Safety and Efficacy of Eculizumab in Refractory Generalized Myasthenia Gravis (REGAIN Study)

Refractory Generalized Myasthenia Gravis Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01997229
• Other study ID #: ECU-MG-301
• Secondary ID: 2013-003589-15
• Status: Completed
• Phase: Phase 3
• Start date: December 2013
• Est. completion date: June 2016

Study information

• Verified date: July 2019
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: June 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Muscle Weakness
• Myasthenia Gravis
• Refractory Generalized Myasthenia Gravis

Intervention

Biological:
• Eculizumab
Induction Phase: 900 mg IV weekly X 4 Maintenance Phase: 1200 mg IV every 2 weeks during Weeks 4-26

Drug:
• Placebo
Placebo

Locations

Country	Name	City	State
Argentina	Hospital Italiano	Ciudad Autonoma	Buenos Aires
Argentina	Instituto de Investigaciones Neurologicas Raul Carrea, FLENI	Ciudad Autonoma	Buenos Aires
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Belgium	UZ Antwerpen	Edegem
Belgium	AZ Sint-Lucas - Campus Sint-Lucas	Gent
Belgium	UZ Leuven	Leuven
Brazil	Hospital Mãe de Deus	Porto Alegre	Rio Grande Do Sul
Brazil	HUCFF-UFRJ - Hospital Universitário Clementino Fraga Filho - Universidade Federal do Rio de Janeiro	Rio De Janeiro
Brazil	Faculdade de Medicina do ABC	Santo André	Sao Paulo
Brazil	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São José do Rio Preto	Sao Paulo
Brazil	UNIFESP - Universidade Federal de São Paulo	São Paulo
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Montreal Neurological Institute	Montreal	Quebec
Canada	Toronto General Hospital	Toronto	Ontario
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice Ostrava	Ostrava - Poruba
Czechia	Vseobecna fakultni nemocnice v Praze	Praha	Prague
Denmark	Århus Universitetshospital	Aarhus C
Denmark	Rigshospitalet	København Ø
Finland	Helsingin yliopistollinen keskussairaala	Helsinki
Finland	Neuro NEO Oy	Turku
France	Groupe Hospitalier Pellegrin - Hôpital Pellegrin	Bordeaux Cedex	Gironde
France	Hopital Neurologique Pierre Wertheimer	Bron cedex	Rhone
France	Hopital Roger Salengro - CHU Lille	Lille Cedex	Nord
France	CHU de Nice Hôpital Pasteur 2	Nice Cedex 3	Alpes Maritimes
Germany	Medizinische Hochschule Hannover	Hannover	Niedersachsen
Germany	LMU-Campus Innenstadt	Muenchen	Bayern
Greece	Navy Hospital of Athens	Athens
Greece	General Hospital of Thessaloniki "G. Papanikolaou"	Thessaloniki
Hungary	Jahn Ferenc Del-Pesti Korhaz	Budapest
Hungary	Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin. Közp.	Szeged
Italy	Policlinico di Catania	Catania
Italy	Fondazione IRCCS Istituto Neurologico Carlo Besta	Milano
Italy	Azienda Ospedaliera Universitaria "Federico II"	Napoli
Italy	Ospedale San Camillo IRCCS	Padova
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Azienda Ospedaliera Sant'Andrea - Università di Roma La Sapienza	Roma
Italy	Policlinico Universitario Agostino Gemelli	Roma
Italy	Umberto I Pol. di Roma-Università di Roma La Sapienza	Roma
Italy	Ospedale Santa Chiara	Trento
Japan	Chiba University Hospital	Chiba-shi	Chiba-Ken
Japan	Kyushu University Hospital	Fukuoka-shi	Fukuoka-Ken
Japan	Hanamaki General Hospitals	Hanamaki-shi	Iwate-Ken
Japan	NHO Nagasaki Kawatana Medical Center	Kawatana	Nagasaki-Ken
Japan	Toho University Ohashi Medical Center	Meguro-ku	Tokyo-To
Japan	Nagasaki University Hospital	Nagasaki-shi	Nagasaki-Ken
Japan	Kinki University Hospital	Osakasayama-shi	Osaka-Fu
Japan	Sapporo Medical University Hospital	Sapporo-shi	Hokkaido
Japan	NHO Sendai Medical Center	Sendai-shi	Miyagi-Ken
Japan	Osaka University Hospital	Suita-shi	Osaka-Fu
Japan	Yamaguchi University Hospital	Ube-shi	Yamaguchi-Ken
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul Metropolitan Government Seoul National University	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	Leiden Universitair Medisch Centrum	Leiden
Netherlands	Maastricht University Medical Center	Maastricht
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari de Bellvitge	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Sweden	Sahlgrenska Sjukhuset	Göteborg
Sweden	Karolinska Universitetssjukhuset - Solna	Stockholm
Turkey	Hacettepe University Medical Faculty	Ankara
Turkey	Karadeniz Tecnical Uni. Med. Fac.	Istanbul
Turkey	Dokuz Eylul University Medicine Faculty	Izmir
Turkey	Kocaeli University Medical Faculty	Kocaeli
Turkey	Ondokuz Mayis University of Medicine	Samsun
United Kingdom	Queen Elizabeth Hospital	Birmingham	West Midlands
United Kingdom	The Walton Centre	Liverpool	Merseyside
United Kingdom	King's College Hospital	London
United States	Georgia Regents University	Augusta	Georgia
United States	Johns Hopkins University School Of Medicine	Baltimore	Maryland
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	University of Alabama	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Buffalo General Hospital	Buffalo	New York
United States	Lahey Clinic Inc.	Burlington	Massachusetts
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Medical Associates of North Georgia	Canton	Georgia
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Carolinas Healthcare System	Charlotte	North Carolina
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Wesley Neurology Clinic	Cordova	Tennessee
United States	UT Southwestern	Dallas	Texas
United States	Wayne State University School of Medicine	Detroit	Michigan
United States	Duke University Health System	Durham	North Carolina
United States	University of California San Francisco-Fresno	Fresno	California
United States	Methodist Neurological Institute	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Iowa College of Medicine	Iowa City	Iowa
United States	University of Florida Health Science Center	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Las Vegas Clinic	Las Vegas	Nevada
United States	University of Southern California	Los Angeles	California
United States	University of Miami School of Medicine	Miami	Florida
United States	Vanderbilt Medical Center	Nashville	Tennessee
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Hospital For Special Surgery/New York Presbyterian Hospital Cornell Campus	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	University of California-Irvine	Orange	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	University of California Davis Health System	Sacramento	California
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	California Pacific Medical Center	San Francisco	California
United States	University of Washington	Seattle	Washington
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Stanford University School of Medicine	Stanford	California
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Czechia,  Denmark,  Finland,  France,  Germany,  Greece,  Hungary,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Spain,  Sweden,  Turkey,  United Kingdom, 

References & Publications (2)

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. — View 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 antibod — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	In the Worst-Rank analysis, the 125 total patients were ranked from best outcome (rank/score of 1) to worst outcome (rank/score of 125).	End of study (Week 26)

External Links

•   Alexion Clinical Trials Webpage