Clinical trial NCT04980495: An Open-label Study to Investigate the Clinical Efficacy of Different Dosing Regimens of Efgartigimod IV in Patients With Generalized Myasthenia Gravis
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Generalized Myasthenia Gravis
Lead sponsor: argenx
Sponsor class: INDUSTRY
First posted: 2021-07-28
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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:

  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.

Primary outcomes:
measure: 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.
timeFrame: 21 weeks
Secondary outcomes:
measure: Incidence and severity of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESIs)
timeFrame: 136 weeks
measure: Incidence of serious adverse events (SAEs) and AEs of special interest (AESIs)
timeFrame: 136 weeks
measure: Change from baseline in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) total score over time. A higher total score indicates more impairment.
timeFrame: 126 weeks
measure: 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
timeFrame: 21 weeks
measure: 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.
timeFrame: 21 weeks
measure: 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.
timeFrame: 21 weeks
measure: 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.
timeFrame: 21 weeks
measure: 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.
timeFrame: 21 weeks
measure: Number of participants who achieve minimal symptom expression (MSE), defined as a MG-ADL total score of 0 or 1
timeFrame: 21 weeks
measure: 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.
timeFrame: 21 weeks
Other outcomes:
Locations:
city: Carlsbad
country: United States
facility: Investigator Site 10 - US0010007
state: California
city: Orange
country: United States
facility: Investigator Site 7 - US0010001
state: California
city: Boca Raton
country: United States
facility: Investigator Site 9 - 0010006
state: Florida
city: Coral Springs
country: United States
facility: Investigator Site 15 - US0010014
state: Florida
city: Augusta
country: United States
facility: Investigator Site 16 - US0010009
state: Georgia
city: Chicago
country: United States
facility: Investigator Site 8 - US0010003
state: Illinois
city: Meadows
country: United States
facility: Investigator Site 6 - US0010008
state: Illinois
city: Kansas City
country: United States
facility: Investigator Site 12 - US0010004
state: Kansas
city: Portland
country: United States
facility: Investigator Site 13 - US0010013
state: Oregon
city: Philadelphia
country: United States
facility: Investigator Site 17 - US0010012
state: Pennsylvania
city: Austin
country: United States
facility: Investigator Site 11 - US0010011
state: Texas
city: Richmond
country: United States
facility: Investigator Site 14 - US0010010
state: Virginia
city: Innsbruck
country: Austria
facility: Investigator Site 26 - AT0430002
city: Wien
country: Austria
facility: Investigator Site 27 - AT0430001
city: Leuven
country: Belgium
facility: Investigator Site 28 - BE0320001
city: London
country: Canada
facility: Investigator Site 29 - CA0019003
city: Québec
country: Canada
facility: Investigator site 37 - CA0019002
city: Bordeaux
country: France
facility: Investigator Site 23 - FR0330005
city: Lille
country: France
facility: Investigator Site 24 - FR0330004
city: Marseille
country: France
facility: Investigator Site 20 - FR0330001
city: Nice
country: France
facility: Investigator Site 25 - FR0330003
city: Paris
country: France
facility: Investigator site 38 - FR0330002
city: Tbilisi
country: Georgia
facility: Investigator Site 2 - GEO9950002
city: Tbilisi
country: Georgia
facility: Investigator Site 1 - GEO9950001
city: Tbilisi
country: Georgia
facility: Investigator Site 3 - GEO9950003
city: Berlin
country: Germany
facility: Investigator Site 33 - DE0490004
city: Bochum
country: Germany
facility: Investigator Site 36 - DE0490002
city: Essen
country: Germany
facility: Investigator Site 32 - DE0490001
city: Hannover
country: Germany
facility: Investigator Site 34 - DE0490005
city: Bologna
country: Italy
facility: Investigator Site 31 - IT0390005
city: Genova
country: Italy
facility: Investigator Site 30 - IT0390004
city: Milan
country: Italy
facility: Investigator Site 21 - IT0390002
city: Pisa
country: Italy
facility: Investigator site 39 - IT0390006
city: Roma
country: Italy
facility: Investigator Site 22 - IT0390001
city: Amsterdam
country: Netherlands
facility: Investigator Site 35 - NL0310001
city: Kraków
country: Poland
facility: Investigator Site 5 - PL0480002
city: Lubin
country: Poland
facility: Investigator Site 4 - PL0480001
city: Santiago De Compostela
country: Spain
facility: Investigator Site 18 - ES0340002
state: A Coruña
city: Barcelona
country: Spain
facility: Investigator Site 19 - ES0340001
Study officials:
References: