An Efficacy and Safety Study of ARGX-113 in Patients With Myasthenia Gravis Who Have Generalized Muscle Weakness (ADAPT)

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase 3 Trial to Evaluate the Efficacy, Safety and Tolerability of ARGX-113 in Patients With Myasthenia Gravis Having Generalized Muscle Weakness

A randomized, double-blind, placebo controlled, multicenter Phase 3 trial to evaluate the efficacy, safety, tolerability, quality of life and impact on normal daily activities of ARGX-113 in patients with gMG.

Study Overview

• Status: Completed
• Conditions: Generalized Myasthenia Gravis
• Intervention / Treatment: Biological: ARGX-113; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 167
• Phase: Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • Investigator Site 11
  • Ghent, Belgium, 9000
    • Investigator Site 8
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2G3
      • Investigator Site 38
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Investigator Site 24
  • Quebec
    • Montréal, Quebec, Canada, H3A 2B4
      • Investigator Site 22
• Czechia
  • Brno, Czechia, 62500
    • Investigator Site 32
  • Ostrava-Poruba, Czechia, 70852
    • Investigator Site 35
  • Praha 2, Czechia, 128 00
    • Investigator Site 51
• Denmark
  • Aarhus, Denmark, 8200
    • Investigator Site 36
  • Copenhagen, Denmark, 2100
    • Investigator Site 15
• France
  • Bordeaux Cedex, France, 33076
    • Investigator Site 13
  • Marseille, France, 13385
    • Investigator Site 52
• Georgia
  • Tbilisi, Georgia, 0112
    • Investigator Site 46
  • Tbilisi, Georgia, 0114
    • Investigator Site 45
  • Tbilisi, Georgia, 0114
    • Investigator Site 47
• Germany
  • Berlin, Germany, 10117
    • Investigator Site 33
• Hungary
  • Budapest, Hungary, 1204
    • Investigator Site 55
  • Szeged, Hungary, 6725
    • Investigator Site 54
• Italy
  • Milano, Italy, 20133
    • Investigator Site 10
  • Napoli, Italy, 80131
    • Investigator Site 12
• Japan
  • Chiba
    • Chiba-shi, Chiba, Japan, 260-8677
      • Investigator Site 42
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 0608543
      • Investigator Site 26
  • Iwate
    • Hanamaki, Iwate, Japan, 025-0075
      • Investigator Site 19
  • Miyagi
    • Sendai, Miyagi, Japan, 983-8520
      • Investigator Site 43
  • Osaka
    • Suita, Osaka, Japan, 565-0871
      • Investigator Site 50
    • Ōsaka-sayama, Osaka, Japan, 5898511
      • Investigator Site 28
  • Tokyo
    • Meguro, Tokyo, Japan, 1538515
      • Investigator Site 31
    • Minato-Ku, Tokyo, Japan, 108-8329
      • Investigator Site 41
    • Shinjuku-Ku, Tokyo, Japan, 160-0023
      • Investigator Site 39
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Investigator Site 37
• Poland
  • Gdańsk, Poland, 80-952
    • Investigator Site 7
  • Katowice, Poland, 40-123
    • Investigator Site 57
  • Kraków, Poland, 31-505
    • Investigator Site 14
  • Warszawa, Poland, 02-097
    • Investigator Site 23
• Russian Federation
  • Krasnoyarsk, Russian Federation, 660037
    • Investigator Site 64
  • Nizhny Novgorod, Russian Federation, 603126
    • Investigator Site 62
  • Novosibirsk, Russian Federation, 630087
    • Investigator Site 65
  • Samara, Russian Federation, 443095
    • Investigator Site 60
• Serbia
  • Belgrade, Serbia, 11000
    • Investigator Site 61
• United Kingdom
  • Edgbaston, United Kingdom, B15 2TH
    • Investigator Site 63
  • Liverpool, United Kingdom, L9 7LJ
    • Investigator Site 56
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Investigator Site 29
  • California
    • Carlsbad, California, United States, 92011
      • Investigator Site 66
    • Los Angeles, California, United States, 90033
      • Investigator Site 5
    • Los Angeles, California, United States, 90095
      • Investigator Site 49
    • Orange, California, United States, 92868
      • Investigator Site 18
    • Palo Alto, California, United States, 94304
      • Investigator Site 40
    • San Francisco, California, United States, 94115
      • Investigator Site 59
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Investigator Site 58
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Investigator Site 34
    • Tampa, Florida, United States, 33612
      • Investigator Site 4
  • Illinois
    • Springfield, Illinois, United States, 62702
      • Investigator Site 30
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Investigator Site 25
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Investigator Site 21
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Investigator Site 27
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Investigator Site 48
  • New York
    • Buffalo, New York, United States, 14202
      • Investigator Site 53
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Investigator Site 3
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Investigator Site 20
  • Oregon
    • Portland, Oregon, United States, 97239
      • Investigator Site 9
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Investigator Site 17
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Investigator site
  • Texas
    • Houston, Texas, United States, 77030
      • Investigator Site 44
    • San Antonio, Texas, United States, 78229
      • Investigator Site 6
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Investigator Site 2
  • Washington
    • Seattle, Washington, United States, 98195
      • Investigator Site 16

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with the ability to understand the requirements of the trial, provide written informed consent, and comply with the trial protocol procedures.
2. Male or female patients aged ≥ 18 years.
3. Diagnosis of MG with generalized muscle weakness meeting the clinical criteria for diagnosis of MG as defined by the Myasthenia Gravis Foundation of America (MGFA) class II, III, IVa and IVb.

Other, more specific inclusion criteria are defined in the protocol

Exclusion Criteria:

1. Pregnant and lactating women, and those intending to become pregnant during the trial or within 90 days after the last dosing.
2. Male patients who are sexually active and do not intend to use effective methods of contraception during the trial or within 90 days after the last dosing or male patients who plan to donate sperm during the trial or within 90 days after the last dosing.
3. MGFA Class I and V patients.
4. Patients with worsening muscle weakness secondary to concurrent infections or medications.

5. Patients with known seropositivity or who test positive for an active viral infection at Screening with:

   • Hepatitis B Virus (HBV) (except patients who are seropositive because of HBV vaccination)
   • Hepatitis C Virus (HCV)
   • Human Immunodeficiency Virus (HIV)

Other, more specific exclusion criteria are further defined in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Biological: Placebo; Intravenous administration of placebo
Experimental: ARGX-113	Biological: ARGX-113; Intravenous administration of ARGX-113; Other Names: efgartigimod

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of MG-ADL Responders During Cycle 1 (C1); Analyzed in the AChR-Ab Seropositive Population	The MG-ADL is an 8-item patient-reported scale to assess MG symptoms and their effects on daily activities. The scale comprises 2 items on daily life activities and 6 items on symptoms. The MG-ADL total score range is 0-24, with higher scores indicative of greater disease severity. A patient was considered an MG-ADL responder during C1 if there was a reduction of ≥2 points on the MG-ADL total score (compared to baseline of C1 [C1B]) for ≥4 consecutive weeks with the first reduction occurring no later than 1 week after the last infusion of IMP in C1.	Baseline up to Day 63 (end of TC1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Quantitative Myasthenia Gravis (QMG) Responders During C1; Analyzed in the AChR-Ab Seropositive Population	The QMG scale quantifies disease severity based on impairments of body functions and structures as defined by the International Classification of Disability and Health. The QMG scale consists of 13 items that measure endurance or fatigability, and accounts for fluctuations in disease state. The QMG total score range is 0-39, with higher scores indicative of greater disease severity. A patient was considered a QMG responder during C1 if there was a reduction of ≥3-points on the QMG total score (compared to C1B) for ≥4 consecutive weeks with the first reduction occurring no later than 1 week after the last infusion of IMP in C1.	Baseline up to Day 63 (end of TC1)
Percentage of MG-ADL Responders During C1; Analyzed in the Overall Population	The percentage of MG-ADL responders during C1 in the overall population is reported for this secondary end point; percentage of MG-ADL responders during C1 in the AChR-Ab seropositive population is reported previously as a primary end point.	Baseline up to Day 63 (end of TC1)
Percentage of Time That Patients Had a Clinically Meaningful Improvement (CMI) in MG-ADL Total Score up to and Including Day 126; Analyzed in the AChR-Ab Seropositive Population	An MG-ADL CMI was defined as a reduction of ≥2 points on the total MG-ADL score compared to study entry baseline (SEB).	Baseline up to Day 126
Time From Week 4 to Qualify for Retreatment; Analyzed in the AChR-Ab Seropositive Population	Time to qualify for retreatment was defined as time from the Week 4 assessment until the first visit with a <2-point reduction compared to SEB in the MG-ADL total score and MG-ADL total score ≥5 points with >50% of the total score attributable to nonocular symptoms.	Week 4 up to Day 182 (end of study [EoS])
Percentage of Early MG-ADL Responders During C1; Analyzed in the AChR-Ab Seropositive Population	A patient was considered an early MG-ADL responder during C1 if there was a reduction of ≥2 points on the MG-ADL total score (compared to C1B) for ≥4 consecutive weeks with the first reduction occurring no later than Week 2 (ie, after 1 or maximum 2 infusions of IMP in C1).	Baseline up to Day 63 (end of TC1)

Collaborators and Investigators

• Sponsor: argenx
• Investigators: Study Director: Antonio Guglietta, MD, argenx

Publications and helpful links

General Publications

• Howard JF Jr, Bril V, Vu T, Karam C, Peric S, Margania T, Murai H, Bilinska M, Shakarishvili R, Smilowski M, Guglietta A, Ulrichts P, Vangeneugden T, Utsugisawa K, Verschuuren J, Mantegazza R; ADAPT Investigator Study Group. Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2021 Jul;20(7):526-536. doi: 10.1016/S1474-4422(21)00159-9. Erratum In: Lancet Neurol. 2021 Aug;20(8):e5.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2018
• Primary Completion (Actual): April 6, 2020
• Study Completion (Actual): April 6, 2020

Study Registration Dates

• First Submitted: September 6, 2018
• First Submitted That Met QC Criteria: September 11, 2018
• First Posted (Actual): September 13, 2018

Study Record Updates

• Last Update Posted (Actual): February 8, 2022
• Last Update Submitted That Met QC Criteria: January 14, 2022
• Last Verified: March 1, 2021

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; Paresis
• Other Study ID Numbers: ARGX-113-1704; 2018-002132-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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