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

Refractory Generalized Myasthenia Gravis Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02301624
• Other study ID #: ECU-MG-302
• Secondary ID: 2013-002191-41
• Status: Completed
• Phase: Phase 3
• Start date: November 12, 2014
• Est. completion date: January 15, 2019

Study information

• Verified date: January 2020
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 117
• Est. completion date: January 15, 2019
• Est. primary completion date: January 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Muscle Weakness
• Myasthenia Gravis
• Refractory Generalized Myasthenia Gravis

Intervention

Biological:
• Eculizumab
Intravenous administration of eculizumab.

Drug:
• Placebo
Intravenous administration of matching placebo. Participants received placebo only during the Blind Induction Phase.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Czechia,  Denmark,  Finland,  Hungary,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Spain,  Sweden,  Turkey,  United Kingdom, 

References & Publications (4)

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. — View 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. E — View 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 s — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 1 (after dosing) through End of Study (Week 208)
Secondary	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.	Baseline, Week 4 and Week 130