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Refractory Generalized Myasthenia GravisPhase 3NCT01997229

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

A Phase 3 study testing Eculizumab in people with Refractory Generalized Myasthenia Gravis, run by Alexion Pharmaceuticals, Inc. at 114 sites in 21 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Refractory Generalized Myasthenia Gravis
What is being tested?
Eculizumab
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
125 participants
Where
114 sitesin 21 countries
Study dates
Dec 2013to Jun 2016
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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

Who cannot join

  • 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)

Trial locations and contacts

114 sites in 21 countries.

114 sites in 21 countries

United States41 sites

  • Georgia Regents University

    Augusta, Georgia, 30912

  • University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • Johns Hopkins University School Of Medicine

    Baltimore, Maryland, 21287-0876

  • University of Alabama

    Birmingham, Alabama, 35233

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Buffalo General Hospital

    Buffalo, New York, 14203

  • Lahey Clinic Inc.

    Burlington, Massachusetts, 01805

  • University of Vermont Medical Center

    Burlington, Vermont, 05405

  • Medical Associates of North Georgia

    Canton, Georgia, 30114

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Carolinas Healthcare System

    Charlotte, North Carolina, 28207

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

  • Wesley Neurology Clinic

    Cordova, Tennessee, 38018

  • UT Southwestern

    Dallas, Texas, 75390

  • Wayne State University School of Medicine

    Detroit, Michigan, 48201

  • Duke University Health System

    Durham, North Carolina, 27705

  • University of California San Francisco-Fresno

    Fresno, California, 93720

  • Methodist Neurological Institute

    Houston, Texas, 77030

  • Indiana University

    Indianapolis, Indiana, 46202

  • University of Iowa College of Medicine

    Iowa City, Iowa, 52242

  • University of Florida Health Science Center

    Jacksonville, Florida, 32209

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Las Vegas Clinic

    Las Vegas, Nevada, 89145

  • University of Southern California

    Los Angeles, California, 90033

  • University of Miami School of Medicine

    Miami, Florida, 33136

  • Vanderbilt Medical Center

    Nashville, Tennessee, 37232

  • Yale New Haven Hospital

    New Haven, Connecticut, 06510

  • Hospital For Special Surgery/New York Presbyterian Hospital Cornell Campus

    New York, New York, 10021

  • Mount Sinai School of Medicine

    New York, New York, 10029

  • University of California-Irvine

    Orange, California, 92868

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • Rhode Island Hospital

    Providence, Rhode Island, 02905

  • University of California Davis Health System

    Sacramento, California, 95765

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • California Pacific Medical Center

    San Francisco, California, 94115

  • University of Washington

    Seattle, Washington, 98195

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62702

  • Stanford University School of Medicine

    Stanford, California, 94305

  • University of South Florida

    Tampa, Florida, 33612

Other trials in United States

Japan11 sites

  • Chiba University Hospital

    Chiba, Chiba, 260-8677

  • Kyushu University Hospital

    Fukuoka, Fukuoka, 812-8582

  • Hanamaki General Hospitals

    Hanamaki-shi, Iwate, 025-0075

  • NHO Nagasaki Kawatana Medical Center

    Kawatana, Nagasaki, 859-3615

  • Toho University Ohashi Medical Center

    Meguro-ku, Tokyo-To, 153-8515

  • Nagasaki University Hospital

    Nagasaki, Nagasaki, 852-8501

  • Kinki University Hospital

    Osakasayama-shi, Osaka, 589-8511

  • Sapporo Medical University Hospital

    Sapporo, Hokkaido, 060-8543

  • NHO Sendai Medical Center

    Sendai, Miyagi, 983-8520

  • Osaka University Hospital

    Suita-shi, Osaka, 565-0871

  • Yamaguchi University Hospital

    Ube-shi, Yamaguchi, 755-8505

Other trials in Japan

Italy9 sites

  • Policlinico di Catania

    Catania, 95123

  • Fondazione IRCCS Istituto Neurologico Carlo Besta

    Milan, 20133

  • Azienda Ospedaliera Universitaria "Federico II"

    Naples, 80131

  • Ospedale San Camillo IRCCS

    Padova, 35128

  • Azienda Ospedaliero Universitaria Pisana

    Pisa, 56126

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

    Roma, 00161

  • Policlinico Universitario Agostino Gemelli

    Roma, 00168

  • Azienda Ospedaliera Sant'Andrea - Università di Roma La Sapienza

    Roma, 00189

  • Ospedale Santa Chiara

    Trento, 38122

Other trials in Italy

Brazil5 sites

  • Hospital Mãe de Deus

    Porto Alegre, Rio Grande do Sul, 90110-270

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

    Rio de Janeiro, 21941-913

  • Faculdade de Medicina do ABC

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

  • Fundação Faculdade Regional de Medicina de São José do Rio Preto

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

  • UNIFESP - Universidade Federal de São Paulo

    São Paulo, 04037-002

Other trials in Brazil

Turkey (Türkiye)5 sites

  • Hacettepe University Medical Faculty

    Ankara, 06100

  • Karadeniz Tecnical Uni. Med. Fac.

    Istanbul, 61080

  • Dokuz Eylul University Medicine Faculty

    Izmir, 35340

  • Kocaeli University Medical Faculty

    Kocaeli, 41380

  • Ondokuz Mayıs University of Medicine

    Samsun, 55139

Other trials in Turkey (Türkiye)

France4 sites

  • Groupe Hospitalier Pellegrin - Hôpital Pellegrin

    Bordeaux, Gironde, 33000

  • Hopital Neurologique Pierre Wertheimer

    Bron, Rhone, 69677

  • Hopital Roger Salengro - CHU Lille

    Lille, Nord, 59037

  • CHU de Nice Hôpital Pasteur 2

    Nice, Alpes Maritimes, 06202

Other trials in France

South Korea4 sites

  • Severance Hospital, Yonsei University Health System

    Seoul, 120-752

  • Samsung Medical Center

    Seoul, 135-710

  • Korea University Anam Hospital

    Seoul, 136-705

  • Seoul Metropolitan Government Seoul National University

    Seoul, 156707

Other trials in South Korea

Spain4 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, 08041

  • Hospital Universitari de Bellvitge

    Barcelona, 08907

  • Hospital Universitario La Paz

    Madrid, 28046

Other trials in Spain

Belgium3 sites

  • UZ Antwerpen

    Edegem, 2650

  • AZ Sint-Lucas - Campus Sint-Lucas

    Ghent, 9000

  • UZ Leuven

    Leuven, 3000

Other trials in Belgium

Canada3 sites

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 2B7

  • Montreal Neurological Institute

    Montreal, Quebec, H3A 2B4

  • Toronto General Hospital

    Toronto, Ontario, M5G 2C4

Other trials in Canada

Czechia3 sites

  • Fakultni nemocnice Brno

    Brno, 625 00

  • Fakultni nemocnice Ostrava

    Ostrava - Poruba, 708 52

  • Vseobecna fakultni nemocnice v Praze

    Prague, Prague, 120 00

Other trials in Czechia

Netherlands3 sites

  • Academisch Medisch Centrum

    Amsterdam, 1105 AZ

  • Leiden Universitair Medisch Centrum

    Leiden, 2333 ZA

  • Maastricht University Medical Center

    Maastricht, 6229 HX

Other trials in Netherlands

United Kingdom3 sites

  • Queen Elizabeth Hospital

    Birmingham, West Midlands, B15 2WB

  • The Walton Centre

    Liverpool, Merseyside, L9 7LJ

  • King's College Hospital

    London, SE5 9NU

Other trials in United Kingdom

Argentina2 sites

  • Hospital Italiano

    Ciudad Autonoma, Buenos Aires, 1181

  • Instituto de Investigaciones Neurologicas Raul Carrea, FLENI

    Ciudad Autonoma, Buenos Aires, C1428AQK

Other trials in Argentina

Australia2 sites

  • St Vincent's Hospital Melbourne

    Fitzroy, Victoria, 3065

  • Royal Perth Hospital

    Perth, Western Australia, 6000

Other trials in Australia

Denmark2 sites

  • Århus Universitetshospital

    Aarhus C, 8000

  • Rigshospitalet

    København Ø, 2100

Other trials in Denmark

Finland2 sites

  • Helsingin yliopistollinen keskussairaala

    Helsinki, 00290

  • Neuro NEO Oy

    Turku, 20520

Other trials in Finland

Germany2 sites

  • Medizinische Hochschule Hannover

    Hanover, Lower Saxony, 30625

  • LMU-Campus Innenstadt

    Munich, Bavaria, 80336

Other trials in Germany

Greece2 sites

  • Navy Hospital of Athens

    Athens, 11521

  • General Hospital of Thessaloniki "G. Papanikolaou"

    Thessaloniki, 57010

Other trials in Greece

Hungary2 sites

  • Jahn Ferenc Del-Pesti Korhaz

    Budapest, 1204

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

    Szeged, 6725

Other trials in Hungary

Sweden2 sites

  • Sahlgrenska Sjukhuset

    Gothenburg, 41345

  • Karolinska Universitetssjukhuset - Solna

    Stockholm, 17176

Other trials in Sweden

About this 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)

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

Being tested
Eculizumab, Placebo
Keywords
Myasthenia Gravis, Eculizumab, safety, efficacy
Medical subject headings
Myasthenia Gravis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EculizumabBiological

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

  • PlaceboDrug

    Placebo

Study groups in NCT01997229
Study groupRoleWhat they receive
EculizumabExperimentalBiological/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).
Receives: Biological: Eculizumab
PlaceboPlacebo comparatorPlacebo 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).
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: End of study (Week 26)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Nov 2013 (estimated)
  2. Study startDec 2013
  3. Primary completionFeb 2016
  4. Study completionJun 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
125 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01997229
Sponsor's protocol ID
ECU-MG-301
Other IDs
2013-003589-15
Status last verified
Jul 2019
First submitted
18 Nov 2013
Last updated
16 Jul 2019
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 23512355

  • 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.

    PubMed 29066163

  • 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.

    PubMed 34795626

  • 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.

    PubMed 34590717

  • 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.

    PubMed 33329303

  • 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.

    PubMed 33229455

  • 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.

    PubMed 32700461

  • 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.

    PubMed 32426038

  • 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.

    PubMed 32189108

  • 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.

    PubMed 30905021

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Eculizumab in people with Refractory Generalized Myasthenia Gravis, run by Alexion Pharmaceuticals, Inc. at 114 sites in 21 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 114 sites in United States, Japan, Italy, Brazil, Turkey (Türkiye) and 16 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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) (time frame: End of study (Week 26)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01997229, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2019.

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