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

NCT ID: NCT01997229

Last Updated: 2019-07-16

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

125 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-12-31

Study Completion Date

2016-06-30

Brief Summary

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

Detailed Description

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Conditions

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Refractory Generalized Myasthenia Gravis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Eculizumab

Biological/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).

Group Type EXPERIMENTAL

Eculizumab

Intervention Type BIOLOGICAL

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

Placebo

Placebo 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).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo

Interventions

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Eculizumab

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

Intervention Type BIOLOGICAL

Placebo

Placebo

Intervention Type DRUG

Eligibility Criteria

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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

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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

University of California San Francisco-Fresno

Fresno, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

University of California-Irvine

Orange, California, United States

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University of California Davis Health System

Sacramento, California, United States

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California Pacific Medical Center

San Francisco, California, United States

Site Status

Stanford University School of Medicine

Stanford, California, United States

Site Status

Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

University of Florida Health Science Center

Jacksonville, Florida, United States

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University of Miami School of Medicine

Miami, Florida, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

Georgia Regents University

Augusta, Georgia, United States

Site Status

Medical Associates of North Georgia

Canton, Georgia, United States

Site Status

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

University of Iowa College of Medicine

Iowa City, Iowa, United States

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University of Kansas Medical Center

Kansas City, Kansas, United States

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University of Maryland Medical Center

Baltimore, Maryland, United States

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Johns Hopkins University School Of Medicine

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Lahey Clinic Inc.

Burlington, Massachusetts, United States

Site Status

Wayne State University School of Medicine

Detroit, Michigan, United States

Site Status

Las Vegas Clinic

Las Vegas, Nevada, United States

Site Status

Buffalo General Hospital

Buffalo, New York, United States

Site Status

Hospital For Special Surgery/New York Presbyterian Hospital Cornell Campus

New York, New York, United States

Site Status

Mount Sinai School of Medicine

New York, New York, United States

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University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

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Carolinas Healthcare System

Charlotte, North Carolina, United States

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Duke University Health System

Durham, North Carolina, United States

Site Status

Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

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University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Wesley Neurology Clinic

Cordova, Tennessee, United States

Site Status

Vanderbilt Medical Center

Nashville, Tennessee, United States

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UT Southwestern

Dallas, Texas, United States

Site Status

Methodist Neurological Institute

Houston, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

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University of Vermont Medical Center

Burlington, Vermont, United States

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University of Washington

Seattle, Washington, United States

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Hospital Italiano

Ciudad Autonoma, Buenos Aires, Argentina

Site Status

Instituto de Investigaciones Neurologicas Raul Carrea, FLENI

Ciudad Autonoma, Buenos Aires, Argentina

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St Vincent's Hospital Melbourne

Fitzroy, Victoria, Australia

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Royal Perth Hospital

Perth, Western Australia, Australia

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UZ Antwerpen

Edegem, , Belgium

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AZ Sint-Lucas - Campus Sint-Lucas

Ghent, , Belgium

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UZ Leuven

Leuven, , Belgium

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Hospital Mãe de Deus

Porto Alegre, Rio Grande do Sul, Brazil

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Faculdade de Medicina do ABC

Santo André, São Paulo, Brazil

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Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, São Paulo, Brazil

Site Status

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

Rio de Janeiro, , Brazil

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UNIFESP - Universidade Federal de São Paulo

São Paulo, , Brazil

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University of Alberta Hospital

Edmonton, Alberta, Canada

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Toronto General Hospital

Toronto, Ontario, Canada

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Montreal Neurological Institute

Montreal, Quebec, Canada

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Vseobecna fakultni nemocnice v Praze

Prague, Prague, Czechia

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Fakultni nemocnice Brno

Brno, , Czechia

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Fakultni nemocnice Ostrava

Ostrava - Poruba, , Czechia

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Århus Universitetshospital

Aarhus C, , Denmark

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Rigshospitalet

København Ø, , Denmark

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Helsingin yliopistollinen keskussairaala

Helsinki, , Finland

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Neuro NEO Oy

Turku, , Finland

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CHU de Nice Hôpital Pasteur 2

Nice, Alpes Maritimes, France

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Groupe Hospitalier Pellegrin - Hôpital Pellegrin

Bordeaux, Gironde, France

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Hopital Roger Salengro - CHU Lille

Lille, Nord, France

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Hopital Neurologique Pierre Wertheimer

Bron, Rhone, France

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LMU-Campus Innenstadt

Munich, Bavaria, Germany

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Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

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Navy Hospital of Athens

Athens, , Greece

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General Hospital of Thessaloniki "G. Papanikolaou"

Thessaloniki, , Greece

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Jahn Ferenc Del-Pesti Korhaz

Budapest, , Hungary

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

Szeged, , Hungary

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Policlinico di Catania

Catania, , Italy

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Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, , Italy

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Azienda Ospedaliera Universitaria "Federico II"

Napoli, , Italy

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Ospedale San Camillo IRCCS

Padua, , Italy

Site Status

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

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

Roma, , Italy

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Policlinico Universitario Agostino Gemelli

Roma, , Italy

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Azienda Ospedaliera Sant'Andrea - Università di Roma La Sapienza

Roma, , Italy

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Ospedale Santa Chiara

Trento, , Italy

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Chiba University Hospital

Chiba, Chiba, Japan

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Kyushu University Hospital

Fukuoka, Fukuoka, Japan

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Sapporo Medical University Hospital

Sapporo, Hokkaido, Japan

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Hanamaki General Hospitals

Hanamaki-shi, Iwate, Japan

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NHO Sendai Medical Center

Sendai, Miyagi, Japan

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NHO Nagasaki Kawatana Medical Center

Kawatana, Nagasaki, Japan

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Nagasaki University Hospital

Nagasaki, Nagasaki, Japan

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Kinki University Hospital

Osakasayama-shi, Osaka, Japan

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Osaka University Hospital

Suita-shi, Osaka, Japan

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Toho University Ohashi Medical Center

Meguro-ku, Tokyo-To, Japan

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Yamaguchi University Hospital

Ube-shi, Yamaguchi, Japan

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Academisch Medisch Centrum

Amsterdam, , Netherlands

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Leiden Universitair Medisch Centrum

Leiden, , Netherlands

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Maastricht University Medical Center

Maastricht, , Netherlands

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Severance Hospital, Yonsei University Health System

Seoul, , South Korea

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Samsung Medical Center

Seoul, , South Korea

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Korea University Anam Hospital

Seoul, , South Korea

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Seoul Metropolitan Government Seoul National University

Seoul, , South Korea

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Hospital Universitari Vall d'Hebron

Barcelona, , Spain

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Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

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Hospital Universitari de Bellvitge

Barcelona, , Spain

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Hospital Universitario La Paz

Madrid, , Spain

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Sahlgrenska Sjukhuset

Gothenburg, , Sweden

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Karolinska Universitetssjukhuset - Solna

Stockholm, , Sweden

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Hacettepe University Medical Faculty

Ankara, , Turkey (Türkiye)

Site Status

Karadeniz Tecnical Uni. Med. Fac.

Istanbul, , Turkey (Türkiye)

Site Status

Dokuz Eylul University Medicine Faculty

Izmir, , Turkey (Türkiye)

Site Status

Kocaeli University Medical Faculty

Kocaeli, , Turkey (Türkiye)

Site Status

Ondokuz Mayıs University of Medicine

Samsun, , Turkey (Türkiye)

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The Walton Centre

Liverpool, Merseyside, United Kingdom

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Queen Elizabeth Hospital

Birmingham, West Midlands, United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

Countries

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United States Argentina Australia Belgium Brazil Canada Czechia Denmark Finland France Germany Greece Hungary Italy Japan Netherlands South Korea Spain Sweden Turkey (Türkiye) United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 23512355 (View on PubMed)

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.

Reference Type RESULT
PMID: 29066163 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34795626 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34590717 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33329303 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33229455 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32700461 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32426038 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32189108 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30905021 (View on PubMed)

Related Links

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http://www.alexionclinicaltrials.com

Alexion Clinical Trials Webpage

Other Identifiers

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2013-003589-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ECU-MG-301

Identifier Type: -

Identifier Source: org_study_id

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