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

NCT01997229 | Completed Phase 3 Results

• 2 other identifiers: ECU-MG-3012013-003589-15
• Study Type: interventional
• Target: 125
• Locations: 21 countries
• Sites: 114

Brief Summary

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

Conditions

Refractory Generalized Myasthenia Gravis

Keywords

Myasthenia Gravis; Eculizumab; safety; efficacy

Outcome Measures

Primary Outcomes (1)

• 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)

Study Arms (2)

Eculizumab

EXPERIMENTAL

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).

Biological: Eculizumab

Placebo

PLACEBO COMPARATOR

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).

Drug: Placebo

Interventions

Eculizumab BIOLOGICAL

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

Eculizumab

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥18 years old
• Diagnosis of MG made by the following tests:
• Positive serologic test for anti-AChR Abs as confirmed at screening, and
• One of the following:
• History of abnormal neuromuscular transmission test demonstrated by single-fiber electromyography (SFEMG) or repetitive nerve stimulation, or
• History of positive anticholinesterase test, e.g. edrophonium chloride test, or
• 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:
• Failed treatment with at least two immunosuppressive agents. Or,
• Failed treatment with at least one immunosuppressive agent and require chronic plasma exchange or IVIg

You may not qualify if:

• 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)

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (114)

University of Alabama

Birmingham, Alabama, 35233, United States

Location

University of California San Francisco-Fresno

Fresno, California, 93720, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

University of California-Irvine

Orange, California, 92868, United States

Location

University of California Davis Health System

Sacramento, California, 95765, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

University of Florida Health Science Center

Jacksonville, Florida, 32209, United States

Location

University of Miami School of Medicine

Miami, Florida, 33136, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Georgia Regents University

Augusta, Georgia, 30912, United States

Location

Medical Associates of North Georgia

Canton, Georgia, 30114, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa College of Medicine

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University School Of Medicine

Baltimore, Maryland, 21287-0876, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Lahey Clinic Inc.

Burlington, Massachusetts, 01805, United States

Location

Wayne State University School of Medicine

Detroit, Michigan, 48201, United States

Location

Las Vegas Clinic

Las Vegas, Nevada, 89145, United States

Location

Buffalo General Hospital

Buffalo, New York, 14203, United States

Location

Hospital For Special Surgery/New York Presbyterian Hospital Cornell Campus

New York, New York, 10021, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Carolinas Healthcare System

Charlotte, North Carolina, 28207, United States

Location

Duke University Health System

Durham, North Carolina, 27705, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02905, United States

Location

Wesley Neurology Clinic

Cordova, Tennessee, 38018, United States

Location

Vanderbilt Medical Center

Nashville, Tennessee, 37232, United States

Location

UT Southwestern

Dallas, Texas, 75390, United States

Location

Methodist Neurological Institute

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05405, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Hospital Italiano

Ciudad Autonoma, Buenos Aires, 1181, Argentina

Location

Instituto de Investigaciones Neurologicas Raul Carrea, FLENI

Ciudad Autonoma, Buenos Aires, C1428AQK, Argentina

Location

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

AZ Sint-Lucas - Campus Sint-Lucas

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Hospital Mãe de Deus

Porto Alegre, Rio Grande do Sul, 90110-270, Brazil

Location

Faculdade de Medicina do ABC

Santo André, São Paulo, Postal Code: 09060-650, Brazil

Location

Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

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

Rio de Janeiro, 21941-913, Brazil

Location

UNIFESP - Universidade Federal de São Paulo

São Paulo, 04037-002, Brazil

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Montreal Neurological Institute

Montreal, Quebec, H3A 2B4, Canada

Location

Vseobecna fakultni nemocnice v Praze

Prague, Prague, 120 00, Czechia

Location

Fakultni nemocnice Brno

Brno, 625 00, Czechia

Location

Fakultni nemocnice Ostrava

Ostrava - Poruba, 708 52, Czechia

Location

Århus Universitetshospital

Aarhus C, 8000, Denmark

Location

Rigshospitalet

København Ø, 2100, Denmark

Location

Helsingin yliopistollinen keskussairaala

Helsinki, 00290, Finland

Location

Neuro NEO Oy

Turku, 20520, Finland

Location

CHU de Nice Hôpital Pasteur 2

Nice, Alpes Maritimes, 06202, France

Location

Groupe Hospitalier Pellegrin - Hôpital Pellegrin

Bordeaux, Gironde, 33000, France

Location

Hopital Roger Salengro - CHU Lille

Lille, Nord, 59037, France

Location

Hopital Neurologique Pierre Wertheimer

Bron, Rhone, 69677, France

Location

LMU-Campus Innenstadt

Munich, Bavaria, 80336, Germany

Location

Medizinische Hochschule Hannover

Hanover, Lower Saxony, 30625, Germany

Location

Navy Hospital of Athens

Athens, 11521, Greece

Location

General Hospital of Thessaloniki "G. Papanikolaou"

Thessaloniki, 57010, Greece

Location

Jahn Ferenc Del-Pesti Korhaz

Budapest, 1204, Hungary

Location

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

Szeged, 6725, Hungary

Location

Policlinico di Catania

Catania, 95123, Italy

Location

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, 20133, Italy

Location

Azienda Ospedaliera Universitaria "Federico II"

Napoli, 80131, Italy

Location

Ospedale San Camillo IRCCS

Padua, 35128, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126, Italy

Location

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

Roma, 00161, Italy

Location

Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

Location

Azienda Ospedaliera Sant'Andrea - Università di Roma La Sapienza

Roma, 00189, Italy

Location

Ospedale Santa Chiara

Trento, 38122, Italy

Location

Chiba University Hospital

Chiba, Chiba, 260-8677, Japan

Location

Kyushu University Hospital

Fukuoka, Fukuoka, 812-8582, Japan

Location

Sapporo Medical University Hospital

Sapporo, Hokkaido, 060-8543, Japan

Location

Hanamaki General Hospitals

Hanamaki-shi, Iwate, 025-0075, Japan

Location

NHO Sendai Medical Center

Sendai, Miyagi, 983-8520, Japan

Location

NHO Nagasaki Kawatana Medical Center

Kawatana, Nagasaki, 859-3615, Japan

Location

Nagasaki University Hospital

Nagasaki, Nagasaki, 852-8501, Japan

Location

Kinki University Hospital

Osakasayama-shi, Osaka, 589-8511, Japan

Location

Osaka University Hospital

Suita-shi, Osaka, 565-0871, Japan

Location

Toho University Ohashi Medical Center

Meguro-ku, Tokyo-To, 153-8515, Japan

Location

Yamaguchi University Hospital

Ube-shi, Yamaguchi, 755-8505, Japan

Location

Academisch Medisch Centrum

Amsterdam, 1105 AZ, Netherlands

Location

Leiden Universitair Medisch Centrum

Leiden, 2333 ZA, Netherlands

Location

Maastricht University Medical Center

Maastricht, 6229 HX, Netherlands

Location

Severance Hospital, Yonsei University Health System

Seoul, 120-752, South Korea

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Korea University Anam Hospital

Seoul, 136-705, South Korea

Location

Seoul Metropolitan Government Seoul National University

Seoul, 156707, South Korea

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitari de Bellvitge

Barcelona, 08907, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Sahlgrenska Sjukhuset

Gothenburg, 41345, Sweden

Location

Karolinska Universitetssjukhuset - Solna

Stockholm, 17176, Sweden

Location

Hacettepe University Medical Faculty

Ankara, 06100, Turkey (Türkiye)

Location

Karadeniz Tecnical Uni. Med. Fac.

Istanbul, 61080, Turkey (Türkiye)

Location

Dokuz Eylul University Medicine Faculty

Izmir, 35340, Turkey (Türkiye)

Location

Kocaeli University Medical Faculty

Kocaeli, 41380, Turkey (Türkiye)

Location

Ondokuz Mayıs University of Medicine

Samsun, 55139, Turkey (Türkiye)

Location

The Walton Centre

Liverpool, Merseyside, L9 7LJ, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, West Midlands, B15 2WB, United Kingdom

Location

King's College Hospital

London, SE5 9NU, United Kingdom

Location

Related Publications (10)

• 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.

  PMID: 23512355 BACKGROUND

• 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.

  PMID: 29066163 RESULT

• 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.

  PMID: 34795626 DERIVED

• 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.

  PMID: 34590717 DERIVED

• 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.

  PMID: 33329303 DERIVED

• 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.

  PMID: 33229455 DERIVED

• 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.

  PMID: 32700461 DERIVED

• 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.

  PMID: 32426038 DERIVED

• 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.

  PMID: 32189108 DERIVED

• 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.

  PMID: 30905021 DERIVED

Related Links

• Alexion Clinical Trials Webpage

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

eculizumab

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Jing-Jing Wang, MD
• Organization: Alexion Pharmaceuticals, Inc.

JingJing.Wang@alexion.com

+1 (475) 230-2596

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2013
• First Posted: November 28, 2013
• Study Start: December 1, 2013
• Primary Completion: February 1, 2016
• Study Completion: June 1, 2016
• Last Updated: July 16, 2019
• Results First Posted: February 7, 2018

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

AR (2); IT (9); CA (3); DK (2); NL (3); BE (3); ES (4); TU (5); CZ (3); FR (4); GB (3); US (41); FI (2); DE (2); JP (11); AU (2); SE (2); BR (5); GR (2); HU (2); KR (4)