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

Primary Purpose

Generalized Myasthenia Gravis

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Efgartigimod concentrate for solution for infusion 20 mg/mL
Efgartigimod concentrate for solution for infusion 20 mg/mL
Sponsored by
argenx
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Generalized Myasthenia Gravis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 (MFGA) 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 by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies and:

    a. Male participants:

  • Male participants are not allowed to donate sperm from signing the ICF until the end of the study.

    b. Female participants:

  • 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:

    1. Basal cell or squamous cell skin cancer
    2. Carcinoma in situ of the cervix
    3. Carcinoma in situ of the breast
    4. 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:

    1. Hepatitis B virus (HBV) that is indictive of an acute or chronic infection (https://www.cdc.gov/hepatitis/HBV/PDFs/SerologicChartv8.pdf)
    2. Hepatitis C virus (HCV) based on HCV antibody assay (unless associated with a negative HCV RNA test)
    3. 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.

Sites / Locations

  • Investigator Site 10 - US0010007
  • Investigator Site 7 - US0010001
  • Investigator Site 9 - 0010006
  • Investigator Site 15 - US0010014
  • Investigator Site 16 - US0010009
  • Investigator Site 8 - US0010003
  • Investigator Site 6 - US0010008
  • Investigator Site 12 - US0010004
  • Investigator Site 13 - US0010013
  • Investigator Site 17 - US0010012
  • Investigator Site 11 - US0010011
  • Investigator Site 14 - US0010010
  • Investigator Site 26 - AT0430002
  • Investigator Site 27 - AT0430001
  • Investigator Site 28 - BE0320001
  • Investigator Site 29 - CA0019003
  • Investigator site 37 - CA0019002
  • Investigator Site 23 - FR0330005
  • Investigator Site 24 - FR0330004
  • Investigator Site 20 - FR0330001
  • Investigator Site 25 - FR0330003
  • Investigator site 38 - FR0330002
  • Investigator Site 2 - GEO9950002
  • Investigator Site 1 - GEO9950001
  • Investigator Site 3 - GEO9950003
  • Investigator Site 33 - DE0490004
  • Investigator Site 36 - DE0490002
  • Investigator Site 32 - DE0490001
  • Investigator Site 34 - DE0490005
  • Investigator Site 31 - IT0390005
  • Investigator Site 30 - IT0390004
  • Investigator Site 21 - IT0390002
  • Investigator site 39 - IT0390006
  • Investigator Site 22 - IT0390001
  • Investigator Site 35 - NL0310001
  • Investigator Site 5 - PL0480002
  • Investigator Site 4 - PL0480001
  • Investigator Site 18 - ES0340002
  • Investigator Site 19 - ES0340001

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

efgartigimod IV - I

efgartigimod IV - II

Arm Description

Patients receiving efgartigimod IV treatment (Continuous regimen: efgartigimod 10 mg/kg q2w)

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Incidence and severity of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESIs)
Incidence of serious adverse events (SAEs) and AEs of special interest (AESIs)
Change from baseline in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) total score over time. A higher total score indicates more impairment.
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
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.
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.
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.
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.
Number of participants who achieve minimal symptom expression (MSE), defined as a MG-ADL total score of 0 or 1
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.

Full Information

First Posted
July 19, 2021
Last Updated
October 9, 2023
Sponsor
argenx
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1. Study Identification

Unique Protocol Identification Number
NCT04980495
Brief Title
An Open-label Study to Investigate the Clinical Efficacy of Different Dosing Regimens of Efgartigimod IV in Patients With Generalized Myasthenia Gravis
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 16, 2021 (Actual)
Primary Completion Date
August 24, 2023 (Actual)
Study Completion Date
November 3, 2025 (Anticipated)

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
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.

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
None (Open Label)
Allocation
Randomized
Enrollment
69 (Actual)

8. Arms, Groups, and Interventions

Arm Title
efgartigimod IV - I
Arm Type
Experimental
Arm Description
Patients receiving efgartigimod IV treatment (Continuous regimen: efgartigimod 10 mg/kg q2w)
Arm Title
efgartigimod IV - II
Arm Type
Experimental
Arm Description
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)
Intervention Type
Biological
Intervention Name(s)
Efgartigimod concentrate for solution for infusion 20 mg/mL
Other Intervention Name(s)
Efgartigimod IV
Intervention Description
Patients receiving efgartigimod IV treatment in a continuous treatment regimen
Intervention Type
Biological
Intervention Name(s)
Efgartigimod concentrate for solution for infusion 20 mg/mL
Other Intervention Name(s)
Efgartigimod IV
Intervention Description
Patients receiving efgartigimod IV treatment in a cyclic treatment regimen
Primary Outcome Measure Information:
Title
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.
Time Frame
21 weeks
Secondary Outcome Measure Information:
Title
Incidence and severity of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESIs)
Time Frame
136 weeks
Title
Incidence of serious adverse events (SAEs) and AEs of special interest (AESIs)
Time Frame
136 weeks
Title
Change from baseline in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) total score over time. A higher total score indicates more impairment.
Time Frame
126 weeks
Title
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
Time Frame
21 weeks
Title
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.
Time Frame
21 weeks
Title
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.
Time Frame
21 weeks
Title
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.
Time Frame
21 weeks
Title
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.
Time Frame
21 weeks
Title
Number of participants who achieve minimal symptom expression (MSE), defined as a MG-ADL total score of 0 or 1
Time Frame
21 weeks
Title
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.
Time Frame
21 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: intravenous immunoglobulin (IVIg) or subcutaneous immunoglobulin (SCIg) within 14 days of day 1 Rituximab within 6 months of day 1 Eculizumab within 1 month of day 1 Other monoclonal antibodies (eg, adalimumab, tocilizumab, ixekizumab) within 5 half-lives of the monoclonal antibodies before day 1 Use of any other investigational product within 3 months or 5 half-lives, whichever is longer, before day 1 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.
Facility Information:
Facility Name
Investigator Site 10 - US0010007
City
Carlsbad
State/Province
California
ZIP/Postal Code
92011
Country
United States
Facility Name
Investigator Site 7 - US0010001
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Investigator Site 9 - 0010006
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33487
Country
United States
Facility Name
Investigator Site 15 - US0010014
City
Coral Springs
State/Province
Florida
ZIP/Postal Code
33067
Country
United States
Facility Name
Investigator Site 16 - US0010009
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30910
Country
United States
Facility Name
Investigator Site 8 - US0010003
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Investigator Site 6 - US0010008
City
Meadows
State/Province
Illinois
ZIP/Postal Code
60008
Country
United States
Facility Name
Investigator Site 12 - US0010004
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Investigator Site 13 - US0010013
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Investigator Site 17 - US0010012
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Investigator Site 11 - US0010011
City
Austin
State/Province
Texas
ZIP/Postal Code
78756
Country
United States
Facility Name
Investigator Site 14 - US0010010
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23219
Country
United States
Facility Name
Investigator Site 26 - AT0430002
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
Facility Name
Investigator Site 27 - AT0430001
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Investigator Site 28 - BE0320001
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Investigator Site 29 - CA0019003
City
London
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
Investigator site 37 - CA0019002
City
Québec
ZIP/Postal Code
H3A 2B4
Country
Canada
Facility Name
Investigator Site 23 - FR0330005
City
Bordeaux
ZIP/Postal Code
33604
Country
France
Facility Name
Investigator Site 24 - FR0330004
City
Lille
ZIP/Postal Code
59000
Country
France
Facility Name
Investigator Site 20 - FR0330001
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
Investigator Site 25 - FR0330003
City
Nice
ZIP/Postal Code
06001
Country
France
Facility Name
Investigator site 38 - FR0330002
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Investigator Site 2 - GEO9950002
City
Tbilisi
ZIP/Postal Code
0112
Country
Georgia
Facility Name
Investigator Site 1 - GEO9950001
City
Tbilisi
ZIP/Postal Code
0114
Country
Georgia
Facility Name
Investigator Site 3 - GEO9950003
City
Tbilisi
ZIP/Postal Code
0114
Country
Georgia
Facility Name
Investigator Site 33 - DE0490004
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Investigator Site 36 - DE0490002
City
Bochum
ZIP/Postal Code
44791
Country
Germany
Facility Name
Investigator Site 32 - DE0490001
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Investigator Site 34 - DE0490005
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Investigator Site 31 - IT0390005
City
Bologna
ZIP/Postal Code
40139
Country
Italy
Facility Name
Investigator Site 30 - IT0390004
City
Genova
ZIP/Postal Code
16132
Country
Italy
Facility Name
Investigator Site 21 - IT0390002
City
Milan
ZIP/Postal Code
20133
Country
Italy
Facility Name
Investigator site 39 - IT0390006
City
Pisa
ZIP/Postal Code
56126
Country
Italy
Facility Name
Investigator Site 22 - IT0390001
City
Roma
ZIP/Postal Code
00168
Country
Italy
Facility Name
Investigator Site 35 - NL0310001
City
Amsterdam
ZIP/Postal Code
1105
Country
Netherlands
Facility Name
Investigator Site 5 - PL0480002
City
Kraków
ZIP/Postal Code
31-426
Country
Poland
Facility Name
Investigator Site 4 - PL0480001
City
Lubin
ZIP/Postal Code
20-093
Country
Poland
Facility Name
Investigator Site 18 - ES0340002
City
Santiago De Compostela
State/Province
A Coruña
ZIP/Postal Code
15706
Country
Spain
Facility Name
Investigator Site 19 - ES0340001
City
Barcelona
ZIP/Postal Code
08041
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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