An Efficacy and Safety Study of ARGX-113 in Patients With Myasthenia Gravis Who Have Generalized Muscle Weakness

Generalized Myasthenia Gravis Clinical Trial

— ADAPT  

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase 3 Trial to Evaluate the Efficacy, Safety and Tolerability of ARGX-113 in Patients With Myasthenia Gravis Having Generalized Muscle Weakness

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03669588
• Other study ID #: ARGX-113-1704
• Secondary ID: 2018-002132-25
• Status: Completed
• Phase: Phase 3
• Start date: August 22, 2018
• Est. completion date: April 6, 2020

Study information

• Verified date: March 2021
• Source: argenx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A randomized, double-blind, placebo controlled, multicenter Phase 3 trial to evaluate the efficacy, safety, tolerability, quality of life and impact on normal daily activities of ARGX-113 in patients with gMG.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 167
• Est. completion date: April 6, 2020
• Est. primary completion date: April 6, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients with the ability to understand the requirements of the trial, provide written informed consent, and comply with the trial protocol procedures.

2. Male or female patients aged = 18 years.

3. Diagnosis of MG with generalized muscle weakness meeting the clinical criteria for diagnosis of MG as defined by the Myasthenia Gravis Foundation of America (MGFA) class II, III, IVa and IVb. Other, more specific inclusion criteria are defined in the protocol

Exclusion Criteria:

1. Pregnant and lactating women, and those intending to become pregnant during the trial or within 90 days after the last dosing.

2. Male patients who are sexually active and do not intend to use effective methods of contraception during the trial or within 90 days after the last dosing or male patients who plan to donate sperm during the trial or within 90 days after the last dosing.

3. MGFA Class I and V patients.

4. Patients with worsening muscle weakness secondary to concurrent infections or medications.

5. Patients with known seropositivity or who test positive for an active viral infection

at Screening with:

• Hepatitis B Virus (HBV) (except patients who are seropositive because of HBV vaccination)
• Hepatitis C Virus (HCV)
• Human Immunodeficiency Virus (HIV) Other, more specific exclusion criteria are further defined in the protocol.

Related Conditions & MeSH terms

• Generalized Myasthenia Gravis
• Muscle Weakness
• Myasthenia Gravis
• Paresis

Intervention

Biological:
• ARGX-113
Intravenous administration of ARGX-113
• Placebo
Intravenous administration of placebo

Locations

Country	Name	City	State
Belgium	Investigator Site 11	Edegem
Belgium	Investigator Site 8	Ghent
Canada	Investigator Site 38	Edmonton	Alberta
Canada	Investigator Site 22	Montréal	Quebec
Canada	Investigator Site 24	Toronto	Ontario
Czechia	Investigator Site 32	Brno
Czechia	Investigator Site 35	Ostrava-Poruba
Czechia	Investigator Site 51	Praha 2
Denmark	Investigator Site 36	Aarhus
Denmark	Investigator Site 15	Copenhagen
France	Investigator Site 13	Bordeaux Cedex
France	Investigator Site 52	Marseille
Georgia	Investigator Site 45	Tbilisi
Georgia	Investigator Site 46	Tbilisi
Georgia	Investigator Site 47	Tbilisi
Germany	Investigator Site 33	Berlin
Hungary	Investigator Site 55	Budapest
Hungary	Investigator Site 54	Szeged
Italy	Investigator Site 10	Milano
Italy	Investigator Site 12	Napoli
Japan	Investigator Site 42	Chiba-shi	Chiba
Japan	Investigator Site 19	Hanamaki	Iwate
Japan	Investigator Site 31	Meguro	Tokyo
Japan	Investigator Site 41	Minato-Ku	Tokyo
Japan	Investigator Site 28	Osaka-sayama	Osaka
Japan	Investigator Site 26	Sapporo	Hokkaido
Japan	Investigator Site 43	Sendai	Miyagi
Japan	Investigator Site 39	Shinjuku-Ku	Tokyo
Japan	Investigator Site 50	Suita	Osaka
Netherlands	Investigator Site 37	Leiden
Poland	Investigator Site 7	Gdansk
Poland	Investigator Site 57	Katowice
Poland	Investigator Site 14	Kraków
Poland	Investigator Site 23	Warszawa
Russian Federation	Investigator Site 64	Krasnoyarsk
Russian Federation	Investigator Site 62	Nizhny Novgorod
Russian Federation	Investigator Site 65	Novosibirsk
Russian Federation	Investigator Site 60	Samara
Serbia	Investigator Site 61	Belgrade
United Kingdom	Investigator Site 63	Edgbaston
United Kingdom	Investigator Site 56	Liverpool
United States	Investigator Site 58	Aurora	Colorado
United States	Investigator Site 27	Boston	Massachusetts
United States	Investigator Site 53	Buffalo	New York
United States	Investigator Site 66	Carlsbad	California
United States	Investigator Site 3	Chapel Hill	North Carolina
United States	Investigator Site 17	Charleston	South Carolina
United States	Investigator Site 2	Charlottesville	Virginia
United States	Investigator Site 20	Cleveland	Ohio
United States	Investigator Site	Cordova	Tennessee
United States	Investigator Site 48	Detroit	Michigan
United States	Investigator Site 44	Houston	Texas
United States	Investigator Site 25	Iowa City	Iowa
United States	Investigator Site 34	Jacksonville	Florida
United States	Investigator Site 21	Kansas City	Kansas
United States	Investigator Site 49	Los Angeles	California
United States	Investigator Site 5	Los Angeles	California
United States	Investigator Site 18	Orange	California
United States	Investigator Site 40	Palo Alto	California
United States	Investigator Site 29	Phoenix	Arizona
United States	Investigator Site 9	Portland	Oregon
United States	Investigator Site 6	San Antonio	Texas
United States	Investigator Site 59	San Francisco	California
United States	Investigator Site 16	Seattle	Washington
United States	Investigator Site 30	Springfield	Illinois
United States	Investigator Site 4	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
argenx

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  Denmark,  France,  Georgia,  Germany,  Hungary,  Italy,  Japan,  Netherlands,  Poland,  Russian Federation,  Serbia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of MG-ADL Responders During Cycle 1 (C1); Analyzed in the AChR-Ab Seropositive Population	The MG-ADL is an 8-item patient-reported scale to assess MG symptoms and their effects on daily activities. The scale comprises 2 items on daily life activities and 6 items on symptoms. The MG-ADL total score range is 0-24, with higher scores indicative of greater disease severity. A patient was considered an MG-ADL responder during C1 if there was a reduction of =2 points on the MG-ADL total score (compared to baseline of C1 [C1B]) for =4 consecutive weeks with the first reduction occurring no later than 1 week after the last infusion of IMP in C1.	Baseline up to Day 63 (end of TC1)
Secondary	Percentage of Quantitative Myasthenia Gravis (QMG) Responders During C1; Analyzed in the AChR-Ab Seropositive Population	The QMG scale quantifies disease severity based on impairments of body functions and structures as defined by the International Classification of Disability and Health. The QMG scale consists of 13 items that measure endurance or fatigability, and accounts for fluctuations in disease state. The QMG total score range is 0-39, with higher scores indicative of greater disease severity. A patient was considered a QMG responder during C1 if there was a reduction of =3-points on the QMG total score (compared to C1B) for =4 consecutive weeks with the first reduction occurring no later than 1 week after the last infusion of IMP in C1.	Baseline up to Day 63 (end of TC1)
Secondary	Percentage of MG-ADL Responders During C1; Analyzed in the Overall Population	The percentage of MG-ADL responders during C1 in the overall population is reported for this secondary end point; percentage of MG-ADL responders during C1 in the AChR-Ab seropositive population is reported previously as a primary end point.	Baseline up to Day 63 (end of TC1)
Secondary	Percentage of Time That Patients Had a Clinically Meaningful Improvement (CMI) in MG-ADL Total Score up to and Including Day 126; Analyzed in the AChR-Ab Seropositive Population	An MG-ADL CMI was defined as a reduction of =2 points on the total MG-ADL score compared to study entry baseline (SEB).	Baseline up to Day 126
Secondary	Time From Week 4 to Qualify for Retreatment; Analyzed in the AChR-Ab Seropositive Population	Time to qualify for retreatment was defined as time from the Week 4 assessment until the first visit with a <2-point reduction compared to SEB in the MG-ADL total score and MG-ADL total score =5 points with >50% of the total score attributable to nonocular symptoms.	Week 4 up to Day 182 (end of study [EoS])
Secondary	Percentage of Early MG-ADL Responders During C1; Analyzed in the AChR-Ab Seropositive Population	A patient was considered an early MG-ADL responder during C1 if there was a reduction of =2 points on the MG-ADL total score (compared to C1B) for =4 consecutive weeks with the first reduction occurring no later than Week 2 (ie, after 1 or maximum 2 infusions of IMP in C1).	Baseline up to Day 63 (end of TC1)