Clinical trial NCT02301624: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Refractory Generalized Myasthenia Gravis
Keywords: gMG
Myasthenia Gravis
safety
efficacy
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-11-26
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Following the Blind Induction Phase, all participants received open-label eculizumab.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Count Of Participants With Treatment-Emergent Adverse Events
timeFrame: Day 1 (after dosing) through End of Study (Week 208)
Secondary outcomes:
measure: Change From Baseline In Myasthenia Gravis Activities Of Daily Living Profile (MG-ADL) Total Score At Week 4 And Week 130
timeFrame: Baseline, Week 4 and Week 130
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Los Angeles
country: United States
state: California
city: Orange
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: San Francisco
country: United States
state: California
city: New Haven
country: United States
state: Connecticut
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Springfield
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Iowa City
country: United States
state: Iowa
city: Kansas City
country: United States
state: Kansas
city: Baltimore
country: United States
state: Maryland
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Burlington
country: United States
state: Massachusetts
city: Las Vegas
country: United States
state: Nevada
city: Chapel Hill
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Columbus
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: San Antonio
country: United States
state: Texas
city: Burlington
country: United States
state: Vermont
city: Seattle
country: United States
state: Washington
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
Study officials:
affiliation: Alexion Pharmaceuticals, Inc.
name: Marcus Yountz, MD
role: STUDY_DIRECTOR
References:
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.