Evaluating the Long-Term Safety and Tolerability of Efgartigimod PH20 SC Administered Subcutaneously in Patients With Generalized Myasthenia Gravis (ADAPTSC+)

A Long-Term, Single-Arm, Open-label, Multicenter Phase 3 Study to Evaluate the Safety and Tolerability of Multiple Subcutaneous Injections of Efgartigimod PH20 SC in Patients With Generalized Myasthenia Gravis

The purpose of this study is to evaluate the long-term safety and tolerability of efgartigimod PH20 SC 1000 mg, and the clinical efficacy, PD, pharmacokinetics (PK), immunogenicity, impact on the quality of life (QoL) of the participants, treatment satisfaction, and administration method preference, and the feasibility of self- and caregiver-supported administration of the SC injection.

Treatment duration: 3-week treatment periods, repeated as needed with at least 28 days in between treatment periods

Health measurements: total levels of immunoglobulin G (IgG), Acetylcholine receptor binding autoantibodies (AChR-Ab) levels, Myasthenia Gravis Activities of Daly Living (MG-ADL).

Study Overview

• Status: Active, not recruiting
• Conditions: Generalized Myasthenia Gravis
• Intervention / Treatment: Biological: efgartigimod PH20 SC

• Study Type: Interventional
• Enrollment (Actual): 183
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Investigator site 5 - BE0320007
• Czechia
  • Brno, Czechia, 625 00
    • Investigator site 24 - CZ4200005
• Georgia
  • Tbilisi, Georgia, 0112
    • Investigator site 2 - GEO9950002
  • Tbilisi, Georgia, 0114
    • Investigator Site 1 - GEO9950001
  • Tbilisi, Georgia, 0114
    • Investigator site 3 - GEO9950003
  • Tbilisi, Georgia, 0160
    • Investigator Site 32 - GEO9950004
  • Tbilisi, Georgia, 016
    • Investigator Site 33 - GEO9950016
• Germany
  • Berlin, Germany, 10117
    • Investigator Site 25 - DE490006
  • Münster, Germany, 48149
    • Investigator Site 26 - DE490009
• Hungary
  • Budapest, Hungary, 1082
    • Investigator site 10 - HU0360013
  • Budapest, Hungary, 1204
    • Investigator site 9 - HU0360012
• Italy
  • Milano, Italy, 20133
    • Investigator site 11 - IT0390003
  • Napoli, Italy, 80138
    • Investigator Site 34 - IT0390007
  • Roma, Italy, 00189
    • Investigator Site 35 - IT0390008
• Japan
  • Osaka, Japan, 565-0871
    • Investigator site 14 - JP0810007
  • Sapporo, Japan, 060 8542
    • Investigator Site 27 - JP0810008
  • Sendai-shi, Japan, 983-8520
    • Investigator site 13 - JP0810005
  • Tokyo, Japan, 160-0023
    • Investigator site 15 - JP0810009
  • Chiba-Shi
    • Chiba, Chiba-Shi, Japan, 260-8677
      • Investigator site 12 - JP0810002
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 063-0005
      • Investigator Site 36 - JP0810055
  • Iwate
    • Hanamaki, Iwate, Japan, 025-0082
      • Investigator site 8 - JP0810004
  • Tokyo
    • Ota-Ku, Tokyo, Japan, 143-8541
      • Investigator Site 28- JP0810059
• Netherlands
  • Leiden, Netherlands, 2333
    • Investigator site 16 - NL0310001
• Poland
  • Gdańsk, Poland, 80-952
    • Investigator site 17 - PL0480001
  • Katowice, Poland, 40-123
    • Investigator site 19 - PL0480007
  • Kraków, Poland, 31-505
    • Investigator site 18 - PL0480005
  • Kraków, Poland, 31-426
    • Investigator site 22 - PL0480065
  • Lublin, Poland, 20-093
    • Investigator site 20 - PL0480018
  • Warsaw, Poland, 02-097
    • Investigator site 21 - PL0480022
• Russian Federation
  • Novosibirsk, Russian Federation, 630087
    • Investigator Site 29- RU0070002
  • Saint Petersburg, Russian Federation, 194354
    • Investigator Site 30 - RU0070014
• Spain
  • Barcelona, Spain, 08035
    • Investigator Site 37 - ES0340021
  • Barcelona, Spain, 08041
    • Investigator Site 31 - ES0340038
  • Valencia, Spain, 46026
    • Investigator site 23 - ES0340039
• United States
  • California
    • Carlsbad, California, United States, 92011
      • Investigator site 6 - US0010032
    • Palo Alto, California, United States, 94304
      • Investigator Site 47 - US0010021
  • Florida
    • Boca Raton, Florida, United States, 33428
      • Investigator Site 45 - US0010108
    • Port Charlotte, Florida, United States, 33952
      • Investigator site 4 - US0010110
    • Tampa, Florida, United States, 41076
      • Investigator Site 39 - US0010006
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Investigator Site 41 - US0010015
  • New York
    • Amherst, New York, United States, 14226
      • Investigator Site 46 - US0010111
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Investigator Site 38 - US0010003
    • Durham, North Carolina, United States, 27710
      • Investigator Site 44 - US0010077
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Investigator Site 42 - US0010019
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Investigator site 7 - US0010008
  • Texas
    • Austin, Texas, United States, 78759
      • Investigator Site 43 - US0010066
    • San Antonio, Texas, United States, 78229
      • Investigator Site 40 - US0010009

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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. Previously participated in antecedent studies ARGX-113-2001 or ARGX-113-1705 and are eligible for roll over.

3. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies and:

   • Women of Child bearing potential (WOCBP) must have a negative urine pregnancy test at baseline before investigational medicinal product (IMP) can be administered.

Exclusion Criteria:

1. The participant was discontinued early from studies ARGX-113-2001 or ARGX-113-1705, unless the reason for discontinuation from study ARGX-113-1705 was to roll over into study ARGX-113-2002.

   a. Participants who, in the investigator's judgment, are not benefiting from efgartigimod IV in study ARGX-113-1705 Part B are not eligible for roll over into ARGX-113-2002.

2. Are pregnant or lactating, or intend to become pregnant during the study or within 90 days after the last dose of investigational medicinal product (IMP)

3. Has any of the following medical conditions:

   1. Clinically significant uncontrolled chronic bacterial, viral, or fungal infection at roll-over
   2. Any other known autoimmune disease that, in the opinion of the investigator, would interfere with 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 investigational medicinal product (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
4. Received a live-attenuated vaccine within 28 days prior to study entry or plan to receive a live-attenuated vaccine during the study
5. A known hypersensitivity reaction to efgartigimod, rHuPH20, or any of its excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: efgartigimod PH20 SC; Patients receiving efgartigimod PH20 subcutaneous (SC) treatment	Biological: efgartigimod PH20 SC; Subcutaneous injection with efgartigimod PH20 SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of Adverse Events (AEs)	Up to 3.5 years
Incidence of Serious Adverse Events (SAEs)	Up to 3.5 years
Incidence of Adverse Events of Special Interest (AESI)	Up to 3.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myasthenia Gravis Activities of Daily Living (MG-ADL) total score changes from baseline	the higher the score, the more impairment	Up to 3.5 years
Cycle baseline over time by cycle (for MG-ADL)		Up to 3.5 years
Percentage change in levels of total immunoglobulin G (IgG) from baseline		Up to 3.5 years
Cycle baseline over time by cycle (for total immunoglobulin G (IgG)		Up to 3.5 years
Percentage change of anti-acetylcholine receptor antibodies (AChR-Ab) from baseline		Up to 3.5 years
Cycle baseline over time by cycle in AChR-Ab seropositive participants (for acetylcholine receptor binding autoantibodies (AChR-Ab))		Up to 3.5 years
Efgartigimod serum concentrations		Up to 3.5 years
Incidence of anti-drug antibodies (ADAs) to efgartigimod over time		Up to 3.5 years
Prevalence of anti-drug antibodies (ADAs) to efgartigimod over time		Up to 3.5 years
Incidence of neutralizing antibodies (NAbs) against efgartigimod over time		Up to 3.5 years
Prevalence of neutralizing antibodies (NAbs) against efgartigimod over time		Up to 3.5 years
Incidence of ADAs to rHuPH20 over time		Up to 3.5 years
Prevalence of ADAs to rHuPH20 over time		Up to 3.5 years
Incidence of NAbs against rHuPH20 over time		Up to 3.5 years
Prevalence of NAbs against rHuPH20 over time		Up to 3.5 years
Changes in total Myasthenia Gravis Quality of Life Questionnaire (15-item scale revised) (MG-QoL15r) from baseline		Up to 3.5 years
Cycle baseline by cycle (for MG-QoL15r)		Up to 3.5 years
Changes in EuroQoL 5 Dimensions 5-Level (EQ-5D-5L) visual analog scale (VAS) score from baseline		Up to 3.5 years
Cycle baseline by cycle (for EQ-5D-5L)		Up to 3.5 years
EQ-5D-5L responses over time by cycle		Up to 3.5 years
Number of participants who performed self-administration at home over time by cycle		Up to 3.5 years
Percentage of participants who performed self-administration at home over time by cycle		Up to 3.5 years
Number of caregivers who administered the injection to the participant at home over time by cycle		Up to 3.5 years
Percentage of caregivers who administered the injection to the participant at home over time by cycle		Up to 3.5 years
Number of training visits needed for the participant or caregiver to be competent to start administering efgartigimod PH20 SC		Up to 3.5 years
Number of self- or caregiver-supported study drug administration among all study treatment visits at home		Up to 3.5 years
Percentage of self- or caregiver-supported study drug administration among all study treatment visits at home		Up to 3.5 years

Collaborators and Investigators

• Sponsor: argenx

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: March 11, 2021
• First Submitted That Met QC Criteria: March 25, 2021
• First Posted (Actual): March 26, 2021

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis
• Other Study ID Numbers: ARGX-113-2002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No