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

Phase 3
Completed
Conditions
Generalized Myasthenia Gravis
Interventions
Biological: Placebo
Biological: ARGX-113
Registration Number
NCT03669588
Lead Sponsor
argenx
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
167
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo-
ARGX-113ARGX-113-
Primary Outcome Measures
NameTimeMethod
Percentage of MG-ADL Responders During Cycle 1 (C1); Analyzed in the AChR-Ab Seropositive PopulationBaseline up to Day 63 (end of TC1)

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
NameTimeMethod
Percentage of Quantitative Myasthenia Gravis (QMG) Responders During C1; Analyzed in the AChR-Ab Seropositive PopulationBaseline up to Day 63 (end of TC1)

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 PopulationBaseline up to Day 63 (end of TC1)

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 PopulationBaseline up to Day 126

An MG-ADL CMI was defined as a reduction of ≥2 points on the total MG-ADL score compared to study entry baseline (SEB).

Percentage of Early MG-ADL Responders During C1; Analyzed in the AChR-Ab Seropositive PopulationBaseline up to Day 63 (end of TC1)

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 From Week 4 to Qualify for Retreatment; Analyzed in the AChR-Ab Seropositive PopulationWeek 4 up to Day 182 (end of study [EoS])

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.

Trial Locations

Locations (66)

Investigator Site 8

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Ghent, Belgium

Investigator Site 57

🇵🇱

Katowice, Poland

Investigator Site 41

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Minato-Ku, Tokyo, Japan

Investigator Site 7

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Gdańsk, Poland

Investigator Site 14

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Kraków, Poland

Investigator Site 62

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Nizhny Novgorod, Russian Federation

Investigator Site 5

🇺🇸

Los Angeles, California, United States

Investigator Site 20

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Cleveland, Ohio, United States

Investigator Site 27

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Boston, Massachusetts, United States

Investigator Site 6

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San Antonio, Texas, United States

Investigator Site

🇺🇸

Cordova, Tennessee, United States

Investigator Site 11

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Edegem, Belgium

Investigator Site 46

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Tbilisi, Georgia

Investigator Site 47

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Tbilisi, Georgia

Investigator Site 53

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Buffalo, New York, United States

Investigator Site 30

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Springfield, Illinois, United States

Investigator Site 4

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Tampa, Florida, United States

Investigator Site 40

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Palo Alto, California, United States

Investigator Site 32

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Brno, Czechia

Investigator Site 22

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Montréal, Quebec, Canada

Investigator Site 49

🇺🇸

Los Angeles, California, United States

Investigator Site 38

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Edmonton, Alberta, Canada

Investigator Site 19

🇯🇵

Hanamaki, Iwate, Japan

Investigator Site 52

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Marseille, France

Investigator Site 66

🇺🇸

Carlsbad, California, United States

Investigator Site 17

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Charleston, South Carolina, United States

Investigator Site 45

🇬🇪

Tbilisi, Georgia

Investigator Site 54

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Szeged, Hungary

Investigator Site 64

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Krasnoyarsk, Russian Federation

Investigator Site 13

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Bordeaux Cedex, France

Investigator Site 56

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Liverpool, United Kingdom

Investigator Site 48

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Detroit, Michigan, United States

Investigator Site 55

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Budapest, Hungary

Investigator Site 26

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Sapporo, Hokkaido, Japan

Investigator Site 23

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Warszawa, Poland

Investigator Site 10

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Milano, Italy

Investigator Site 36

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Aarhus, Denmark

Investigator Site 65

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Novosibirsk, Russian Federation

Investigator Site 60

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Samara, Russian Federation

Investigator Site 61

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Belgrade, Serbia

Investigator Site 51

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Praha 2, Czechia

Investigator Site 15

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Copenhagen, Denmark

Investigator Site 3

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Chapel Hill, North Carolina, United States

Investigator Site 35

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Ostrava-Poruba, Czechia

Investigator Site 43

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Sendai, Miyagi, Japan

Investigator Site 28

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Ōsaka-sayama, Osaka, Japan

Investigator Site 31

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Meguro, Tokyo, Japan

Investigator Site 12

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Napoli, Italy

Investigator Site 24

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Toronto, Ontario, Canada

Investigator Site 33

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Berlin, Germany

Investigator Site 42

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Chiba-shi, Chiba, Japan

Investigator Site 50

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Suita, Osaka, Japan

Investigator Site 63

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Edgbaston, United Kingdom

Investigator Site 29

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Phoenix, Arizona, United States

Investigator Site 59

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San Francisco, California, United States

Investigator Site 58

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Aurora, Colorado, United States

Investigator Site 34

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Jacksonville, Florida, United States

Investigator Site 25

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Iowa City, Iowa, United States

Investigator Site 21

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Kansas City, Kansas, United States

Investigator Site 9

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Portland, Oregon, United States

Investigator Site 2

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Charlottesville, Virginia, United States

Investigator Site 44

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Houston, Texas, United States

Investigator Site 16

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Seattle, Washington, United States

Investigator Site 37

🇳🇱

Leiden, Netherlands

Investigator Site 39

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Shinjuku-Ku, Tokyo, Japan

Investigator Site 18

🇺🇸

Orange, California, United States

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