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Refractory Generalized Myasthenia GravisPhase 3NCT02301624

Extension Study of ECU-MG-301 to Evaluate Safety and Efficacy of Eculizumab in Refractory Generalized Myasthenia Gravis

A Phase 3 study testing Eculizumab in people with Refractory Generalized Myasthenia Gravis, run by Alexion Pharmaceuticals, Inc. at 60 sites in 17 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

To evaluate the safety and efficacy of eculizumab in the treatment of refractory generalized myasthenia gravis (gMG) as an extension study for the participants who previously completed Study ECU-MG-301(NCT01997229). 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
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
117 participants
Where
60 sitesin 17 countries
Study dates
12 Nov 2014to 15 Jan 2019
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

  • Participant has completed Study ECU-MG-301.
  • Participant has given written informed consent.
  • Participant was willing and able to comply with the protocol requirements for the duration of the study.
  • Female participant of childbearing potential must have had a negative pregnancy test (serum human chorionic gonadotropin). All participants were required to practice an effective, reliable, and medically approved contraceptive regimen during the study and for up to 5 months following discontinuation of treatment.

Who cannot join

  • Participants who withdrew from Study ECU-MG-301 as a result of an adverse event related to study drug.
  • Female participants who were pregnant, breastfeeding, or intended to conceive during the course of the study.
  • Unresolved meningococcal infection
  • Hypersensitivity to murine proteins or to one of the excipients of eculizumab
  • Any medical condition or circumstances that, in the opinion of the investigator, might have interfered with the participant's participation in the study, posed any added risk for the participant, or confounded the assessment of the participants.

Trial locations and contacts

60 sites in 17 countries.

60 sites in 17 countries

United States26 sites

  • Study site

    Baltimore, Maryland, 21201-1595

  • Study site

    Baltimore, Maryland, 21287-0876

  • Study site

    Birmingham, Alabama, 35233

  • Study site

    Boston, Massachusetts, 02115

  • Study site

    Burlington, Massachusetts, 01805

  • Study site

    Burlington, Vermont, 05401

  • Study site

    Chapel Hill, North Carolina, 27599

  • Study site

    Charlotte, North Carolina, 28207

  • Study site

    Columbus, Ohio, 43210

  • Study site

    Durham, North Carolina, 27710

  • Study site

    Indianapolis, Indiana, 46202

  • Study site

    Iowa City, Iowa, 52242

  • Study site

    Jacksonville, Florida, 32209

  • Study site

    Kansas City, Kansas, 66160

  • Study site

    Las Vegas, Nevada, 89145

  • Study site

    Los Angeles, California, 90033

  • Study site

    Miami, Florida, 33136

  • Study site

    New Haven, Connecticut, 06519

  • Study site

    Orange, California, 92868

  • Study site

    Palo Alto, California, 94304

  • Study site

    Portland, Oregon, 97239

  • Study site

    San Antonio, Texas, 78229

  • Study site

    San Francisco, California, 94115

  • Study site

    Seattle, Washington, 98195

  • Study site

    Springfield, Illinois, 62702

  • Study site

    Tampa, Florida, 33612

Other trials in United States

Japan8 sites

  • Study site

    Chiba

  • Study site

    Fukuoka

  • Study site

    Hanamaki

  • Study site

    Hokkaido

  • Study site

    Miyagi

  • Study site

    Nagasaki

  • Study site

    Osaka

  • Study site

    Osaka-Fu

Other trials in Japan

Belgium3 sites

  • Study site

    Edegem

  • Study site

    Ghent

  • Study site

    Leuven

Other trials in Belgium

Italy3 sites

  • Study site

    Milan

  • Study site

    Naples

  • Study site

    Roma

Other trials in Italy

Turkey (Türkiye)3 sites

  • Study site

    Ankara

  • Study site

    Izmir

  • Study site

    Kocaeli

Other trials in Turkey (Türkiye)

United Kingdom3 sites

  • Study site

    Birmingham

  • Study site

    Liverpool

  • Study site

    London

Other trials in United Kingdom

Czechia2 sites

  • Study site

    Ostrava - Poruba

  • Study site

    Prague

Other trials in Czechia

Denmark2 sites

  • Study site

    Arhus C

  • Study site

    Copenhagen

Other trials in Denmark

Spain2 sites

  • Study site

    Barcelona

  • Study site

    Madrid

Other trials in Spain

Argentina1 site

  • Study site

    Buenos Aires

Other trials in Argentina

Brazil1 site

  • Study site

    São Paulo

Other trials in Brazil

Canada1 site

  • Study site

    Edmonton

Other trials in Canada

Finland1 site

  • Study site

    Turku

Other trials in Finland

Hungary1 site

  • Study site

    Szeged

Other trials in Hungary

Netherlands1 site

  • Study site

    Amsterdam

Other trials in Netherlands

South Korea1 site

  • Study site

    Seoul

Other trials in South Korea

Sweden1 site

  • Study site

    Stockholm

Other trials in Sweden

About this study

Official title: A Phase III, Open-label Extension Trial of ECU-MG-301 to Evaluate the Safety and Efficacy of Eculizumab in Subjects With Refractory Generalized Myasthenia Gravis (gMG)

To evaluate the safety and efficacy of eculizumab in the treatment of refractory generalized myasthenia gravis (gMG) as an extension study for the participants who previously completed Study ECU-MG-301(NCT01997229).

Read the detailed description

ECU-MG-302 was an extension study designed to provide the participants who completed Study ECU-MG-301 an opportunity to receive eculizumab and collect clinical data to provide long-term safety and efficacy information on eculizumab in participants with refractory gMG.

After receiving blinded study treatment (eculizumab or placebo) in Study ECU-MG-301 for 26 weeks, participants were eligible to enroll in the ECU-MG-302 extension study. Participants were to enter Study ECU-MG-302 within 2 weeks after completing their Week 26 visit in Study ECU-MG-301.

Study ECU-MG-302 consisted of a 4-week Blind Induction Phase to preserve the blinded nature of Study ECU-MG-301, an Open-Label Maintenance Phase (up to 4 years), and a Safety Follow-up visit 8 weeks after the last dose for participants who withdrew from the study or discontinued eculizumab treatment at any time and for any reason after receiving any amount of eculizumab.

Being tested
Eculizumab, Placebo
Keywords
gMG, Myasthenia Gravis, 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

    Intravenous administration of eculizumab.

  • PlaceboDrug

    Intravenous administration of matching placebo. Participants received placebo only during the Blind Induction Phase.

Study groups in NCT02301624
Study groupRoleWhat they receive
Eculizumab/EculizumabExperimentalBlind Induction Phase: Participants who had received blinded treatment with eculizumab in Study ECU-MG-301 were administered eculizumab (4 vials/1200 milligrams [mg]) on Day 1 and Week 2 and placebo (4 vials/0 mg) at Weeks 1 and 3. Open-Label Maintenance Phase: Participants received open-label eculizumab (4 vials/1200 mg) every 2 weeks starting at Week 4 and continued throughout the study. Eculizumab 1200 mg was administered for up to 4 years in this extension study.
Receives: Biological: Eculizumab; Drug: Placebo
Placebo/EculizumabExperimentalBlind Induction Phase: Participants who had received blinded treatment with placebo in Study ECU-MG-301 were administered eculizumab/placebo (3 vials/900 mg, plus 1 vial/0 mg, respectively) on Day 1 and Weeks 1 through 3. Open-Label Maintenance Phase: Participants received open-label eculizumab (4 vials/1200 mg) every 2 weeks starting at Week 4 and continued throughout the study. Eculizumab 1200 mg was administered for up to 4 years in this extension study.
Receives: Biological: Eculizumab; Drug: Placebo

What is being measured

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

  1. Count Of Participants With Treatment-Emergent Adverse Events

    Treatment-emergent adverse events (TEAEs) are adverse events with onset on or after the first study drug dose in Study ECU-MG-302. Likewise, treatment-emergent serious adverse events (TESAEs) are serious adverse events that onset on or after the first study drug dose in Study ECU-MG-302. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.

    Measured: Day 1 (after dosing) through End of Study (Week 208)

Secondary outcomes (1)

  1. Change From Baseline In Myasthenia Gravis Activities Of Daily Living Profile (MG-ADL) Total Score At Week 4 And Week 130

    The MG-ADL scale is a validated 8-item patient-reported outcome measure. Participants assessed their functional disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb impairment (2 items). These 8 items were not weighted and were individually graded from 0 (normal) to 3 (most severe), providing a total MG-ADL score ranging from 0 to 24 points. A reduction in score indicates improvement in condition. Baseline was defined as the last available assessment prior to treatment (first study drug infusion) with eculizumab in Study ECU-MG-302. Change from Baseline in MG-ADL total score at Week 4 (blind induction phase) and at Week 130 (open-label eculizumab phase) are presented.

    Measured: Baseline, Week 4 and Week 130

Timeline

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

  1. First posted26 Nov 2014 (estimated)
  2. Study start12 Nov 2014
  3. Primary completion15 Jan 2019
  4. Study completion15 Jan 2019

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
Non-randomised
Intervention model
Parallel groups
Model description
Following the Blind Induction Phase, all participants received open-label eculizumab.
Masking
None (open label)
Enrolment
117 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02301624
Sponsor's protocol ID
ECU-MG-302
Other IDs
2013-002191-41
Status last verified
Jan 2020
First submitted
22 Nov 2014
Last updated
5 Feb 2020
Data monitoring committee
No

Publications

  • Muppidi S, Utsugisawa K, Benatar M, Murai H, Barohn RJ, Illa I, Jacob S, Vissing J, Burns TM, Kissel JT, Nowak RJ, Andersen H, Casasnovas C, de Bleecker JL, Vu TH, Mantegazza R, O'Brien FL, Wang JJ, Fujita KP, Howard JF Jr; Regain Study Group. Long-term safety and efficacy of eculizumab in generalized myasthenia gravis. Muscle Nerve. 2019 Jul;60(1):14-24. doi: 10.1002/mus.26447. Epub 2019 Mar 8.

    PubMed 30767274

  • Andersen H, Mantegazza R, Wang JJ, O'Brien F, Patra K, Howard JF Jr; REGAIN Study Group. Correction to: Eculizumab improves fatigue in refractory generalized myasthenia gravis. Qual Life Res. 2019 Aug;28(8):2255. doi: 10.1007/s11136-019-02204-x.

    PubMed 31115842

  • 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

  • Murai H, Uzawa A, Suzuki Y, Imai T, Shiraishi H, Suzuki H, Okumura M, O'Brien F, Wang JJ, Fujita KP, Utsugisawa K; REGAIN Study Group. Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis: A subgroup analysis of the REGAIN open-label extension study. J Neurol Sci. 2019 Dec 15;407:116419. doi: 10.1016/j.jns.2019.08.004. Epub 2019 Aug 3.

    PubMed 31698177

  • 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

  • Murai H, Suzuki S, Hasebe M, Fukamizu Y, Rodrigues E, Utsugisawa K. Safety and effectiveness of eculizumab in Japanese patients with generalized myasthenia gravis: interim analysis of post-marketing surveillance. Ther Adv Neurol Disord. 2021 Mar 16;14:17562864211001995. doi: 10.1177/17562864211001995. eCollection 2021.

    PubMed 33796147

  • 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

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 60 sites in 17 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 4 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 5 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 60 sites in United States, Japan, Belgium, Italy, Turkey (Türkiye) and 12 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. 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 5 Feb 2020). 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?

Count Of Participants With Treatment-Emergent Adverse Events (time frame: Day 1 (after dosing) through End of Study (Week 208)). 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 NCT02301624, which also lists 11 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 5 Feb 2020.

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