Clinical trial NCT04735432: Evaluating the Pharmacodynamic Noninferiority of Efgartigimod PH20 SC Administered Subcutaneously as Compared to Efgartigimod Administered Intravenously in Patients With Generalized Myasthenia Gravis
Official title: A Phase 3, Randomized, Open-Label, Parallel-Group Study to Compare the Pharmacodynamics, Pharmacokinetics, Efficacy, Safety, Tolerability, and Immunogenicity of Multiple Subcutaneous Injections of Efgartigimod PH20 SC With Multiple Intravenous Infusions of Efgartigimod in Patients With Generalized Myasthenia Gravis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Generalized Myasthenia Gravis
Lead sponsor: argenx
Sponsor class: INDUSTRY
First posted: 2021-02-03
Enrollment: 110
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 study is to investigate the Pharmacodynamics (PD), Pharmacokinetics (PK), safety, tolerability, immunogenicity, and clinical efficacy of efgartigimod coformulated with recombinant human hyaluronidase PH20 (rHuPH20) as compared to efgartigimod IV infused in patients with generalized myasthenia gravis (gMG). The study duration is approximately 12 weeks. After screening, patients will be randomized to receive either efgartigimod infusions or efgartigimod PH20 subcutaneously (SC)

Detailed description: Main objective of the trial: To demonstrate that the pharmacodynamic (PD) effect of injections of 1000 mg efgartigimod PH20 SC (efgartigimod co-formulated with recombinant humanhyaluronidase PH20 for subcutaneous administration), administered once weekly for 4 administrations, is NI (noninferior) to IV infusions of efgartigimod (efgartigimod formulation for intravenous infusion) at a dose of 10 mg/kg administered once weekly for 4 administrations.

Secondary objectives: To compare the PD effect of efgartigimod PH20 SC and efgartigimod IV over time; To evaluate the pharmacokinetics (PK) of efgartigimod PH20 SC and efgartigimod IV; To evaluate the safety, tolerability, and immunogenicity of efgartigimod PH20 SC and efgartigimod IV; To evaluate the clinical efficacy of efgartigimod PH20 SC and efgartigimod IV.

Eligibility criteria: Inclusion Criteria:

Bullet list of each inclusion criterium:

1. Must be 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.
2. At least 18 years of age at the time of signing the informed consent form.
3. Diagnosed with generalized Myasthenia Gravis (gMG) with confirmed documentation and supported by at least 1 of the following:

   1. History of abnormal neuromuscular transmission demonstrated by single fiber electromyography or repetitive nerve stimulation
   2. History of positive edrophonium chloride test
   3. Demonstrated improvement in Myasthenia Gravis (MG) signs upon treatment with oral acetylcholinesterase (AChE) inhibitors as assessed by the treating physician
4. Meeting the clinical criteria as defined by the Myasthenia Gravis Foundation of America (MGFA) class II, III, IVa, or IVb

Exclusion Criteria:

Bullet list of each exclusion criterium:

1. Are pregnant or lactating, or intend to become pregnant during the study or within 90 days after the last dose of Investigational Medicinal Product.
2. Has any of the following medical conditions:

   1. Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening
   2. Any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of clinical symptoms of myasthenia gravis or put the participant at undue risk.
   3. 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:

      * adequately treated basal cell or squamous cell skin cancer
      * carcinoma in situ of the cervix
      * carcinoma in situ of the breast
      * incidental histological findings of prostate cancer (TNM Classification of Malignant Tumors stage T1a or T1b).
   4. Clinical evidence of other significant serious diseases, or the participant has had a recent major surgery, or who have any other condition that, in the opinion of the investigator, could confound the results of the study or put the participant at undue risk.

Primary outcomes:
measure: Percent Change From Baseline in Total IgG Levels at Day 29 (mITT Analysis Set)
timeFrame: From week 0 to week 4
Secondary outcomes:
measure: Percent Change From Baseline in Total IgG Levels Over Time (mITT Analysis Set)
timeFrame: From baseline to week 10
measure: Percent Change From Baseline in AChR-Ab Levels Over Time in AChR- Ab Positive Patients (mITT Analysis Set)
timeFrame: From baseline to week 10
measure: Percent Change From Baseline in IgG Subtype Levels Over Time (mITT Analysis Set)
timeFrame: Baseline to week 10
measure: AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set)
timeFrame: From baseline to week 10
measure: Еfgartigimod IV and PH20 SC Serum Pharmacokinetic Parameter Ctrough
timeFrame: From Week 1 to Week 4.
measure: Efgartigimod IV Serum Pharmacokinetic Parameter Cmax
timeFrame: From Baseline to Week 3
measure: Incidence of ADA Against Efgartigimod (Safety Analysis Set)
timeFrame: From baseline to week 10
measure: Incidence of Antibodies Against rHuPH20 in the SC Treatment Arm (Safety Analysis Set)
timeFrame: From baseline to week 10
measure: Incidence and Severity of AEs and SAEs (Safety Analysis Set)
timeFrame: From baseline to week 10
measure: MG-ADL Responders (ITT Analysis Set)
timeFrame: From baseline to week 10
measure: QMG Responders (ITT Analysis Set)
timeFrame: From Baseline to Week 10
measure: Change From Baseline in MG-ADL Total Score Over Time (ITT Analysis Set)
timeFrame: From baseline to week 10
measure: Change From Baseline in QMG Score Over Time (ITT Analysis Set)
timeFrame: From baseline to week 10
Other outcomes:
Locations:
city: Carlsbad
country: United States
facility: Investigator site 2 - US0010032
state: California
city: Orange
country: United States
facility: Investigator Site 41 - US0010004
state: California
city: Boca Raton
country: United States
facility: Investigator site 2 - US0010108
state: Florida
city: Port Charlotte
country: United States
facility: Investigator site 1 - US0010110
state: Florida
city: Tampa
country: United States
facility: Investigator Site 27 - US0010006
state: Florida
city: Augusta
country: United States
facility: Investigator Site 47 - US0010113
state: Georgia
city: Kansas City
country: United States
facility: Investigator Site 42 - US0010015
state: Kansas
city: Amherst
country: United States
facility: Investigator Site 11 - US0010111
state: New York
city: Chapel Hill
country: United States
facility: Investigator Site 40 - US0010003
state: North Carolina
city: Durham
country: United States
facility: Investigator Site 38 - US0010077
state: North Carolina
city: Cleveland
country: United States
facility: Investigator Site 43 - 0010019
state: Ohio
city: Cordova
country: United States
facility: Investigator site 4 - US0010008
state: Tennessee
city: Austin
country: United States
facility: Investigator Site 28 - US0010066
state: Texas
city: Texas City
country: United States
facility: Investigator Site 46 - US0010009
state: Texas
city: Gent
country: Belgium
facility: Investigator site 5 - BE0320007
state: East-Flanders
city: Tbilisi
country: Georgia
facility: Investigator site 13 - GE9950002
city: Tbilisi
country: Georgia
facility: Investigator site 12 - GE9950001
city: Tbilisi
country: Georgia
facility: Investigator site 14 - GE9950003
city: Tbilisi
country: Georgia
facility: Investigator Site 44 - GE9950004
city: Tbilisi
country: Georgia
facility: Investigator Site 45 - GE9950016
city: Berlin
country: Germany
facility: Investigator Site 30 - DE490006
city: Münster
country: Germany
facility: Investigator Site 29 - DE490009
city: Budapest
country: Hungary
facility: Investigator site 15 - HU0360013
city: Debrecen
country: Hungary
facility: Investigator Site 16 - HU0360020
city: Milan
country: Italy
facility: Investigator Site 17 - IT0390003
city: Roma
country: Italy
facility: Investigator Site 39 - IT0390008
city: Sapporo
country: Japan
facility: Investigator Site 31 - JP0810055
state: Hokkaido
city: Chiba
country: Japan
facility: Investigator Site 18 - JP0810002
city: Hanamaki
country: Japan
facility: Investigator site 6 - JPN0810004
city: Hiroshima
country: Japan
facility: Investigator Site 33 - JP0810058
city: Osaka
country: Japan
facility: Investigator Site 19 - JP0810007
city: Sendai
country: Japan
facility: Investigator Site 34 - JP0810005
city: Tokyo
country: Japan
facility: Investigator Site 32 - JP0810059
city: Tokyo
country: Japan
facility: Investigator Site 20 - JP0810009
city: Leiden
country: Netherlands
facility: Investigator Site 7 - NL0310001
city: Gdańsk
country: Poland
facility: Investigator Site 21 - PL0480001
city: Katowice
country: Poland
facility: Investigator Site 8 - PL0480007
city: Kraków
country: Poland
facility: Investigator Site 9 - PL0480024
city: Kraków
country: Poland
facility: Investigator Site 22 - PL0480005
city: Lublin
country: Poland
facility: Investigator Site 23 - PL0480018
city: Warsaw
country: Poland
facility: Investigator Site 24 - PL0480022
city: Novosibirsk
country: Russian Federation
facility: Investigator Site 35 - RU0070002
city: Saint Petersburg
country: Russian Federation
facility: Investigator Site 36 - RU0070014
city: Barcelona
country: Spain
facility: Investigator Site 37 - ES0340021
city: Barcelona
country: Spain
facility: Investigator Site 26 - ES0340038
city: Madrid
country: Spain
facility: Investigator Site 25 - ES0340002
city: Valencia
country: Spain
facility: Investigator Site 10 - ES0340039
Study officials:
References: