Nice, France, 06001
    • Investigator Site 25 - FR0330003
  • Paris, France, 75013
    • Investigator site 38 - FR0330002
• Georgia
  • Tbilisi, Georgia, 0112
    • Investigator site 2 - GEO9950002
  • Tbilisi, Georgia, 0114
    • Investigator Site 1 - GEO9950001
  • Tbilisi, Georgia, 0114
    • Investigator site 3 - GEO9950003
• Germany
  • Berlin, Germany, 10117
    • Investigator Site 33 - DE0490004
  • Bochum, Germany, 44791
    • Investigator Site 36 - DE0490002
  • Essen, Germany, 45147
    • Investigator Site 32 - DE0490001
  • Hannover, Germany, 30625
    • Investigator Site 34 - DE0490005
• Italy
  • Bologna, Italy, 40139
    • Investigator Site 31 - IT0390005
  • Genova, Italy, 16132
    • Investigator Site 30 - IT0390004
  • Milan, Italy, 20133
    • Investigator Site 21 - IT0390002
  • Pisa, Italy, 56126
    • Investigator site 39 - IT0390006
  • Roma, Italy, 00168
    • Investigator Site 22 - IT0390001
• Netherlands
  • Amsterdam, Netherlands, 1105
    • Investigator Site 35 - NL0310001
• Poland
  • Kraków, Poland, 31-426
    • Investigator Site 5 - PL0480002
  • Lubin, Poland, 20-093
    • Investigator Site 4 - PL0480001
• Spain
  • Barcelona, Spain, 08041
    • Investigator Site 19 - ES0340001
  • A Coruña
    • Santiago De Compostela, A Coruña, Spain, 15706
      • Investigator Site 18 - ES0340002
• United States
  • California
    • Carlsbad, California, United States, 92011
      • Investigator Site 10 - US0010007
    • Orange, California, United States, 92868
      • Investigator Site 7 - US0010001
  • Florida
    • Boca Raton, Florida, United States, 33487
      • Investigator Site 9 - 0010006
    • Coral Springs, Florida, United States, 33067
      • Investigator Site 15 - US0010014
  • Georgia
    • Augusta, Georgia, United States, 30910
      • Investigator Site 16 - US0010009
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Investigator Site 8 - US0010003
    • Meadows, Illinois, United States, 60008
      • Investigator Site 6 - US0010008
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Investigator Site 12 - US0010004
  • Oregon
    • Portland, Oregon, United States, 97239
      • Investigator Site 13 - US0010013
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Investigator Site 17 - US0010012
  • Texas
    • Austin, Texas, United States, 78756
      • Investigator Site 11 - US0010011
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Investigator Site 14 - US0010010

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: efgartigimod IV - I; Patients receiving efgartigimod IV treatment (Continuous regimen: efgartigimod 10 mg/kg q2w)	Biological: Efgartigimod concentrate for solution for infusion 20 mg/mL; Patients receiving efgartigimod IV treatment in a continuous treatment regimen; Other Names: Efgartigimod IV; Biological: Efgartigimod concentrate for solution for infusion 20 mg/mL; Patients receiving efgartigimod IV treatment in a cyclic treatment regimen; Other Names: Efgartigimod IV
Experimental: efgartigimod IV - II; Patients receiving efgartigimod IV treatment (Cyclic regimen: efgartigimod 10 mg/kg q7d for a total of 4 infusions per TP for 2 TPs with a fixed 4-week IP between each TP)	Biological: Efgartigimod concentrate for solution for infusion 20 mg/mL; Patients receiving efgartigimod IV treatment in a continuous treatment regimen; Other Names: Efgartigimod IV; Biological: Efgartigimod concentrate for solution for infusion 20 mg/mL; Patients receiving efgartigimod IV treatment in a cyclic treatment regimen; Other Names: Efgartigimod IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
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
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
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
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
Number of participants who achieve minimal symptom expression (MSE), defined as a MG-ADL total score of 0 or 1	21 weeks
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
Incidence and severity of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESIs)	136 weeks
Incidence of serious adverse events (SAEs) and AEs of special interest (AESIs)	136 weeks
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

Collaborators and Investigators

• Sponsor: argenx

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2021
• Primary Completion (Actual): August 24, 2023
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: July 19, 2021
• First Submitted That Met QC Criteria: July 27, 2021
• First Posted (Actual): July 28, 2021

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis; Pharmaceutical Solutions
• Other Study ID Numbers: ARGX-113-2003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No