Back to resultsAn Efficacy and Safety Study of ARGX-113 in Patients With Myasthenia Gravis Who Have Generalized Muscle Weakness (ADAPT)
Primary Purpose
Generalized Myasthenia Gravis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ARGX-113
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Generalized Myasthenia Gravis
Eligibility Criteria
Inclusion Criteria:
- Patients with the ability to understand the requirements of the trial, provide written informed consent, and comply with the trial protocol procedures.
- Male or female patients aged ≥ 18 years.
- 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:
- Pregnant and lactating women, and those intending to become pregnant during the trial or within 90 days after the last dosing.
- 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.
- MGFA Class I and V patients.
- Patients with worsening muscle weakness secondary to concurrent infections or medications.
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.
Sites / Locations
- Investigator Site 29
- Investigator Site 66
- Investigator Site 5
- Investigator Site 49
- Investigator Site 18
- Investigator Site 40
- Investigator Site 59
- Investigator Site 58
- Investigator Site 34
- Investigator Site 4
- Investigator Site 30
- Investigator Site 25
- Investigator Site 21
- Investigator Site 27
- Investigator Site 48
- Investigator Site 53
- Investigator Site 3
- Investigator Site 20
- Investigator Site 9
- Investigator Site 17
- Investigator Site
- Investigator Site 44
- Investigator Site 6
- Investigator Site 2
- Investigator Site 16
- Investigator Site 11
- Investigator Site 8
- Investigator Site 38
- Investigator Site 24
- Investigator Site 22
- Investigator Site 32
- Investigator Site 35
- Investigator Site 51
- Investigator Site 36
- Investigator Site 15
- Investigator Site 13
- Investigator Site 52
- Investigator Site 46
- Investigator Site 45
- Investigator Site 47
- Investigator Site 33
- Investigator Site 55
- Investigator Site 54
- Investigator Site 10
- Investigator Site 12
- Investigator Site 42
- Investigator Site 26
- Investigator Site 19
- Investigator Site 43
- Investigator Site 50
- Investigator Site 28
- Investigator Site 31
- Investigator Site 41
- Investigator Site 39
- Investigator Site 37
- Investigator Site 7
- Investigator Site 57
- Investigator Site 14
- Investigator Site 23
- Investigator Site 64
- Investigator Site 62
- Investigator Site 65
- Investigator Site 60
- Investigator Site 61
- Investigator Site 63
- Investigator Site 56
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
ARGX-113
Placebo
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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).
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.
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03669588
Brief Title
An Efficacy and Safety Study of ARGX-113 in Patients With Myasthenia Gravis Who Have Generalized Muscle Weakness
Acronym
ADAPT
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
August 22, 2018 (Actual)
Primary Completion Date
April 6, 2020 (Actual)
Study Completion Date
April 6, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
argenx
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Generalized Myasthenia Gravis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
167 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ARGX-113
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Biological
Intervention Name(s)
ARGX-113
Other Intervention Name(s)
efgartigimod
Intervention Description
Intravenous administration of ARGX-113
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Intravenous administration of placebo
Primary Outcome Measure Information:
Title
Percentage of MG-ADL Responders During Cycle 1 (C1); Analyzed in the AChR-Ab Seropositive Population
Description
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.
Time Frame
Baseline up to Day 63 (end of TC1)
Secondary Outcome Measure Information:
Title
Percentage of Quantitative Myasthenia Gravis (QMG) Responders During C1; Analyzed in the AChR-Ab Seropositive Population
Description
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.
Time Frame
Baseline up to Day 63 (end of TC1)
Title
Percentage of MG-ADL Responders During C1; Analyzed in the Overall Population
Description
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.
Time Frame
Baseline up to Day 63 (end of TC1)
Title
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
Description
An MG-ADL CMI was defined as a reduction of ≥2 points on the total MG-ADL score compared to study entry baseline (SEB).
Time Frame
Baseline up to Day 126
Title
Time From Week 4 to Qualify for Retreatment; Analyzed in the AChR-Ab Seropositive Population
Description
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.
Time Frame
Week 4 up to Day 182 (end of study [EoS])
Title
Percentage of Early MG-ADL Responders During C1; Analyzed in the AChR-Ab Seropositive Population
Description
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).
Time Frame
Baseline up to Day 63 (end of TC1)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with the ability to understand the requirements of the trial, provide written informed consent, and comply with the trial protocol procedures.
Male or female patients aged ≥ 18 years.
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:
Pregnant and lactating women, and those intending to become pregnant during the trial or within 90 days after the last dosing.
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.
MGFA Class I and V patients.
Patients with worsening muscle weakness secondary to concurrent infections or medications.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonio Guglietta, MD
Organizational Affiliation
argenx
Official's Role
Study Director
Facility Information:
Facility Name
Investigator Site 29
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85018
Country
United States
Facility Name
Investigator Site 66
City
Carlsbad
State/Province
California
ZIP/Postal Code
92011
Country
United States
Facility Name
Investigator Site 5
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Investigator Site 49
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Investigator Site 18
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Investigator Site 40
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Investigator Site 59
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Investigator Site 58
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Investigator Site 34
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
Investigator Site 4
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Investigator Site 30
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62702
Country
United States
Facility Name
Investigator Site 25
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Investigator Site 21
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Investigator Site 27
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Investigator Site 48
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Investigator Site 53
City
Buffalo
State/Province
New York
ZIP/Postal Code
14202
Country
United States
Facility Name
Investigator Site 3
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Investigator Site 20
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Investigator Site 9
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Investigator Site 17
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Investigator Site
City
Cordova
State/Province
Tennessee
ZIP/Postal Code
38018
Country
United States
Facility Name
Investigator Site 44
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Investigator Site 6
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Investigator Site 2
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Investigator Site 16
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Facility Name
Investigator Site 11
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
Investigator Site 8
City
Ghent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Investigator Site 38
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2G3
Country
Canada
Facility Name
Investigator Site 24
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
Investigator Site 22
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H3A 2B4
Country
Canada
Facility Name
Investigator Site 32
City
Brno
ZIP/Postal Code
62500
Country
Czechia
Facility Name
Investigator Site 35
City
Ostrava-Poruba
ZIP/Postal Code
70852
Country
Czechia
Facility Name
Investigator Site 51
City
Praha 2
ZIP/Postal Code
128 00
Country
Czechia
Facility Name
Investigator Site 36
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark
Facility Name
Investigator Site 15
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Investigator Site 13
City
Bordeaux Cedex
ZIP/Postal Code
33076
Country
France
Facility Name
Investigator Site 52
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
Investigator Site 46
City
Tbilisi
ZIP/Postal Code
0112
Country
Georgia
Facility Name
Investigator Site 45
City
Tbilisi
ZIP/Postal Code
0114
Country
Georgia
Facility Name
Investigator Site 47
City
Tbilisi
ZIP/Postal Code
0114
Country
Georgia
Facility Name
Investigator Site 33
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Investigator Site 55
City
Budapest
ZIP/Postal Code
1204
Country
Hungary
Facility Name
Investigator Site 54
City
Szeged
ZIP/Postal Code
6725
Country
Hungary
Facility Name
Investigator Site 10
City
Milano
ZIP/Postal Code
20133
Country
Italy
Facility Name
Investigator Site 12
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Investigator Site 42
City
Chiba-shi
State/Province
Chiba
ZIP/Postal Code
260-8677
Country
Japan
Facility Name
Investigator Site 26
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
0608543
Country
Japan
Facility Name
Investigator Site 19
City
Hanamaki
State/Province
Iwate
ZIP/Postal Code
025-0075
Country
Japan
Facility Name
Investigator Site 43
City
Sendai
State/Province
Miyagi
ZIP/Postal Code
983-8520
Country
Japan
Facility Name
Investigator Site 50
City
Suita
State/Province
Osaka
ZIP/Postal Code
565-0871
Country
Japan
Facility Name
Investigator Site 28
City
Ōsaka-sayama
State/Province
Osaka
ZIP/Postal Code
5898511
Country
Japan
Facility Name
Investigator Site 31
City
Meguro
State/Province
Tokyo
ZIP/Postal Code
1538515
Country
Japan
Facility Name
Investigator Site 41
City
Minato-Ku
State/Province
Tokyo
ZIP/Postal Code
108-8329
Country
Japan
Facility Name
Investigator Site 39
City
Shinjuku-Ku
State/Province
Tokyo
ZIP/Postal Code
160-0023
Country
Japan
Facility Name
Investigator Site 37
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
Facility Name
Investigator Site 7
City
Gdańsk
ZIP/Postal Code
80-952
Country
Poland
Facility Name
Investigator Site 57
City
Katowice
ZIP/Postal Code
40-123
Country
Poland
Facility Name
Investigator Site 14
City
Kraków
ZIP/Postal Code
31-505
Country
Poland
Facility Name
Investigator Site 23
City
Warszawa
ZIP/Postal Code
02-097
Country
Poland
Facility Name
Investigator Site 64
City
Krasnoyarsk
ZIP/Postal Code
660037
Country
Russian Federation
Facility Name
Investigator Site 62
City
Nizhny Novgorod
ZIP/Postal Code
603126
Country
Russian Federation
Facility Name
Investigator Site 65
City
Novosibirsk
ZIP/Postal Code
630087
Country
Russian Federation
Facility Name
Investigator Site 60
City
Samara
ZIP/Postal Code
443095
Country
Russian Federation
Facility Name
Investigator Site 61
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Investigator Site 63
City
Edgbaston
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
Investigator Site 56
City
Liverpool
ZIP/Postal Code
L9 7LJ
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34146511
Citation
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.
Results Reference
derived
Learn more about this trial
An Efficacy and Safety Study of ARGX-113 in Patients With Myasthenia Gravis Who Have Generalized Muscle Weakness
We'll reach out to this number within 24 hrs