Flag of the European Union

EU Clinical Trials Register

Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:

interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC

clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
Clinical Trials Information System (CTIS).

The EU Clinical Trials Register currently displays 43858 clinical trials with a EudraCT protocol, of which 7284 are clinical trials conducted with subjects less than 18 years old. The register also displays information on 18700 older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).

Examples: Cancer AND drug name. Pneumonia AND sponsor name.
How to search [pdf]

Advanced Search:

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

< Back to search results

Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Eculizumab in Subjects With Refractory Generalized Myasthenia Gravis (gMG)

Summary
EudraCT number	2013-003589-15
Trial protocol	SE IT GB DE ES BE NL DK GR FI HU CZ FR
Global end of trial date	01 Jun 2016

Results information
Results version number	v1(current)
This version publication date	24 Mar 2017
First version publication date	24 Mar 2017
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

ECU-MG-301

ISRCTN number

-

US NCT number

NCT01997229

WHO universal trial number (UTN)

-

Sponsor organisation name

Alexion Pharmaceuticals

Sponsor organisation address

100 College Street, New Haven, United States, 06510

Public contact

Alexion Europe SAS, European Clinical Trial Information, +33 1 47 10 06 06, clinicaltrials.eu@alexion.com

Scientific contact

Alexion Europe SAS, European Clinical Trial Information, +33 1 47 10 06 06, clinicaltrials.eu@alexion.com

Is trial part of an agreed paediatric investigation plan (PIP)

No

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Analysis stage

Final

Date of interim/final analysis

01 Jun 2016

Is this the analysis of the primary completion data?

Yes

Primary completion date

19 Feb 2016

Global end of trial reached?

Yes

Global end of trial date

01 Jun 2016

Was the trial ended prematurely?

No

Main objective of the trial

The primary objective of this trial was to assess the efficacy of eculizumab as compared with placebo in the treatment of refractory gMG based on the improvement in the Myasthenia Gravis-specific Activities of Daily Living profile (MG-ADL).

Protection of trial subjects

Not Applicable

Background therapy

Standard of care MG therapy, including cholinesterase inhibitors and immunosuppressive therapies, could be maintained at a stable dose during the study.

Evidence for comparator

Matched placebo

Actual start date of recruitment

30 Apr 2014

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

No

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 44

Country: Number of subjects enrolled

Japan: 11

Country: Number of subjects enrolled

Spain: 9

Country: Number of subjects enrolled

Belgium: 7

Country: Number of subjects enrolled

Italy: 7

Country: Number of subjects enrolled

Argentina: 6

Country: Number of subjects enrolled

Brazil: 6

Country: Number of subjects enrolled

Czech Republic: 5

Country: Number of subjects enrolled

Denmark: 6

Country: Number of subjects enrolled

Korea, Republic of: 5

Country: Number of subjects enrolled

Turkey: 5

Country: Number of subjects enrolled

United Kingdom: 5

Country: Number of subjects enrolled

Hungary: 4

Country: Number of subjects enrolled

Canada: 2

Country: Number of subjects enrolled

Finland: 1

Country: Number of subjects enrolled

Netherlands: 1

Country: Number of subjects enrolled

Sweden: 1

Worldwide total number of subjects

125

EEA total number of subjects

46

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

0

Adults (18-64 years)

99

From 65 to 84 years

26

85 years and over

0

Subject disposition

Top of page

Recruitment details

Subjects with refractory generalized myasthenia gravis were screened to confirm study eligibility.

Screening details

Prior to randomization, subjects continued on standard of care treatment and were vaccinated against Neisseria meningitidis, if not already vaccinated within the active coverage specified by the vaccine manufacturer or according to current medical/country guidelines. The washout period for IVIg and PE was 4 weeks prior to randomization.

Period 1 title

Treatment Period (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo

Arm description

-

Arm type

Placebo

Investigational medicinal product name

Matched Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravascular use

Dosage and administration details

Induction phase: 3 vials of study drug (placebo) weekly for 4 doses (every 7 days ± 2 days) followed by 4 vials of study drug (placebo) 1 week later for the fifth dose (Week 4). Maintenance phase: 4 vials of study drug (placebo) every 2 weeks (14 days ± 2 days) from the fifth dose onwards (Week 6 through Week 26).

Eculizumab

Arm description

-

Arm type

Experimental

Investigational medicinal product name

Eculizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravascular use

Dosage and administration details

Induction phase: 3 vials of study drug (equivalent to 900 mg of eculizumab) weekly for 4 doses (every 7 days ± 2 days) followed by 4 vials of study drug (equivalent to 1200 mg of eculizumab) 1 week later for the fifth dose (Week 4). Maintenance phase: 4 vials of study drug (equivalent to 1200 mg of eculizumab) every 2 weeks (14 days ± 2 days) from the fifth dose onwards (Week 6 through Week 26).

Number of subjects in period 1	Placebo	Eculizumab
Started	63	62
Completed	61	57
Not completed	2	5
Consent withdrawn by subject	2	1
Adverse event, non-fatal	-	4

Baseline characteristics

Top of page

Reporting group title

Placebo

Reporting group description

-

Reporting group title

Eculizumab

Reporting group description

-

Reporting group values	Placebo	Eculizumab	Total
Number of subjects	63	62	125
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	46.9 ( 17.98 )	47.5 ( 15.66 )	-
Gender categorical
Units: Subjects
Female	41	41	82
Male	22	21	43

End points

Top of page

Reporting group title

Placebo

Reporting group description

-

Reporting group title

Eculizumab

Reporting group description

-

Primary: Myasthenia Gravis Activities of Daily Living profile (MG-ADL): Change from Baseline in MG-ADL Total Score at Week 26 by Worst-Rank Analysis of Covariance (ANCOVA)

Top of page

End point title

Myasthenia Gravis Activities of Daily Living profile (MG-ADL): Change from Baseline in MG-ADL Total Score at Week 26 by Worst-Rank Analysis of Covariance (ANCOVA)

End point description

End point type

Primary

End point timeframe

End of study (Week 26)

End point values	Placebo	Eculizumab
Number of subjects analysed	63	62
Units: Worst-Rank score
least squares mean (standard error)	68.3 ( 4.49 )	56.6 ( 4.53 )

MG-ADL Worst-Rank ANCOVA

Comparison groups

Placebo v Eculizumab

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0698

Method

ANCOVA

Parameter type

Mean difference (net)

Point estimate

-11.7

Confidence interval

level

95%

sides

2-sided

lower limit

-24.33

upper limit

0.96

Adverse events

Top of page

Timeframe for reporting adverse events

26 weeks (Study Period) + 8 weeks (Follow-up Period for subjects who discontinued the Study Period or completed the Study Period but did not enroll in the ECU-MG-302 extension trial).

Adverse event reporting additional description

Treatment-emergent adverse events were collected at every visit and during follow-up.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.1

Reporting group title

Placebo

Reporting group description

-

Reporting group title

Eculizumab

Reporting group description

-

Serious adverse events	Placebo	Eculizumab
Total subjects affected by serious adverse events
subjects affected / exposed	18 / 63 (28.57%)	9 / 62 (14.52%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Investigations
Lymphocyte count decreased
subjects affected / exposed	1 / 63 (1.59%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone
subjects affected / exposed	0 / 63 (0.00%)	1 / 62 (1.61%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	0 / 63 (0.00%)	1 / 62 (1.61%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Intentional overdose
subjects affected / exposed	1 / 63 (1.59%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	1 / 63 (1.59%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Myasthenia gravis
subjects affected / exposed	8 / 63 (12.70%)	5 / 62 (8.06%)
occurrences causally related to treatment / all	0 / 17	1 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Myasthenia gravis crisis
subjects affected / exposed	0 / 63 (0.00%)	1 / 62 (1.61%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Lymphopenia
subjects affected / exposed	0 / 63 (0.00%)	1 / 62 (1.61%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
General physical health deterioration
subjects affected / exposed	1 / 63 (1.59%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 63 (0.00%)	2 / 62 (3.23%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Gastritis
subjects affected / exposed	1 / 63 (1.59%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal perforation
subjects affected / exposed	0 / 63 (0.00%)	1 / 62 (1.61%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	1 / 63 (1.59%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Apnoea
subjects affected / exposed	1 / 63 (1.59%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	1 / 63 (1.59%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Bacteraemia
subjects affected / exposed	0 / 63 (0.00%)	1 / 62 (1.61%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 63 (0.00%)	1 / 62 (1.61%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Endocarditis
subjects affected / exposed	0 / 63 (0.00%)	1 / 62 (1.61%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 63 (1.59%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed	1 / 63 (1.59%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	2 / 63 (3.17%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection bacterial
subjects affected / exposed	1 / 63 (1.59%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Varicella
subjects affected / exposed	1 / 63 (1.59%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Hyperglycaemia
subjects affected / exposed	1 / 63 (1.59%)	0 / 62 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	Eculizumab
Total subjects affected by non serious adverse events
subjects affected / exposed	53 / 63 (84.13%)	52 / 62 (83.87%)
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	2 / 63 (3.17%)	5 / 62 (8.06%)
occurrences all number	2	15
Nervous system disorders
Dizziness
subjects affected / exposed	5 / 63 (7.94%)	5 / 62 (8.06%)
occurrences all number	10	5
Headache
subjects affected / exposed	12 / 63 (19.05%)	10 / 62 (16.13%)
occurrences all number	28	25
Myasthenia gravis
subjects affected / exposed	5 / 63 (7.94%)	1 / 62 (1.61%)
occurrences all number	6	1
Paraesthesia
subjects affected / exposed	4 / 63 (6.35%)	3 / 62 (4.84%)
occurrences all number	8	3
General disorders and administration site conditions
Chills
subjects affected / exposed	4 / 63 (6.35%)	1 / 62 (1.61%)
occurrences all number	9	2
Oedema peripheral
subjects affected / exposed	2 / 63 (3.17%)	4 / 62 (6.45%)
occurrences all number	2	7
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	8 / 63 (12.70%)	8 / 62 (12.90%)
occurrences all number	8	10
Nausea
subjects affected / exposed	9 / 63 (14.29%)	8 / 62 (12.90%)
occurrences all number	26	11
Vomiting
subjects affected / exposed	5 / 63 (7.94%)	3 / 62 (4.84%)
occurrences all number	6	5
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	4 / 63 (6.35%)	1 / 62 (1.61%)
occurrences all number	9	1
Psychiatric disorders
Insomnia
subjects affected / exposed	5 / 63 (7.94%)	2 / 62 (3.23%)
occurrences all number	5	2
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	6 / 63 (9.52%)	5 / 62 (8.06%)
occurrences all number	6	6
Myalgia
subjects affected / exposed	2 / 63 (3.17%)	5 / 62 (8.06%)
occurrences all number	2	6
Pain in extremity
subjects affected / exposed	2 / 63 (3.17%)	4 / 62 (6.45%)
occurrences all number	2	4
Infections and infestations
Nasopharyngitis
subjects affected / exposed	10 / 63 (15.87%)	9 / 62 (14.52%)
occurrences all number	13	13
Oral herpes
subjects affected / exposed	0 / 63 (0.00%)	5 / 62 (8.06%)
occurrences all number	0	5
Upper respiratory tract infection
subjects affected / exposed	10 / 63 (15.87%)	10 / 62 (16.13%)
occurrences all number	12	14
Urinary tract infection
subjects affected / exposed	5 / 63 (7.94%)	4 / 62 (6.45%)
occurrences all number	7	5

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

13 Jun 2014

A global amendment included the following significant changes: (1) extended the follow-up period to 8 weeks based on pharmacokinetic characteristics and to align the protocol with other ongoing eculizumab studies that also have an 8-week follow-up period; (2) modified the washout period for intravenous immunoglobulin and plasma exchange from 4 weeks prior to screening to 4 weeks prior to randomization; (3) modified the inclusion criteria to require that patients have an MG-ADL total score of ≥6 at screening and randomization.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

For support, Contact us.

The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

European Medicines Agency © 1995-Wed Apr 24 11:35:40 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands