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

NCT ID: NCT02301624

Last Updated: 2020-02-05

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

117 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-11-12

Study Completion Date

2019-01-15

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Refractory Generalized Myasthenia Gravis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Following the Blind Induction Phase, all participants received open-label eculizumab.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

The study consisted of a 4-week Blind Induction Phase to preserve the blinded nature of Study ECU-MG-301, followed by an Open-Label Maintenance Phase.

Study Groups

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Eculizumab/Eculizumab

Blind 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.

Group Type EXPERIMENTAL

Eculizumab

Intervention Type BIOLOGICAL

Intravenous administration of eculizumab.

Placebo

Intervention Type DRUG

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

Placebo/Eculizumab

Blind 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.

Group Type EXPERIMENTAL

Eculizumab

Intervention Type BIOLOGICAL

Intravenous administration of eculizumab.

Placebo

Intervention Type DRUG

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

Interventions

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Eculizumab

Intravenous administration of eculizumab.

Intervention Type BIOLOGICAL

Placebo

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Participant has completed Study ECU-MG-301.
2. Participant has given written informed consent.
3. Participant was willing and able to comply with the protocol requirements for the duration of the study.
4. 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.

Exclusion Criteria

1. Participants who withdrew from Study ECU-MG-301 as a result of an adverse event related to study drug.
2. Female participants who were pregnant, breastfeeding, or intended to conceive during the course of the study.
3. Unresolved meningococcal infection
4. Hypersensitivity to murine proteins or to one of the excipients of eculizumab
5. 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.
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

Principal Investigators

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Marcus Yountz, MD

Role: STUDY_DIRECTOR

Alexion Pharmaceuticals, Inc.

Locations

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Birmingham, Alabama, United States

Site Status

Los Angeles, California, United States

Site Status

Orange, California, United States

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Palo Alto, California, United States

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San Francisco, California, United States

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New Haven, Connecticut, United States

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Jacksonville, Florida, United States

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Miami, Florida, United States

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Tampa, Florida, United States

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Springfield, Illinois, United States

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Indianapolis, Indiana, United States

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Iowa City, Iowa, United States

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Kansas City, Kansas, United States

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Baltimore, Maryland, United States

Site Status

Baltimore, Maryland, United States

Site Status

Boston, Massachusetts, United States

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Burlington, Massachusetts, United States

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Las Vegas, Nevada, United States

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Chapel Hill, North Carolina, United States

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Charlotte, North Carolina, United States

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Durham, North Carolina, United States

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Columbus, Ohio, United States

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Portland, Oregon, United States

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San Antonio, Texas, United States

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Burlington, Vermont, United States

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Seattle, Washington, United States

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Buenos Aires, , Argentina

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Edegem, , Belgium

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Ghent, , Belgium

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Leuven, , Belgium

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São Paulo, , Brazil

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Edmonton, , Canada

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Ostrava - Poruba, , Czechia

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Prague, , Czechia

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Arhus C, , Denmark

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Copenhagen, , Denmark

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Turku, , Finland

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Szeged, , Hungary

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Milan, , Italy

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Napoli, , Italy

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Roma, , Italy

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Chiba, , Japan

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Fukuoka, , Japan

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Hanamaki, , Japan

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Hokkaido, , Japan

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Miyagi, , Japan

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Nagasaki, , Japan

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Osaka, , Japan

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Osaka-Fu, , Japan

Site Status

Amsterdam, , Netherlands

Site Status

Seoul, , South Korea

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Barcelona, , Spain

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Madrid, , Spain

Site Status

Stockholm, , Sweden

Site Status

Ankara, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

Site Status

Kocaeli, , Turkey (Türkiye)

Site Status

Birmingham, , United Kingdom

Site Status

Liverpool, , United Kingdom

Site Status

London, , United Kingdom

Site Status

Countries

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

References

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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.

Reference Type RESULT
PMID: 30767274 (View on PubMed)

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.

Reference Type RESULT
PMID: 31115842 (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 RESULT
PMID: 30905021 (View on PubMed)

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.

Reference Type RESULT
PMID: 31698177 (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)

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.

Reference Type DERIVED
PMID: 33796147 (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)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2013-002191-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ECU-MG-302

Identifier Type: -

Identifier Source: org_study_id

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