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

Phase 3
Completed
Conditions
Refractory Generalized Myasthenia Gravis
Interventions
Biological: Eculizumab
Drug: Placebo
Registration Number
NCT01997229
Lead Sponsor
Alexion Pharmaceuticals, Inc.
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
125
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
EculizumabEculizumabBiological/Vaccine: Eculizumab; Induction phase: 3 vials of study drug (equivalent to 900 mg of eculizumab) weekly for 4 doses (every 7 days ± 2 days) followed by 4 vials of study drug (equivalent to 1200 mg of eculizumab) 1 week later for the fifth dose (Week 4); Maintenance phase: 4 vials of study drug (equivalent to 1200 mg of eculizumab) every 2 weeks (14 days ± 2 days) from the fifth dose onwards (Week 6 through Week 26).
PlaceboPlaceboPlacebo contains the same buffer components without the active ingredient; Induction phase: 3 vials of study drug (placebo) weekly for 4 doses (every 7 days ± 2 days) followed by 4 vials of study drug (placebo) 1 week later for the fifth dose (Week 4); Maintenance phase: 4 vials of study drug (placebo) every 2 weeks (14 days ± 2 days) from the fifth dose onwards (Week 6 through Week 26).
Primary Outcome Measures
NameTimeMethod
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)End of study (Week 26)

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).

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (114)

University of Alabama

🇺🇸

Birmingham, Alabama, United States

University of California San Francisco-Fresno

🇺🇸

Fresno, California, United States

University of California-Irvine

🇺🇸

Orange, California, United States

University of Florida Health Science Center

🇺🇸

Jacksonville, Florida, United States

University of California Davis Health System

🇺🇸

Sacramento, California, United States

Yale New Haven Hospital

🇺🇸

New Haven, Connecticut, United States

Stanford University School of Medicine

🇺🇸

Stanford, California, United States

University of South Florida

🇺🇸

Tampa, Florida, United States

Georgia Regents University

🇺🇸

Augusta, Georgia, United States

Medical Associates of North Georgia

🇺🇸

Canton, Georgia, United States

University of Iowa College of Medicine

🇺🇸

Iowa City, Iowa, United States

Southern Illinois University School of Medicine

🇺🇸

Springfield, Illinois, United States

University of Maryland Medical Center

🇺🇸

Baltimore, Maryland, United States

Johns Hopkins University School Of Medicine

🇺🇸

Baltimore, Maryland, United States

Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

Lahey Clinic Inc.

🇺🇸

Burlington, Massachusetts, United States

Wayne State University School of Medicine

🇺🇸

Detroit, Michigan, United States

Buffalo General Hospital

🇺🇸

Buffalo, New York, 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 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

Oregon Health & Science University

🇺🇸

Portland, Oregon, United States

University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

Wesley Neurology Clinic

🇺🇸

Cordova, Tennessee, United States

UT Southwestern

🇺🇸

Dallas, Texas, United States

University of Vermont Medical Center

🇺🇸

Burlington, Vermont, United States

University of Southern California

🇺🇸

Los Angeles, California, United States

Hospital Italiano

🇦🇷

Ciudad Autonoma, Buenos Aires, Argentina

Instituto de Investigaciones Neurologicas Raul Carrea, FLENI

🇦🇷

Ciudad Autonoma, Buenos Aires, Argentina

Toho University Ohashi Medical Center

🇯🇵

Meguro-ku, Tokyo-To, Japan

UZ Antwerpen

🇧🇪

Edegem, Belgium

St Vincent's Hospital Melbourne

🇦🇺

Fitzroy, Victoria, Australia

AZ Sint-Lucas - Campus Sint-Lucas

🇧🇪

Gent, Belgium

Faculdade de Medicina do ABC

🇧🇷

Santo André, Sao Paulo, Brazil

UZ Leuven

🇧🇪

Leuven, Belgium

HUCFF-UFRJ - Hospital Universitário Clementino Fraga Filho - Universidade Federal do Rio de Janeiro

🇧🇷

Rio De Janeiro, Brazil

Fundação Faculdade Regional de Medicina de São José do Rio Preto

🇧🇷

São José do Rio Preto, Sao Paulo, Brazil

University of Alberta Hospital

🇨🇦

Edmonton, Alberta, Canada

UNIFESP - Universidade Federal de São Paulo

🇧🇷

São Paulo, Brazil

Toronto General Hospital

🇨🇦

Toronto, Ontario, Canada

Vseobecna fakultni nemocnice v Praze

🇨🇿

Praha, Prague, Czechia

Montreal Neurological Institute

🇨🇦

Montreal, Quebec, Canada

Fakultni nemocnice Ostrava

🇨🇿

Ostrava - Poruba, Czechia

CHU de Nice Hôpital Pasteur 2

🇫🇷

Nice Cedex 3, Alpes Maritimes, France

Helsingin yliopistollinen keskussairaala

🇫🇮

Helsinki, Finland

Neuro NEO Oy

🇫🇮

Turku, Finland

Groupe Hospitalier Pellegrin - Hôpital Pellegrin

🇫🇷

Bordeaux Cedex, Gironde, France

Medizinische Hochschule Hannover

🇩🇪

Hannover, Niedersachsen, Germany

Hopital Roger Salengro - CHU Lille

🇫🇷

Lille Cedex, Nord, France

Hopital Neurologique Pierre Wertheimer

🇫🇷

Bron cedex, Rhone, France

LMU-Campus Innenstadt

🇩🇪

Muenchen, Bayern, Germany

Navy Hospital of Athens

🇬🇷

Athens, Greece

Jahn Ferenc Del-Pesti Korhaz

🇭🇺

Budapest, Hungary

General Hospital of Thessaloniki "G. Papanikolaou"

🇬🇷

Thessaloniki, Greece

Ospedale San Camillo IRCCS

🇮🇹

Padova, Italy

Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin. Közp.

🇭🇺

Szeged, Hungary

Policlinico di Catania

🇮🇹

Catania, Italy

Umberto I Pol. di Roma-Università di Roma La Sapienza

🇮🇹

Roma, Italy

Azienda Ospedaliero Universitaria Pisana

🇮🇹

Pisa, Italy

Fondazione IRCCS Istituto Neurologico Carlo Besta

🇮🇹

Milano, Italy

Azienda Ospedaliera Universitaria "Federico II"

🇮🇹

Napoli, Italy

Policlinico Universitario Agostino Gemelli

🇮🇹

Roma, Italy

Azienda Ospedaliera Sant'Andrea - Università di Roma La Sapienza

🇮🇹

Roma, Italy

Chiba University Hospital

🇯🇵

Chiba-shi, Chiba-Ken, Japan

Kyushu University Hospital

🇯🇵

Fukuoka-shi, Fukuoka-Ken, Japan

Ospedale Santa Chiara

🇮🇹

Trento, Italy

Osaka University Hospital

🇯🇵

Suita-shi, Osaka-Fu, Japan

Hanamaki General Hospitals

🇯🇵

Hanamaki-shi, Iwate-Ken, Japan

NHO Sendai Medical Center

🇯🇵

Sendai-shi, Miyagi-Ken, Japan

Kinki University Hospital

🇯🇵

Osakasayama-shi, Osaka-Fu, Japan

Sapporo Medical University Hospital

🇯🇵

Sapporo-shi, Hokkaido, Japan

NHO Nagasaki Kawatana Medical Center

🇯🇵

Kawatana, Nagasaki-Ken, Japan

Nagasaki University Hospital

🇯🇵

Nagasaki-shi, Nagasaki-Ken, Japan

Yamaguchi University Hospital

🇯🇵

Ube-shi, Yamaguchi-Ken, Japan

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Korea University Anam Hospital

🇰🇷

Seoul, Korea, Republic of

Seoul Metropolitan Government Seoul National University

🇰🇷

Seoul, Korea, Republic of

Severance Hospital, Yonsei University Health System

🇰🇷

Seoul, Korea, Republic of

Academisch Medisch Centrum

🇳🇱

Amsterdam, Netherlands

Hospital Universitario La Paz

🇪🇸

Madrid, Spain

Leiden Universitair Medisch Centrum

🇳🇱

Leiden, Netherlands

Hospital Universitari de Bellvitge

🇪🇸

Barcelona, Spain

Hospital Universitari Vall d'Hebron

🇪🇸

Barcelona, Spain

Sahlgrenska Sjukhuset

🇸🇪

Göteborg, Sweden

Maastricht University Medical Center

🇳🇱

Maastricht, Netherlands

Karolinska Universitetssjukhuset - Solna

🇸🇪

Stockholm, Sweden

Hospital de la Santa Creu i Sant Pau

🇪🇸

Barcelona, Spain

Dokuz Eylul University Medicine Faculty

🇹🇷

Izmir, Turkey

King's College Hospital

🇬🇧

London, United Kingdom

Hacettepe University Medical Faculty

🇹🇷

Ankara, Turkey

Karadeniz Tecnical Uni. Med. Fac.

🇹🇷

Istanbul, Turkey

Kocaeli University Medical Faculty

🇹🇷

Kocaeli, Turkey

Ondokuz Mayıs University of Medicine

🇹🇷

Samsun, Turkey

The Walton Centre

🇬🇧

Liverpool, Merseyside, United Kingdom

Queen Elizabeth Hospital

🇬🇧

Birmingham, West Midlands, United Kingdom

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Methodist Neurological Institute

🇺🇸

Houston, Texas, United States

University of Washington

🇺🇸

Seattle, Washington, United States

University of Miami School of Medicine

🇺🇸

Miami, Florida, United States

Indiana University

🇺🇸

Indianapolis, Indiana, United States

Las Vegas Clinic

🇺🇸

Las Vegas, Nevada, United States

Fakultni nemocnice Brno

🇨🇿

Brno, Czechia

Hospital Mãe de Deus

🇧🇷

Porto Alegre, Rio Grande Do Sul, Brazil

Royal Perth Hospital

🇦🇺

Perth, Western Australia, Australia

Vanderbilt Medical Center

🇺🇸

Nashville, Tennessee, United States

California Pacific Medical Center

🇺🇸

San Francisco, California, United States

Duke University Health System

🇺🇸

Durham, North Carolina, United States

University of Texas Health Science Center at San Antonio

🇺🇸

San Antonio, Texas, United States

Århus Universitetshospital

🇩🇰

Aarhus C, Denmark

Rigshospitalet

🇩🇰

København Ø, Denmark

University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

Rhode Island Hospital

🇺🇸

Providence, Rhode Island, United States

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