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

Primary Purpose

Refractory Generalized Myasthenia Gravis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Eculizumab
Placebo
Sponsored by
Alexion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory Generalized Myasthenia Gravis focused on measuring gMG, Myasthenia Gravis, safety, efficacy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Eculizumab/Eculizumab

Placebo/Eculizumab

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
November 22, 2014
Last Updated
January 27, 2020
Sponsor
Alexion
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1. Study Identification

Unique Protocol Identification Number
NCT02301624
Brief Title
Extension Study of ECU-MG-301 to Evaluate Safety and Efficacy of Eculizumab in Refractory Generalized Myasthenia Gravis
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)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
November 12, 2014 (Actual)
Primary Completion Date
January 15, 2019 (Actual)
Study Completion Date
January 15, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alexion

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Generalized Myasthenia Gravis
Keywords
gMG, Myasthenia Gravis, safety, efficacy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Following the Blind Induction Phase, all participants received open-label eculizumab.
Masking
None (Open Label)
Masking Description
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.
Allocation
Non-Randomized
Enrollment
117 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Eculizumab/Eculizumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo/Eculizumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Eculizumab
Intervention Description
Intravenous administration of eculizumab.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Intravenous administration of matching placebo. Participants received placebo only during the Blind Induction Phase.
Primary Outcome Measure Information:
Title
Count Of Participants With Treatment-Emergent Adverse Events
Description
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.
Time Frame
Day 1 (after dosing) through End of Study (Week 208)
Secondary Outcome Measure Information:
Title
Change From Baseline In Myasthenia Gravis Activities Of Daily Living Profile (MG-ADL) Total Score At Week 4 And Week 130
Description
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.
Time Frame
Baseline, Week 4 and Week 130

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marcus Yountz, MD
Organizational Affiliation
Alexion
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62702
Country
United States
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201-1595
Country
United States
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287-0876
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89145
Country
United States
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28207
Country
United States
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
City
Buenos Aires
Country
Argentina
City
Edegem
Country
Belgium
City
Gent
Country
Belgium
City
Leuven
Country
Belgium
City
São Paulo
Country
Brazil
City
Edmonton
Country
Canada
City
Ostrava - Poruba
Country
Czechia
City
Praha 2
Country
Czechia
City
Arhus C
Country
Denmark
City
Kobenhavn
Country
Denmark
City
Turku
Country
Finland
City
Szeged
Country
Hungary
City
Milano
Country
Italy
City
Napoli
Country
Italy
City
Roma
Country
Italy
City
Chiba
Country
Japan
City
Fukuoka
Country
Japan
City
Hanamaki
Country
Japan
City
Hokkaido
Country
Japan
City
Miyagi
Country
Japan
City
Nagasaki
Country
Japan
City
Osaka-Fu
Country
Japan
City
Osaka
Country
Japan
City
Seoul
Country
Korea, Republic of
City
Amsterdam
Country
Netherlands
City
Barcelona
Country
Spain
City
Madrid
Country
Spain
City
Stockholm
Country
Sweden
City
Ankara
Country
Turkey
City
İzmir
Country
Turkey
City
Kocaeli
Country
Turkey
City
Birmingham
Country
United Kingdom
City
Liverpool
Country
United Kingdom
City
London
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
30767274
Citation
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.
Results Reference
result
PubMed Identifier
31115842
Citation
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.
Results Reference
result
PubMed Identifier
30905021
Citation
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. Erratum In: Qual Life Res. 2019 May 21;:
Results Reference
result
PubMed Identifier
31698177
Citation
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.
Results Reference
result
PubMed Identifier
34590717
Citation
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.
Results Reference
derived
PubMed Identifier
33796147
Citation
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. Erratum In: Ther Adv Neurol Disord. 2021 Oct 29;14:17562864211049696.
Results Reference
derived
PubMed Identifier
33329303
Citation
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.
Results Reference
derived
PubMed Identifier
33229455
Citation
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.
Results Reference
derived
PubMed Identifier
32700461
Citation
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.
Results Reference
derived
PubMed Identifier
32426038
Citation
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.
Results Reference
derived
PubMed Identifier
32189108
Citation
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.
Results Reference
derived

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

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