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

• Sponsor: Alexion Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02301624
• Collaborator: (none)
• Enrollment: 117
• Locations: 60
• Arms: 2
• Actual Duration (Months): 50.1
• Patients Per Site: 2
• Patients Per Site Per Month: 0

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Refractory Generalized Myasthenia Gravis	Biological: Eculizumab; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 117 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Following the Blind Induction Phase, all participants received open-label eculizumab.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.
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Nov 12, 2014
• Actual Primary Completion Date: Jan 15, 2019
• Actual Study Completion Date: Jan 15, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: Eculizumab; Intravenous administration of eculizumab.; Drug: Placebo; Intravenous administration of matching placebo. Participants received placebo only during the Blind Induction Phase.
Experimental: 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.	Biological: Eculizumab; Intravenous administration of eculizumab.; Drug: Placebo; Intravenous administration of matching placebo. Participants received placebo only during the Blind Induction Phase.

Outcome Measures

Primary Outcome Measures

1. Count Of Participants With Treatment-Emergent Adverse Events [Day 1 (after dosing) through End of Study (Week 208)]

   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

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States	35233
2		Los Angeles	California	United States	90033
3		Orange	California	United States	92868
4		Palo Alto	California	United States	94304
5		San Francisco	California	United States	94115
6		New Haven	Connecticut	United States	06519
7		Jacksonville	Florida	United States	32209
8		Miami	Florida	United States	33136
9		Tampa	Florida	United States	33612
10		Springfield	Illinois	United States	62702
11		Indianapolis	Indiana	United States	46202
12		Iowa City	Iowa	United States	52242
13		Kansas City	Kansas	United States	66160
14		Baltimore	Maryland	United States	21201-1595
15		Baltimore	Maryland	United States	21287-0876
16		Boston	Massachusetts	United States	02115
17		Burlington	Massachusetts	United States	01805
18		Las Vegas	Nevada	United States	89145
19		Chapel Hill	North Carolina	United States	27599
20		Charlotte	North Carolina	United States	28207
21		Durham	North Carolina	United States	27710
22		Columbus	Ohio	United States	43210
23		Portland	Oregon	United States	97239
24		San Antonio	Texas	United States	78229
25		Burlington	Vermont	United States	05401
26		Seattle	Washington	United States	98195
27		Buenos Aires		Argentina
28		Edegem		Belgium
29		Gent		Belgium
30		Leuven		Belgium
31		São Paulo		Brazil
32		Edmonton		Canada
33		Ostrava - Poruba		Czechia
34		Praha 2		Czechia
35		Arhus C		Denmark
36		Kobenhavn		Denmark
37		Turku		Finland
38		Szeged		Hungary
39		Milano		Italy
40		Napoli		Italy
41		Roma		Italy
42		Chiba		Japan
43		Fukuoka		Japan
44		Hanamaki		Japan
45		Hokkaido		Japan
46		Miyagi		Japan
47		Nagasaki		Japan
48		Osaka-Fu		Japan
49		Osaka		Japan
50		Seoul		Korea, Republic of
51		Amsterdam		Netherlands
52		Barcelona		Spain
53		Madrid		Spain
54		Stockholm		Sweden
55		Ankara		Turkey
56		İzmir		Turkey
57		Kocaeli		Turkey
58		Birmingham		United Kingdom
59		Liverpool		United Kingdom
60		London		United Kingdom

Sponsors and Collaborators

• Alexion Pharmaceuticals

Investigators

• Study Director: Marcus Yountz, MD, Alexion Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Dec 19, 2016
• Statistical Analysis Plan - Feb 6, 2019

More Information

Publications

None provided.

• Responsible Party: Alexion Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02301624
• Other Study ID Numbers: ECU-MG-302; 2013-002191-41
• First Posted: Nov 26, 2014
• Last Update Posted: Feb 5, 2020
• Last Verified: Jan 1, 2020

• Keywords provided by Alexion Pharmaceuticals: gMG; Myasthenia Gravis; safety; efficacy
• Additional relevant MeSH terms: Myasthenia Gravis; Muscle Weakness; Eculizumab

Study Results

Participant Flow

Recruitment Details	Participants who completed Study ECU-MG-301 (NCT01997229) were eligible to participate in Study ECU-MG-302.

Arm/Group Title	Eculizumab/Eculizumab	Placebo/Eculizumab
Arm/Group 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.
Period Title: Blind Induction Phase
STARTED	56	61
Received at Least 1 Dose of Study Drug	56	61
COMPLETED	55	61
NOT COMPLETED	1	0
Period Title: Blind Induction Phase
STARTED	55	61
Received at Least 1 Dose of Study Drug	55	61
COMPLETED	43	44
NOT COMPLETED	12	17

Baseline Characteristics

Arm/Group Title	Eculizumab/Eculizumab	Placebo/Eculizumab	Total
Arm/Group Description	Blind Induction Phase: Participants who had received blinded treatment with eculizumab in Study ECU-MG-301 were administered eculizumab (4 vials/1200 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.	Total of all reporting groups
Overall Participants	56	61	117
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.2 (15.52)	47.5 (17.85)	47.4 (16.70)
Sex: Female, Male (Count of Participants)
Female	38 67.9%	41 67.2%	79 67.5%
Male	18 32.1%	20 32.8%	38 32.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 14.3%	10 16.4%	18 15.4%
Not Hispanic or Latino	45 80.4%	48 78.7%	93 79.5%
Unknown or Not Reported	3 5.4%	3 4.9%	6 5.1%
Race/Ethnicity, Customized (Count of Participants)
Asian	3 5.4%	16 26.2%	19 16.2%
Black or African American	0 0%	2 3.3%	2 1.7%
White	47 83.9%	41 67.2%	88 75.2%
Multiple	1 1.8%	0 0%	1 0.9%
Unknown	1 1.8%	0 0%	1 0.9%
Other	4 7.1%	2 3.3%	6 5.1%

Outcome Measures

1. Primary Outcome

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)

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of eculizumab in this extension study.

Arm/Group Title	Eculizumab/Eculizumab	Placebo/Eculizumab
Arm/Group Description	After receiving blinded treatment with eculizumab in Study ECU-MG-301 for 26 weeks, all participants received blinded study drug weekly for 4 weeks, then received open-label eculizumab 1200 mg every 2 weeks for up to 4 years in this extension study.	After receiving blinded treatment with placebo in Study ECU-MG-301 for 26 weeks, all participants received blinded study drug weekly for 4 weeks, then received open-label eculizumab 1200 mg every 2 weeks for up to 4 years in this extension study.
Measure Participants	56	61
TEAEs	55 98.2%	59 96.7%
TEAEs leading to withdrawal	3 5.4%	5 8.2%
TESAEs	30 53.6%	30 49.2%
TESAEs leading to withdrawal	3 5.4%	4 6.6%
Deaths	2 3.6%	1 1.6%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of eculizumab in this extension study and had an MG-ADL efficacy assessment after study drug infusion at the specified time points.

Arm/Group Title	Eculizumab/Eculizumab	Placebo/Eculizumab
Arm/Group Description	After receiving blinded treatment with eculizumab in Study ECU-MG-301 for 26 weeks, all participants received blinded study drug weekly for 4 weeks, then received open-label eculizumab 1200 mg every 2 weeks for up to 4 years in this extension study.	After receiving blinded treatment with placebo in Study ECU-MG-301 for 26 weeks, all participants received blinded study drug weekly for 4 weeks, then received open-label eculizumab 1200 mg every 2 weeks for up to 4 years in this extension study.
Measure Participants	55	61
Change from Baseline At Week 4 (Blind Induction)	-0.2 (1.77)	-2.4 (3.04)
Change from Baseline at Week 130 (Open-label)	-0.7 (4.19)	-3.9 (3.68)

Adverse Events

Time Frame	Day 1 after dosing of study drug through Week 208.
Adverse Event Reporting Description	All eligible enrolled participants who received at least 1 dose of study drug.
Arm/Group Title	Eculizumab/Eculizumab		Placebo/Eculizumab		Eculizumab (Combined Total)
Arm/Group Description	Blind Induction Phase: Participants who had received blinded treatment with eculizumab in Study ECU-MG-301 were administered eculizumab (4 vials/1200 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.		All participants who received at least 1 dose of eculizumab in the extension study. 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.
All Cause Mortality
	Eculizumab/Eculizumab		Placebo/Eculizumab		Eculizumab (Combined Total)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/56 (3.6%)		1/61 (1.6%)		3/117 (2.6%)
Serious Adverse Events
	Eculizumab/Eculizumab		Placebo/Eculizumab		Eculizumab (Combined Total)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/56 (53.6%)		30/61 (49.2%)		60/117 (51.3%)
Blood and lymphatic system disorders
Anaemia	2/56 (3.6%)		1/61 (1.6%)		3/117 (2.6%)
Disseminated intravascular coagulation	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Histiocytosis haematophagic	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Cardiac disorders
Acute myocardial infarction	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Aortic valve incompetence	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Atrial fibrillation	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Cardiogenic shock	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Myocardial infarction	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Ear and labyrinth disorders
Vertigo positional	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Gastrointestinal disorders
Abdominal incarcerated hernia	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Ascites	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Dyspepsia	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Gastritis	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Gastrointestinal haemorrhage	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Intestinal obstruction	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Large intestine polyp	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Pancreatitis acute	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Small intestinal obstruction	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Vomiting	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
General disorders
Asthenia	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Chest pain	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Pyrexia	3/56 (5.4%)		0/61 (0%)		3/117 (2.6%)
Hepatobiliary disorders
Chronic hepatic failure	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Hepatic failure	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Immune system disorders
Autoimmune disorder	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Infections and infestations
Appendicitis	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Aspergillus infection	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Asymptomatic bacteriuria	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Bronchitis	1/56 (1.8%)		1/61 (1.6%)		2/117 (1.7%)
Bursitis infective staphylococcal	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Cellulitis	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Colonic abscess	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Cytomegalovirus infection	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Device related sepsis	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Gastroenteritis	1/56 (1.8%)		2/61 (3.3%)		3/117 (2.6%)
Influenza	2/56 (3.6%)		0/61 (0%)		2/117 (1.7%)
Localised infection	1/56 (1.8%)		1/61 (1.6%)		2/117 (1.7%)
Meningitis meningococcal	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Periorbital cellulitis	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Pneumonia	2/56 (3.6%)		2/61 (3.3%)		4/117 (3.4%)
Pseudomonal sepsis	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Pseudomonas infection	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Rectal abscess	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Respiratory syncytial virus infection	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Sepsis	2/56 (3.6%)		1/61 (1.6%)		3/117 (2.6%)
Tonsillitis	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Upper respiratory tract infection	1/56 (1.8%)		1/61 (1.6%)		2/117 (1.7%)
Urinary tract infection	0/56 (0%)		2/61 (3.3%)		2/117 (1.7%)
Wound infection	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Injury, poisoning and procedural complications
Fall	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Fibula fracture	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Gastrostomy tube site complication	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Humerus fracture	2/56 (3.6%)		0/61 (0%)		2/117 (1.7%)
Infusion related reaction	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Procedural pain	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Rib fracture	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Spinal compression fracture	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Investigations
Haemoglobin decreased	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Metabolism and nutrition disorders
Central obesity	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Dehydration	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Hypoglycaemia	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Obesity	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Musculoskeletal and connective tissue disorders
Arthritis reactive	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Foot deformity	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Fracture nonunion	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Intervertebral disc protrusion	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Muscular weakness	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Myositis	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Pain in extremity	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Rhabdomyolysis	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Synovitis	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	1/56 (1.8%)		1/61 (1.6%)		2/117 (1.7%)
Lymphoma	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Malignant melanoma in situ	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Neuroendocrine carcinoma	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Prostate cancer	0/18 (0%)		1/20 (5%)		1/38 (2.6%)
Skin papilloma	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Nervous system disorders
Carotid artery stenosis	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Encephalopathy	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Headache	1/56 (1.8%)		2/61 (3.3%)		3/117 (2.6%)
Loss of consciousness	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Metabolic encephalopathy	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Myasthenia gravis	7/56 (12.5%)		9/61 (14.8%)		16/117 (13.7%)
Myasthenia gravis crisis	2/56 (3.6%)		2/61 (3.3%)		4/117 (3.4%)
Quadriparesis	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Syncope	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Psychiatric disorders
Depression	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Renal and urinary disorders
Acute kidney injury	1/56 (1.8%)		1/61 (1.6%)		2/117 (1.7%)
Nephrolithiasis	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Ureterolithiasis	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Reproductive system and breast disorders
Cervical dysplasia	0/38 (0%)		1/41 (2.4%)		1/79 (1.3%)
Ovarian cyst	1/38 (2.6%)		0/41 (0%)		1/79 (1.3%)
Vaginal haemorrhage	1/38 (2.6%)		0/41 (0%)		1/79 (1.3%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/56 (0%)		3/61 (4.9%)		3/117 (2.6%)
Chronic obstructive pulmonary disease	1/56 (1.8%)		0/61 (0%)		1/117 (0.9%)
Pneumonia aspiration	0/56 (0%)		2/61 (3.3%)		2/117 (1.7%)
Pulmonary congestion	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Pulmonary embolism	0/56 (0%)		3/61 (4.9%)		3/117 (2.6%)
Respiratory distress	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Respiratory failure	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Vascular disorders
Arterial occlusive disease	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Deep vein thrombosis	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Extremity necrosis	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Haematoma	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Lupus vasculitis	0/56 (0%)		1/61 (1.6%)		1/117 (0.9%)
Other (Not Including Serious) Adverse Events
	Eculizumab/Eculizumab		Placebo/Eculizumab		Eculizumab (Combined Total)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/56 (96.4%)		59/61 (96.7%)		113/117 (96.6%)
Blood and lymphatic system disorders
Anaemia	5/56 (8.9%)		3/61 (4.9%)		8/117 (6.8%)
Iron deficiency anaemia	3/56 (5.4%)		2/61 (3.3%)		5/117 (4.3%)
Lymphopenia	3/56 (5.4%)		0/61 (0%)		3/117 (2.6%)
Cardiac disorders
Atrial fibrillation	4/56 (7.1%)		1/61 (1.6%)		5/117 (4.3%)
Palpitations	1/56 (1.8%)		4/61 (6.6%)		5/117 (4.3%)
Tachycardia	4/56 (7.1%)		2/61 (3.3%)		6/117 (5.1%)
Ear and labyrinth disorders
Ear pain	2/56 (3.6%)		4/61 (6.6%)		6/117 (5.1%)
Vertigo	3/56 (5.4%)		4/61 (6.6%)		7/117 (6%)
Eye disorders
Cataract	4/56 (7.1%)		5/61 (8.2%)		9/117 (7.7%)
Dry eye	2/56 (3.6%)		4/61 (6.6%)		6/117 (5.1%)
Eye pain	0/56 (0%)		4/61 (6.6%)		4/117 (3.4%)
Gastrointestinal disorders
Abdominal discomfort	4/56 (7.1%)		6/61 (9.8%)		10/117 (8.5%)
Abdominal pain	3/56 (5.4%)		2/61 (3.3%)		5/117 (4.3%)
Abdominal pain upper	2/56 (3.6%)		6/61 (9.8%)		8/117 (6.8%)
Dental caries	2/56 (3.6%)		5/61 (8.2%)		7/117 (6%)
Diarrhoea	15/56 (26.8%)		14/61 (23%)		29/117 (24.8%)
Dyspepsia	2/56 (3.6%)		4/61 (6.6%)		6/117 (5.1%)
Nausea	9/56 (16.1%)		13/61 (21.3%)		22/117 (18.8%)
Tooth disorder	3/56 (5.4%)		0/61 (0%)		3/117 (2.6%)
Toothache	3/56 (5.4%)		5/61 (8.2%)		8/117 (6.8%)
Vomiting	3/56 (5.4%)		7/61 (11.5%)		10/117 (8.5%)
General disorders
Chest pain	4/56 (7.1%)		2/61 (3.3%)		6/117 (5.1%)
Fatigue	8/56 (14.3%)		7/61 (11.5%)		15/117 (12.8%)
Influenza like illness	4/56 (7.1%)		3/61 (4.9%)		7/117 (6%)
Oedema peripheral	4/56 (7.1%)		3/61 (4.9%)		7/117 (6%)
Peripheral swelling	3/56 (5.4%)		2/61 (3.3%)		5/117 (4.3%)
Pyrexia	5/56 (8.9%)		8/61 (13.1%)		13/117 (11.1%)
Immune system disorders
Seasonal allergy	3/56 (5.4%)		7/61 (11.5%)		10/117 (8.5%)
Infections and infestations
Bronchitis	6/56 (10.7%)		7/61 (11.5%)		13/117 (11.1%)
Cellulitis	4/56 (7.1%)		4/61 (6.6%)		8/117 (6.8%)
Gastroenteritis	6/56 (10.7%)		5/61 (8.2%)		11/117 (9.4%)
Gastroenteritis viral	4/56 (7.1%)		6/61 (9.8%)		10/117 (8.5%)
Herpes zoster	3/56 (5.4%)		1/61 (1.6%)		4/117 (3.4%)
Influenza	11/56 (19.6%)		10/61 (16.4%)		21/117 (17.9%)
Nasopharyngitis	20/56 (35.7%)		22/61 (36.1%)		42/117 (35.9%)
Oral herpes	3/56 (5.4%)		3/61 (4.9%)		6/117 (5.1%)
Pharyngitis	3/56 (5.4%)		0/61 (0%)		3/117 (2.6%)
Pneumonia	4/56 (7.1%)		6/61 (9.8%)		10/117 (8.5%)
Respiratory tract infection	4/56 (7.1%)		0/61 (0%)		4/117 (3.4%)
Sinusitis	7/56 (12.5%)		4/61 (6.6%)		11/117 (9.4%)
Tonsillitis	1/56 (1.8%)		4/61 (6.6%)		5/117 (4.3%)
Upper respiratory tract infection	12/56 (21.4%)		15/61 (24.6%)		27/117 (23.1%)
Urinary tract infection	10/56 (17.9%)		8/61 (13.1%)		18/117 (15.4%)
Injury, poisoning and procedural complications
Contusion	7/56 (12.5%)		5/61 (8.2%)		12/117 (10.3%)
Fall	8/56 (14.3%)		6/61 (9.8%)		14/117 (12%)
Infusion related reaction	4/56 (7.1%)		7/61 (11.5%)		11/117 (9.4%)
Ligament sprain	3/56 (5.4%)		2/61 (3.3%)		5/117 (4.3%)
Procedural pain	2/56 (3.6%)		4/61 (6.6%)		6/117 (5.1%)
Rib fracture	3/56 (5.4%)		0/61 (0%)		3/117 (2.6%)
Tooth fracture	3/56 (5.4%)		1/61 (1.6%)		4/117 (3.4%)
Metabolism and nutrition disorders
Dehydration	3/56 (5.4%)		1/61 (1.6%)		4/117 (3.4%)
Vitamin D deficiency	3/56 (5.4%)		2/61 (3.3%)		5/117 (4.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	11/56 (19.6%)		12/61 (19.7%)		23/117 (19.7%)
Back pain	5/56 (8.9%)		7/61 (11.5%)		12/117 (10.3%)
Muscle spasms	5/56 (8.9%)		6/61 (9.8%)		11/117 (9.4%)
Musculoskeletal pain	3/56 (5.4%)		4/61 (6.6%)		7/117 (6%)
Myalgia	5/56 (8.9%)		7/61 (11.5%)		12/117 (10.3%)
Neck pain	5/56 (8.9%)		4/61 (6.6%)		9/117 (7.7%)
Pain in extremity	9/56 (16.1%)		8/61 (13.1%)		17/117 (14.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	2/56 (3.6%)		4/61 (6.6%)		6/117 (5.1%)
Nervous system disorders
Dizziness	3/56 (5.4%)		6/61 (9.8%)		9/117 (7.7%)
Headache	20/56 (35.7%)		24/61 (39.3%)		44/117 (37.6%)
Migraine	4/56 (7.1%)		3/61 (4.9%)		7/117 (6%)
Myasthenia gravis	12/56 (21.4%)		5/61 (8.2%)		17/117 (14.5%)
Psychiatric disorders
Anxiety	4/56 (7.1%)		4/61 (6.6%)		8/117 (6.8%)
Depression	3/56 (5.4%)		8/61 (13.1%)		11/117 (9.4%)
Insomnia	7/56 (12.5%)		2/61 (3.3%)		9/117 (7.7%)
Renal and urinary disorders
Dysuria	3/56 (5.4%)		1/61 (1.6%)		4/117 (3.4%)
Reproductive system and breast disorders
Ovarian cyst	3/38 (7.9%)		0/41 (0%)		3/79 (3.8%)
Respiratory, thoracic and mediastinal disorders
Asthma	3/56 (5.4%)		2/61 (3.3%)		5/117 (4.3%)
Cough	12/56 (21.4%)		10/61 (16.4%)		22/117 (18.8%)
Oropharyngeal pain	3/56 (5.4%)		9/61 (14.8%)		12/117 (10.3%)
Productive cough	3/56 (5.4%)		1/61 (1.6%)		4/117 (3.4%)
Skin and subcutaneous tissue disorders
Alopecia	3/56 (5.4%)		2/61 (3.3%)		5/117 (4.3%)
Eczema	3/56 (5.4%)		3/61 (4.9%)		6/117 (5.1%)
Pruritus	4/56 (7.1%)		4/61 (6.6%)		8/117 (6.8%)
Rash	3/56 (5.4%)		3/61 (4.9%)		6/117 (5.1%)
Urticaria	3/56 (5.4%)		1/61 (1.6%)		4/117 (3.4%)
Vascular disorders
Hypertension	6/56 (10.7%)		0/61 (0%)		6/117 (5.1%)

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor can review results communications at least 60 days prior to public release. Within 30 days of receipt, Sponsor shall advise of any information which is Confidential Information (other than Study Data) or which may impair the availability of patent protection for Inventions. Sponsor can require removal of specifically identified Confidential Information (other than Study Data) and/or delay the communication an additional 60 days to enable Sponsor to seek patent protection for Inventions.