Clinical trial NCT04818671: Evaluating the Long-Term Safety and Tolerability of Efgartigimod PH20 SC Administered Subcutaneously in Patients with Generalized Myasthenia Gravis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Generalized Myasthenia Gravis
Lead sponsor: argenx
Sponsor class: INDUSTRY
First posted: 2021-03-26
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Incidence and severity of Adverse Events (AEs)
timeFrame: Up to 3.5 years
measure: Incidence of Serious Adverse Events (SAEs)
timeFrame: Up to 3.5 years
measure: Incidence of Adverse Events of Special Interest (AESI)
timeFrame: Up to 3.5 years
Secondary outcomes:
measure: Myasthenia Gravis Activities of Daily Living (MG-ADL) total score changes from baseline
timeFrame: Up to 3.5 years
measure: Cycle baseline over time by cycle (for MG-ADL)
timeFrame: Up to 3.5 years
measure: Percentage change in levels of total immunoglobulin G (IgG) from baseline
timeFrame: Up to 3.5 years
measure: Cycle baseline over time by cycle (for total immunoglobulin G (IgG)
timeFrame: Up to 3.5 years
measure: Percentage change of anti-acetylcholine receptor antibodies (AChR-Ab) from baseline
timeFrame: Up to 3.5 years
measure: Cycle baseline over time by cycle in AChR-Ab seropositive participants (for acetylcholine receptor binding autoantibodies (AChR-Ab))
timeFrame: Up to 3.5 years
measure: Efgartigimod serum concentrations
timeFrame: Up to 3.5 years
measure: Incidence of anti-drug antibodies (ADAs) to efgartigimod over time
timeFrame: Up to 3.5 years
measure: Prevalence of anti-drug antibodies (ADAs) to efgartigimod over time
timeFrame: Up to 3.5 years
measure: Incidence of neutralizing antibodies (NAbs) against efgartigimod over time
timeFrame: Up to 3.5 years
measure: Prevalence of neutralizing antibodies (NAbs) against efgartigimod over time
timeFrame: Up to 3.5 years
measure: Incidence of ADAs to rHuPH20 over time
timeFrame: Up to 3.5 years
measure: Prevalence of ADAs to rHuPH20 over time
timeFrame: Up to 3.5 years
measure: Incidence of NAbs against rHuPH20 over time
timeFrame: Up to 3.5 years
measure: Prevalence of NAbs against rHuPH20 over time
timeFrame: Up to 3.5 years
measure: Changes in total Myasthenia Gravis Quality of Life Questionnaire (15-item scale revised) (MG-QoL15r) from baseline
timeFrame: Up to 3.5 years
measure: Cycle baseline by cycle (for MG-QoL15r)
timeFrame: Up to 3.5 years
measure: Changes in EuroQoL 5 Dimensions 5-Level (EQ-5D-5L) visual analog scale (VAS) score from baseline
timeFrame: Up to 3.5 years
measure: Cycle baseline by cycle (for EQ-5D-5L)
timeFrame: Up to 3.5 years
measure: EQ-5D-5L responses over time by cycle
timeFrame: Up to 3.5 years
measure: Number of participants who performed self-administration at home over time by cycle
timeFrame: Up to 3.5 years
measure: Percentage of participants who performed self-administration at home over time by cycle
timeFrame: Up to 3.5 years
measure: Number of caregivers who administered the injection to the participant at home over time by cycle
timeFrame: Up to 3.5 years
measure: Percentage of caregivers who administered the injection to the participant at home over time by cycle
timeFrame: Up to 3.5 years
measure: Number of training visits needed for the participant or caregiver to be competent to start administering efgartigimod PH20 SC
timeFrame: Up to 3.5 years
measure: Number of self- or caregiver-supported study drug administration among all study treatment visits at home
timeFrame: Up to 3.5 years
measure: Percentage of self- or caregiver-supported study drug administration among all study treatment visits at home
timeFrame: Up to 3.5 years
Other outcomes:
Locations:
city: Carlsbad
country: United States
facility: Investigator site 6 - US0010032
state: California
city: Palo Alto
country: United States
facility: Investigator Site 47 - US0010021
state: California
city: Boca Raton
country: United States
facility: Investigator Site 45 - US0010108
state: Florida
city: Port Charlotte
country: United States
facility: Investigator site 4 - US0010110
state: Florida
city: Tampa
country: United States
facility: Investigator Site 39 - US0010006
state: Florida
city: Kansas City
country: United States
facility: Investigator Site 41 - US0010015
state: Kansas
city: Amherst
country: United States
facility: Investigator Site 46 - US0010111
state: New York
city: Chapel Hill
country: United States
facility: Investigator Site 38 - US0010003
state: North Carolina
city: Durham
country: United States
facility: Investigator Site 44 - US0010077
state: North Carolina
city: Cleveland
country: United States
facility: Investigator Site 42 - US0010019
state: Ohio
city: Cordova
country: United States
facility: Investigator site 7 - US0010008
state: Tennessee
city: Austin
country: United States
facility: Investigator Site 43 - US0010066
state: Texas
city: San Antonio
country: United States
facility: Investigator Site 40 - US0010009
state: Texas
city: Gent
country: Belgium
facility: Investigator site 5 - BE0320007
city: Brno
country: Czechia
facility: Investigator site 24 - CZ4200005
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: Tbilisi
country: Georgia
facility: Investigator Site 32 - GEO9950004
city: Tbilisi
country: Georgia
facility: Investigator Site 33 - GEO9950016
city: Berlin
country: Germany
facility: Investigator Site 25 - DE490006
city: Münster
country: Germany
facility: Investigator Site 26 - DE490009
city: Budapest
country: Hungary
facility: Investigator site 10 - HU0360013
city: Budapest
country: Hungary
facility: Investigator site 9 - HU0360012
city: Milano
country: Italy
facility: Investigator site 11 - IT0390003
city: Napoli
country: Italy
facility: Investigator Site 34 - IT0390007
city: Roma
country: Italy
facility: Investigator Site 35 - IT0390008
city: Chiba
country: Japan
facility: Investigator site 12 - JP0810002
state: Chiba-Shi
city: Sapporo
country: Japan
facility: Investigator Site 36 - JP0810055
state: Hokkaido
city: Hanamaki
country: Japan
facility: Investigator site 8 - JP0810004
state: Iwate
city: Ota-Ku
country: Japan
facility: Investigator Site 28- JP0810059
state: Tokyo
city: Osaka
country: Japan
facility: Investigator site 14 - JP0810007
city: Sapporo
country: Japan
facility: Investigator Site 27 - JP0810008
city: Sendai-shi
country: Japan
facility: Investigator site 13 - JP0810005
city: Tokyo
country: Japan
facility: Investigator site 15 - JP0810009
city: Leiden
country: Netherlands
facility: Investigator site 16 - NL0310001
city: Gdańsk
country: Poland
facility: Investigator site 17 - PL0480001
city: Katowice
country: Poland
facility: Investigator site 19 - PL0480007
city: Kraków
country: Poland
facility: Investigator site 22 - PL0480065
city: Kraków
country: Poland
facility: Investigator site 18 - PL0480005
city: Lublin
country: Poland
facility: Investigator site 20 - PL0480018
city: Warsaw
country: Poland
facility: Investigator site 21 - PL0480022
city: Novosibirsk
country: Russian Federation
facility: Investigator Site 29- RU0070002
city: Saint Petersburg
country: Russian Federation
facility: Investigator Site 30 - RU0070014
city: Barcelona
country: Spain
facility: Investigator Site 37 - ES0340021
city: Barcelona
country: Spain
facility: Investigator Site 31 - ES0340038
city: Valencia
country: Spain
facility: Investigator site 23 - ES0340039
Study officials:
References: