Clinical trial NCT04524273: Myasthenia Gravis Inebilizumab Trial
Official title: A Randomized, Double-blind, Multicenter, Placebo-controlled Phase 3 Study With Open-label Period to Evaluate the Efficacy and Safety of Inebilizumab in Adults With Myasthenia Gravis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Myasthenia Gravis
Keywords: Myasthenia Gravis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2020-08-24
Enrollment: 238
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A Randomized, Double-blind, Multicenter, Placebo-controlled Phase 3 Study with Open-label Period
Primary purpose: TREATMENT

Brief summary: Randomized, double-blind, placebo-controlled, Phase 3, parallel-group study with optional open-label extension.

Detailed description: This study is a phase 3, randomized, double-blind, placebo-controlled study, to be conducted at approximately 120 study sites. Approximately 230 participants (188 acetylcholine receptor antibody positive \[AChR-Ab+\] and 42 muscle-specific tyrosine kinase antibody positive \[MuSK-Ab+\]) will be enrolled. Participants with Myasthenia Gravis (MG) who are positive for anti-AChR or anti-MuSK antibodies will be enrolled and analyzed. Patients who do not have anti-AChR or anti-MuSK antibodies will not be enrolled. Patients with Myasthenia Gravis Foundation of America (MGFA) classification II, III, or IV disease, Myasthenia Gravis Activities of Daily Living (MG-ADL) score at screening and randomization between 6 and 10 with \> 50% of this score attributed to non-ocular items, or an MG-ADL score \>=11, Quantitative Myasthenia Gravis (QMG) score \>= 11 at the time of screening and randomization, and use of a corticosteroid and/or non-steroidal immunosuppressant will be included in the study.

All subjects who complete the randomized controlled period (RCP) will have the option to enroll in a 3-year (156 weeks) open-label period.

Study acquired from Horizon in 2023.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of MG with anti-AChR or anti-MuSK antibody.
2. MGFA Clinical Classification Class II, III, or IV.
3. MG-ADL score of 6 or greater at screening and at randomization with \> 50% of this score attributed to non-ocular items.
4. QMG score of 11 or greater.
5. Participants must be on:

   1. Corticosteroids only, with no dose increase within 4 weeks prior to randomization, or
   2. One allowed non-steroidal immunosuppressive therapy (IST), with continuous use for at least 6 months prior to randomization and no dose increase within 4 months prior to randomization, or
   3. Combination of (1) corticosteroids with no dose increase within 4 weeks prior to randomization and (2) one allowed non-steroidal IST with continuous use for at least 6 months prior to randomization and no dose increase within 4 months prior to randomization.

Allowed ISTs, alone or in combination with corticosteroids, are azathioprine, mycophenolate mofetil, and mycophenolic acid.

Exclusion Criteria:

1. Receipt of the following medications within the 4 weeks prior to Day 1:

   1. Cyclosporine (except eye drops)
   2. Tacrolimus (except topical)
   3. Methotrexate
2. Current use of:

   1. Corticosteroids (Prednisone \> 40 milligram (mg)/day or \> 80 mg over a 2-day period (or equivalent dose of other corticosteroids).
   2. Acetylcholinesterase inhibitors (pyridostigmine) \> 480 mg/day) or unstable dose in the 2 weeks prior to Day 1.
   3. Azathioprine \> 3 mg/kilogram (kg)/day
   4. Mycophenolate mofetil \> 3 grams/day or mycophenolic acid \> 1440 mg/day
   5. Any IST, alone or in combination with corticosteroids, except for azathioprine, mycophenolate mofetil, and mycophenolic acid.

Primary outcomes:
measure: Change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) Profile score.
timeFrame: Baseline to Week 26
Secondary outcomes:
measure: Change from baseline in Quantitative Myasthenia Gravis (QMG) scores.
timeFrame: Baseline to Week 52 for AChR-Ab+ population and Week 26 for the overall study population
measure: Proportion of participants with both ≥ 3-point improvement from baseline in MG-ADL and did not initiate rescue therapy.
timeFrame: Baseline to Week 52 for AChR-Ab+ population and Week 26 for the overall study population
measure: Change from baseline in MG-ADL
timeFrame: Baseline to Week 52 for AChR-Ab+ population and Week 26 for the overall study population
measure: Time to first gMG exacerbation.
timeFrame: Day 1 to Week 52 for AChR-Ab+ population and Week 26 for the overall study population
measure: Change from baseline in Myasthenia Gravis Composite (MGC) score.
timeFrame: Baseline to Week 52 for AChR-Ab+ population and Week 26 for the overall study population
measure: Change from baseline in Myasthenia Gravis Quality of Life-15, revised (MGQOL-15r) score.
timeFrame: Baseline to Week 52 for AChR-Ab+ population and Week 26 for the overall study population
measure: Patient Global Impression of Change (PGIC) score.
timeFrame: Week 52 for AChR-Ab+ population and Week 26 for the overall study population
measure: Number of participants with treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), and treatment-emergent serious adverse events (TESAEs) during the RCP and OLP.
timeFrame: Up to 208 weeks
measure: Proportion of participants with steroid tapered to ≤ 5 mg/day.
timeFrame: Week 52 for AChR-Ab+ population and Week 26 for the overall study population
measure: Proportion of participants with a steroid dose reduction from baseline of ≥ 50%.
timeFrame: Baseline to Week 52 for AChR-Ab+ population and Week 26 for the overall study population
measure: Proportion of participants achieving minimal symptom expression.
timeFrame: Week 26
measure: Proportion of participants with anti-drug antibodies (ADAs) to inebilizumab
timeFrame: Up to 208 weeks
measure: Titers of ADAs
timeFrame: Up to 208 weeks
Other outcomes:
Locations:
city: Orange
country: United States
facility: Viela Bio Investigative Site - 1015
state: California
city: New Haven
country: United States
facility: Viela Bio Investigative Site - 1002
state: Connecticut
city: Washington
country: United States
facility: Viela Bio Investigative Center - 1024
state: District of Columbia
city: Tampa
country: United States
facility: Viela Bio Investigative Site - 1005
state: Florida
city: Kansas City
country: United States
facility: Viela Bio Investigative Site - 1012
state: Kansas
city: Charlotte
country: United States
facility: Viela Bio Investigative Site - 1018
state: North Carolina
city: Canton
country: United States
facility: Viela Bio Investigative Site - 1025
state: Ohio
city: Cincinnati
country: United States
facility: Viela Bio Investigative Site - 1001
state: Ohio
city: Columbus
country: United States
facility: Viela Bio Investigative Site - 1009
state: Ohio
city: Pittsburgh
country: United States
facility: Viela Bio Investigative Site - 1008
state: Pennsylvania
city: Austin
country: United States
facility: Viela Bio Investigative Site - 1019
state: Texas
city: Houston
country: United States
facility: Viela Bio Investigative Site - 1003
state: Texas
city: San Antonio
country: United States
facility: Viela Bio Investigative Site - 1014
state: Texas
city: Salt Lake City
country: United States
facility: Viela Bio Investigative Site - 1017
state: Utah
city: Burlington
country: United States
facility: Viela Bio Investigative Site - 1004
state: Vermont
city: Richmond
country: United States
facility: Viela Bio Investigative Site - 1006
state: Virginia
city: Buenos Aires
country: Argentina
facility: Viela Bio Investigative Site - 2001
city: Buenos Aires
country: Argentina
facility: VielaBio Investigative Site - 2002
city: Buenos Aires
country: Argentina
facility: Viela Bio Investigative Site - 2003
city: Grodno
country: Belarus
facility: Viela Bio Investigative Site - 5203
city: Minsk
country: Belarus
facility: Viela Bio Investigative Site - 5204
city: Vitebsk
country: Belarus
facility: Viela Bio Investigative Site - 5201
city: Porto Alegre
country: Brazil
facility: VielaBio Investigative Site - 2201
city: Porto Alegre
country: Brazil
facility: VielaBio Investigative Site - 2203
city: Ribeirão Preto
country: Brazil
facility: VielaBio Investigative Site - 2207
city: San Paolo
country: Brazil
facility: VielaBio Investigative Site - 2206
city: São Paulo
country: Brazil
facility: Viela Bio Investigative Site - 2205
city: Toronto
country: Canada
facility: Viela Bio Investigative Site - 1102
state: Ontario
city: Montréal
country: Canada
facility: Viela Bio Investigative Site - 1101
state: Quebec
city: Montréal
country: Canada
facility: Viela Bio Investigative Site - 1103
state: Quebec
city: Beijing
country: China
facility: Viela Bio Investigative Site 4009
city: Beijing
country: China
facility: Viela Bio Investigative Site - 4007
city: Beijing
country: China
facility: Viela Bio Investigative Site 4003
city: Guiyang
country: China
facility: Viela Bio Investigative Site - 4005
city: Hunan
country: China
facility: Viela Bio Investigative site 4010
city: Jinan
country: China
facility: Viela Bio Investigative Site - 4011
city: Shanghai
country: China
facility: Viela Bio Investigative Site - 4006
city: Suzhou
country: China
facility: Viela Bio Investigative Site - 4008
city: Tianjin
country: China
facility: Viela Bio Investigative Site - 4004
city: Xi'an
country: China
facility: Viela Bio Investigative Site 4012
city: Copenhagen
country: Denmark
facility: Viela Bio Investigative Site - 5601
city: Lille Cedex
country: France
facility: Viela Bio Investigative Site - 3003
city: Nice Cedex 01
country: France
facility: Viela Bio Investigative Site - 3001
city: Strasbourg
country: France
facility: Viela Bio Investigative Site - 3002
city: Essen
country: Germany
facility: VielaBio Investigative Site - 3101
city: Nagpur
country: India
facility: Viela Bio Investigative Site - 4107
state: Maharashtra
city: Nagpur
country: India
facility: Viela Bio Investigative Site - 4113
state: Maharashtra
city: Hyderabad
country: India
facility: Viela Bio Investigative Site - 4112
state: Telangana
city: Bangalore
country: India
facility: Viela Bio Investigative Site - 4104
city: Lucknow
country: India
facility: Viela Bio investigative Site - 4105
city: Manipala
country: India
facility: Viela Bio Investigative Site - 4103
city: Nashik
country: India
facility: Viela Bio Investigative Site - 4102
city: Pune
country: India
facility: Viela Bio Investigative Site - 4109
city: Surat
country: India
facility: Viela Bio Investigative Site - 4101
city: Milano
country: Italy
facility: Viela Bio Investigative Site - 3204
city: Milano
country: Italy
facility: Viela Bio Investigative Site - 3203
city: Pavia
country: Italy
facility: Viela Bio Investigative Site - 3201
city: Rome
country: Italy
facility: Viela Bio Investigative Site - 3202
city: Chiba
country: Japan
facility: Viela Bio Investigative Site - 4402
city: Chiba
country: Japan
facility: Viela Bio Investigative Site - 4410
city: Fukuoka
country: Japan
facility: Viela Bio Investigative Site 4409
city: Hanamaki
country: Japan
facility: Viela Bio Investigative Site - 4401
city: Hokkaido
country: Japan
facility: VielaBio Investigative Site - 4408
city: Hyōgo
country: Japan
facility: Viela Bio Investigative Site - 4406
city: Miyagi
country: Japan
facility: Viela Bio Investigative Site 4405
city: Moriguchi
country: Japan
facility: Viela Bio Investigative Site - 4413
city: Morioka-shi
country: Japan
facility: VielaBio Investigative Site - 4407
city: Saitama
country: Japan
facility: Viela Bio Investigative Site - 4404
city: Seoul
country: Korea, Republic of
facility: Viela Bio Investigative Site - 4202
city: Seoul
country: Korea, Republic of
facility: Viela Bio Investigative Site - 4203
city: Seoul
country: Korea, Republic of
facility: Viela Bio Investigative Site - 4201
city: Katowice
country: Poland
facility: Viela Bio Investigative Site - 3302
city: Katowice
country: Poland
facility: Viela Bio Investigative Site - 3303
city: Kraków
country: Poland
facility: Viela Bio Investigative Site - 3301
city: Poznań
country: Poland
facility: Med Polonia Sp. z o.o - 3311
city: Warszawa
country: Poland
facility: Viela Bio Investigative Site - 3310
city: Barnaul
country: Russian Federation
facility: Viela Bio Investigative Site - 5313
state: Altai Krai
city: Barnaul
country: Russian Federation
facility: Viela Bio Investigative Site - 5303
city: Nizhny Novgorod
country: Russian Federation
facility: Viela Bio Investigative Site - 5302
city: Novosibirsk
country: Russian Federation
facility: Viela Bio Investigative Site - 5304
city: Rostov-on-Don
country: Russian Federation
facility: Viela Bio Investigative Site - 5311
city: Rostov-on-Don
country: Russian Federation
facility: Viela Bio Investigative Site - 5309
city: Saint Petersburg
country: Russian Federation
facility: Viela Bio Investigative Site - 5308
city: Samara
country: Russian Federation
facility: Viela Bio Investigative Site - 5305
city: Ufa
country: Russian Federation
facility: Viela Bio Investigative Site - 5312
city: Badalona
country: Spain
facility: Viela Bio Investigative Site - 3403
city: Barcelona
country: Spain
facility: Viela Bio Investigative Site - 3402
city: Córdoba
country: Spain
facility: Viela Bio Investigative Site - 3404
city: Kaohsiung City
country: Taiwan
facility: Viela Bio investigative Site - 4605
city: New Taipei City
country: Taiwan
facility: Viela Bio Investigative Site 4608
city: Tainan
country: Taiwan
facility: Viela Bio Investigative Site - 4606
city: Taipei
country: Taiwan
facility: Viela Bio Investigative Site - 4604
city: Taipei
country: Taiwan
facility: Viela Bio Investigative Site - 4603
city: Taipei
country: Taiwan
facility: Viela Bio Investigative Site -4607
city: Taoyuan City
country: Taiwan
facility: Viela Bio Investigative Site - 4602
city: Ankara
country: Turkey
facility: Viela Bio Investigative Site - 3903
city: İzmir
country: Turkey
facility: Viela Bio Investigative Site - 3901
city: İzmir
country: Turkey
facility: Viela Bio Investigative Site - 3902
city: Kocaeli
country: Turkey
facility: Viela Bio Investigative Site - 3905
city: Dnipro
country: Ukraine
facility: Viela Bio Investigative Site - 5103
city: Dnipro
country: Ukraine
facility: Viela Bio Investigative Site - 5108
city: Ivano-Frankivs'k
country: Ukraine
facility: Viela Bio Investigative Site - 5105
city: Lutsk
country: Ukraine
facility: Viela Bio Investigative Site - 5104
city: Vinnytsia
country: Ukraine
facility: Viela Bio Investigative Site - 5106
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: