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

Generalized Myasthenia Gravis Clinical Trial

— ADAPTSC+  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04818671
• Other study ID #: ARGX-113-2002
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 26, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• Source: argenx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 183
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Generalized Myasthenia Gravis
• Muscle Weakness
• Myasthenia Gravis

Intervention

Biological:
• efgartigimod PH20 SC
Subcutaneous injection with efgartigimod PH20 SC

Locations

Country	Name	City	State
Belgium	Investigator site 5 - BE0320007	Gent
Czechia	Investigator site 24 - CZ4200005	Brno
Georgia	Investigator Site 1 - GEO9950001	Tbilisi
Georgia	Investigator site 2 - GEO9950002	Tbilisi
Georgia	Investigator site 3 - GEO9950003	Tbilisi
Georgia	Investigator Site 32 - GEO9950004	Tbilisi
Georgia	Investigator Site 33 - GEO9950016	Tbilisi
Germany	Investigator Site 25 - DE490006	Berlin
Germany	Investigator Site 26 - DE490009	Münster
Hungary	Investigator site 10 - HU0360013	Budapest
Hungary	Investigator site 9 - HU0360012	Budapest
Italy	Investigator site 11 - IT0390003	Milano
Italy	Investigator Site 34 - IT0390007	Napoli
Italy	Investigator Site 35 - IT0390008	Roma
Japan	Investigator site 12 - JP0810002	Chiba	Chiba-Shi
Japan	Investigator site 8 - JP0810004	Hanamaki	Iwate
Japan	Investigator site 14 - JP0810007	Osaka
Japan	Investigator Site 28- JP0810059	Ota-Ku	Tokyo
Japan	Investigator Site 27 - JP0810008	Sapporo
Japan	Investigator Site 36 - JP0810055	Sapporo	Hokkaido
Japan	Investigator site 13 - JP0810005	Sendai-shi
Japan	Investigator site 15 - JP0810009	Tokyo
Netherlands	Investigator site 16 - NL0310001	Leiden
Poland	Investigator site 17 - PL0480001	Gdansk
Poland	Investigator site 19 - PL0480007	Katowice
Poland	Investigator site 18 - PL0480005	Kraków
Poland	Investigator site 22 - PL0480065	Kraków
Poland	Investigator site 20 - PL0480018	Lublin
Poland	Investigator site 21 - PL0480022	Warsaw
Russian Federation	Investigator Site 29- RU0070002	Novosibirsk
Russian Federation	Investigator Site 30 - RU0070014	Saint Petersburg
Spain	Investigator Site 31 - ES0340038	Barcelona
Spain	Investigator Site 37 - ES0340021	Barcelona
Spain	Investigator site 23 - ES0340039	Valencia
United States	Investigator Site 46 - US0010111	Amherst	New York
United States	Investigator Site 43 - US0010066	Austin	Texas
United States	Investigator Site 45 - US0010108	Boca Raton	Florida
United States	Investigator site 6 - US0010032	Carlsbad	California
United States	Investigator Site 38 - US0010003	Chapel Hill	North Carolina
United States	Investigator Site 42 - US0010019	Cleveland	Ohio
United States	Investigator site 7 - US0010008	Cordova	Tennessee
United States	Investigator Site 44 - US0010077	Durham	North Carolina
United States	Investigator Site 41 - US0010015	Kansas City	Kansas
United States	Investigator Site 47 - US0010021	Palo Alto	California
United States	Investigator site 4 - US0010110	Port Charlotte	Florida
United States	Investigator Site 40 - US0010009	San Antonio	Texas
United States	Investigator Site 39 - US0010006	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
argenx

Countries where clinical trial is conducted

United States,  Belgium,  Czechia,  Georgia,  Germany,  Hungary,  Italy,  Japan,  Netherlands,  Poland,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of Adverse Events (AEs)		Up to 3.5 years
Primary	Incidence of Serious Adverse Events (SAEs)		Up to 3.5 years
Primary	Incidence of Adverse Events of Special Interest (AESI)		Up to 3.5 years
Secondary	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
Secondary	Cycle baseline over time by cycle (for MG-ADL)		Up to 3.5 years
Secondary	Percentage change in levels of total immunoglobulin G (IgG) from baseline		Up to 3.5 years
Secondary	Cycle baseline over time by cycle (for total immunoglobulin G (IgG)		Up to 3.5 years
Secondary	Percentage change of anti-acetylcholine receptor antibodies (AChR-Ab) from baseline		Up to 3.5 years
Secondary	Cycle baseline over time by cycle in AChR-Ab seropositive participants (for acetylcholine receptor binding autoantibodies (AChR-Ab))		Up to 3.5 years
Secondary	Efgartigimod serum concentrations		Up to 3.5 years
Secondary	Incidence of anti-drug antibodies (ADAs) to efgartigimod over time		Up to 3.5 years
Secondary	Prevalence of anti-drug antibodies (ADAs) to efgartigimod over time		Up to 3.5 years
Secondary	Incidence of neutralizing antibodies (NAbs) against efgartigimod over time		Up to 3.5 years
Secondary	Prevalence of neutralizing antibodies (NAbs) against efgartigimod over time		Up to 3.5 years
Secondary	Incidence of ADAs to rHuPH20 over time		Up to 3.5 years
Secondary	Prevalence of ADAs to rHuPH20 over time		Up to 3.5 years
Secondary	Incidence of NAbs against rHuPH20 over time		Up to 3.5 years
Secondary	Prevalence of NAbs against rHuPH20 over time		Up to 3.5 years
Secondary	Changes in total Myasthenia Gravis Quality of Life Questionnaire (15-item scale revised) (MG-QoL15r) from baseline		Up to 3.5 years
Secondary	Cycle baseline by cycle (for MG-QoL15r)		Up to 3.5 years
Secondary	Changes in EuroQoL 5 Dimensions 5-Level (EQ-5D-5L) visual analog scale (VAS) score from baseline		Up to 3.5 years
Secondary	Cycle baseline by cycle (for EQ-5D-5L)		Up to 3.5 years
Secondary	EQ-5D-5L responses over time by cycle		Up to 3.5 years
Secondary	Number of participants who performed self-administration at home over time by cycle		Up to 3.5 years
Secondary	Percentage of participants who performed self-administration at home over time by cycle		Up to 3.5 years
Secondary	Number of caregivers who administered the injection to the participant at home over time by cycle		Up to 3.5 years
Secondary	Percentage of caregivers who administered the injection to the participant at home over time by cycle		Up to 3.5 years
Secondary	Number of training visits needed for the participant or caregiver to be competent to start administering efgartigimod PH20 SC		Up to 3.5 years
Secondary	Number of self- or caregiver-supported study drug administration among all study treatment visits at home		Up to 3.5 years
Secondary	Percentage of self- or caregiver-supported study drug administration among all study treatment visits at home		Up to 3.5 years