Clinical trial NCT01997229: Safety and Efficacy of Eculizumab in Refractory Generalized Myasthenia Gravis (REGAIN Study)
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Eculizumab in Subjects With Refractory Generalized Myasthenia Gravis (gMG)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Refractory Generalized Myasthenia Gravis
Keywords: Myasthenia Gravis
Eculizumab
safety
efficacy
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2013-11-28
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if eculizumab is safe and effective for the treatment of refractory generalized Myasthenia Gravis.


Eligibility criteria: Key Inclusion Criteria:

* Male or female patients ≥18 years old
* Diagnosis of MG made by the following tests:

  1. Positive serologic test for anti-AChR Abs as confirmed at screening, and
  2. One of the following:

     1. History of abnormal neuromuscular transmission test demonstrated by single-fiber electromyography (SFEMG) or repetitive nerve stimulation, or
     2. History of positive anticholinesterase test, e.g. edrophonium chloride test, or
     3. Subject has demonstrated improvement in MG signs on oral cholinesterase inhibitors, as assessed by the treating physician.
* MGFA Clinical Classification Class II to IV at screening.
* MG-ADL total score must be ≥6 at screening and Randomization (Day 1).
* Subjects who have:

  1. Failed treatment with at least two immunosuppressive agents. Or,
  2. Failed treatment with at least one immunosuppressive agent and require chronic plasma exchange or IVIg

Key Exclusion Criteria:

* History of thymoma or other neoplasms of the thymus
* History of thymectomy within 12 months prior to screening
* MGFA Class I or MG crisis at screening (MGFA Class V)
* Use of rituximab within 6 months prior to screening
* Use of IVIg or PE within 4 weeks prior to Randomization (Day 1)

Primary outcomes:
measure: Myasthenia Gravis Activities of Daily Living Profile (MG-ADL): Change From Baseline in MG-ADL Total Score at Week 26 by Worst-Rank Analysis of Covariance (ANCOVA)
timeFrame: End of study (Week 26)
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Fresno
country: United States
facility: University of California San Francisco-Fresno
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Orange
country: United States
facility: University of California-Irvine
state: California
city: Sacramento
country: United States
facility: University of California Davis Health System
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Jacksonville
country: United States
facility: University of Florida Health Science Center
state: Florida
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Augusta
country: United States
facility: Georgia Regents University
state: Georgia
city: Canton
country: United States
facility: Medical Associates of North Georgia
state: Georgia
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa College of Medicine
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University School Of Medicine
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic Inc.
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University School of Medicine
state: Michigan
city: Las Vegas
country: United States
facility: Las Vegas Clinic
state: Nevada
city: Buffalo
country: United States
facility: Buffalo General Hospital
state: New York
city: New York
country: United States
facility: Hospital For Special Surgery/New York Presbyterian Hospital Cornell Campus
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Healthcare System
state: North Carolina
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Cordova
country: United States
facility: Wesley Neurology Clinic
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Medical Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
city: Houston
country: United States
facility: Methodist Neurological Institute
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Ciudad Autonoma
country: Argentina
facility: Hospital Italiano
state: Buenos Aires
city: Ciudad Autonoma
country: Argentina
facility: Instituto de Investigaciones Neurologicas Raul Carrea, FLENI
state: Buenos Aires
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: AZ Sint-Lucas - Campus Sint-Lucas
city: Leuven
country: Belgium
facility: UZ Leuven
city: Porto Alegre
country: Brazil
facility: Hospital Mãe de Deus
state: Rio Grande Do Sul
city: Santo André
country: Brazil
facility: Faculdade de Medicina do ABC
state: Sao Paulo
city: São José do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto
state: Sao Paulo
city: Rio De Janeiro
country: Brazil
facility: HUCFF-UFRJ - Hospital Universitário Clementino Fraga Filho - Universidade Federal do Rio de Janeiro
city: São Paulo
country: Brazil
facility: UNIFESP - Universidade Federal de São Paulo
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Neurological Institute
state: Quebec
city: Praha
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
state: Prague
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Ostrava - Poruba
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Aarhus C
country: Denmark
facility: Århus Universitetshospital
city: København Ø
country: Denmark
facility: Rigshospitalet
city: Helsinki
country: Finland
facility: Helsingin yliopistollinen keskussairaala
city: Turku
country: Finland
facility: Neuro NEO Oy
city: Nice Cedex 3
country: France
facility: CHU de Nice Hôpital Pasteur 2
state: Alpes Maritimes
city: Bordeaux Cedex
country: France
facility: Groupe Hospitalier Pellegrin - Hôpital Pellegrin
state: Gironde
city: Lille Cedex
country: France
facility: Hopital Roger Salengro - CHU Lille
state: Nord
city: Bron cedex
country: France
facility: Hopital Neurologique Pierre Wertheimer
state: Rhone
city: Muenchen
country: Germany
facility: LMU-Campus Innenstadt
state: Bayern
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Athens
country: Greece
facility: Navy Hospital of Athens
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki "G. Papanikolaou"
city: Budapest
country: Hungary
facility: Jahn Ferenc Del-Pesti Korhaz
city: Szeged
country: Hungary
facility: Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin. Közp.
city: Catania
country: Italy
facility: Policlinico di Catania
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria "Federico II"
city: Padova
country: Italy
facility: Ospedale San Camillo IRCCS
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Roma
country: Italy
facility: Umberto I Pol. di Roma-Università di Roma La Sapienza
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea - Università di Roma La Sapienza
city: Trento
country: Italy
facility: Ospedale Santa Chiara
city: Chiba-shi
country: Japan
facility: Chiba University Hospital
state: Chiba-Ken
city: Fukuoka-shi
country: Japan
facility: Kyushu University Hospital
state: Fukuoka-Ken
city: Sapporo-shi
country: Japan
facility: Sapporo Medical University Hospital
state: Hokkaido
city: Hanamaki-shi
country: Japan
facility: Hanamaki General Hospitals
state: Iwate-Ken
city: Sendai-shi
country: Japan
facility: NHO Sendai Medical Center
state: Miyagi-Ken
city: Kawatana
country: Japan
facility: NHO Nagasaki Kawatana Medical Center
state: Nagasaki-Ken
city: Nagasaki-shi
country: Japan
facility: Nagasaki University Hospital
state: Nagasaki-Ken
city: Osakasayama-shi
country: Japan
facility: Kinki University Hospital
state: Osaka-Fu
city: Suita-shi
country: Japan
facility: Osaka University Hospital
state: Osaka-Fu
city: Meguro-ku
country: Japan
facility: Toho University Ohashi Medical Center
state: Tokyo-To
city: Ube-shi
country: Japan
facility: Yamaguchi University Hospital
state: Yamaguchi-Ken
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul Metropolitan Government Seoul National University
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Leiden
country: Netherlands
facility: Leiden Universitair Medisch Centrum
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Göteborg
country: Sweden
facility: Sahlgrenska Sjukhuset
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset - Solna
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Istanbul
country: Turkey
facility: Karadeniz Tecnical Uni. Med. Fac.
city: Izmir
country: Turkey
facility: Dokuz Eylul University Medicine Faculty
city: Kocaeli
country: Turkey
facility: Kocaeli University Medical Faculty
city: Samsun
country: Turkey
facility: Ondokuz Mayıs University of Medicine
city: Liverpool
country: United Kingdom
facility: The Walton Centre
state: Merseyside
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
state: West Midlands
city: London
country: United Kingdom
facility: King's College Hospital
Study officials:
References:
citation: Howard JF Jr, Barohn RJ, Cutter GR, Freimer M, Juel VC, Mozaffar T, Mellion ML, Benatar MG, Farrugia ME, Wang JJ, Malhotra SS, Kissel JT; MG Study Group. A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis. Muscle Nerve. 2013 Jul;48(1):76-84. doi: 10.1002/mus.23839. Epub 2013 Apr 30.
citation: Howard JF Jr, Utsugisawa K, Benatar M, Murai H, Barohn RJ, Illa I, Jacob S, Vissing J, Burns TM, Kissel JT, Muppidi S, Nowak RJ, O'Brien F, Wang JJ, Mantegazza R; REGAIN Study Group. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study. Lancet Neurol. 2017 Dec;16(12):976-986. doi: 10.1016/S1474-4422(17)30369-1. Epub 2017 Oct 20.
citation: Monteleone JPR, Gao X, Kleijn HJ, Bellanti F, Pelto R. Eculizumab Pharmacokinetics and Pharmacodynamics in Patients With Generalized Myasthenia Gravis. Front Neurol. 2021 Nov 2;12:696385. doi: 10.3389/fneur.2021.696385. eCollection 2021.
citation: Siddiqi ZA, Nowak RJ, Mozaffar T, O'Brien F, Yountz M, Patti F; REGAIN Study Group. Eculizumab in refractory generalized myasthenia gravis previously treated with rituximab: subgroup analysis of REGAIN and its extension study. Muscle Nerve. 2021 Dec;64(6):662-669. doi: 10.1002/mus.27422. Epub 2021 Oct 14.
citation: Nowak RJ, Muppidi S, Beydoun SR, O'Brien FL, Yountz M, Howard JF Jr. Concomitant Immunosuppressive Therapy Use in Eculizumab-Treated Adults With Generalized Myasthenia Gravis During the REGAIN Open-Label Extension Study. Front Neurol. 2020 Nov 24;11:556104. doi: 10.3389/fneur.2020.556104. eCollection 2020.
citation: Mantegazza R, Wolfe GI, Muppidi S, Wiendl H, Fujita KP, O'Brien FL, Booth HDE, Howard JF Jr; REGAIN Study Group. Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension. Neurology. 2021 Jan 26;96(4):e610-e618. doi: 10.1212/WNL.0000000000011207. Epub 2020 Nov 23.
citation: Mantegazza R, O'Brien FL, Yountz M, Howard JF Jr; REGAIN study group. Consistent improvement with eculizumab across muscle groups in myasthenia gravis. Ann Clin Transl Neurol. 2020 Aug;7(8):1327-1339. doi: 10.1002/acn3.51121. Epub 2020 Jul 22.
citation: Jacob S, Murai H, Utsugisawa K, Nowak RJ, Wiendl H, Fujita KP, O'Brien F, Howard JF Jr. Response to eculizumab in patients with myasthenia gravis recently treated with chronic IVIg: a subgroup analysis of REGAIN and its open-label extension study. Ther Adv Neurol Disord. 2020 May 6;13:1756286420911784. doi: 10.1177/1756286420911784. eCollection 2020.
citation: Vissing J, Jacob S, Fujita KP, O'Brien F, Howard JF; REGAIN study group. 'Minimal symptom expression' in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab. J Neurol. 2020 Jul;267(7):1991-2001. doi: 10.1007/s00415-020-09770-y. Epub 2020 Mar 18.
citation: Andersen H, Mantegazza R, Wang JJ, O'Brien F, Patra K, Howard JF Jr; REGAIN Study Group. Eculizumab improves fatigue in refractory generalized myasthenia gravis. Qual Life Res. 2019 Aug;28(8):2247-2254. doi: 10.1007/s11136-019-02148-2. Epub 2019 Mar 23.