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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 16 November 2015
Main ID:  EUCTR2011-002068-26-DE
Date of registration: 05/10/2011
Prospective Registration: Yes
Primary sponsor: GlaxoSmithKline Research & Development Limited
Public title: A Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamics of Belimumab in Subjects with Generalized Myasthenia Gravis (MG)
Scientific title: A Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamics of Belimumab in Subjects with Generalized Myasthenia Gravis (MG).
Date of first enrolment: 24/11/2011
Target sample size: 42
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002068-26
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2  
Phase: 
Countries of recruitment
Canada Germany Italy United States
Contacts
Name: GSK Clinical Support Helpdesk   
Address:  Iron Bridge Road, Stockley Park West UB11 1BU Uxbridge, Middlesex United Kingdom
Telephone: +44(0)208990 4466
Email: GSKClinicalSupportHD@gsk.com
Affiliation:  GlaxoSmithKline
Name: GSK Clinical Support Helpdesk   
Address:  Iron Bridge Road, Stockley Park West UB11 1BU Uxbridge, Middlesex United Kingdom
Telephone: +44(0)208990 4466
Email: GSKClinicalSupportHD@gsk.com
Affiliation:  GlaxoSmithKline
Key inclusion & exclusion criteria
Inclusion criteria:
Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Subjects aged 18 years and older, with life expectancy of greater than 1 year.
2. MG of class II to IVa inclusive.
3. Acetylcholine receptor (AChR) or muscle-specific kinase (MuSK)antibody positive.
4. Stable dose (defined as no dose changes) not exceeding the maximum doses given in Section 5.6.1 of protocol, the following therapy(ies) prior to screening:
A. Cholinesterase inhibitor(pyridostigmine or equivalent) for at least 2 weeks prior to screening and no immunosuppressants;
or
B. Cholinesterase inhibitor (pyridostigmine or equivalent) for at least 2 weeks prior to screening and/or only one of the following:
i. prednisone (up to 40 mg/day or equivalent) for at least 1 month prior to screening,
ii. azathioprine for at least 6 months prior to screening,
iii. mycophenolate for at least 6 months prior to screening,
iv. cyclosporine for at least 3 months prior to screening;
v. methotrexat for at least 3 months prior to screening
or
C. Cholinesterase inhibitor (pyridostigmine or equivalent) for at least 2 weeks prior to screening and/or prednisone (up to 20 mg/day or
equivalent) for at least 1 month prior to screening and only one of the following:
i. azathioprine for at least 6 months prior to screening,
ii. mycophenolate for at least 6 months prior to screening,
iii. cyclosporine for at least 3 months prior to screening
iv. methotrexat for at least 3 months prior to screening
5. Quantitative Myasthenia Gravis (QMG) score of 8 or greater, with at least 4 points derived from signs other than ocular
6. A female subject is eligible to participate if she is:
A. Of non-childbearing potential
B. Of childbearing potential and NOT pregnant or nursing, has a negative serum
pregnancy test at screening, and agrees to one of the following:
a. Complete abstinence from penile-vaginal intercourse, when this is the
female’s preferred and usual lifestyle, for the period from consent into the study until 16 weeks after the last dose of investigational product; or,
b. Consistent and correct use of one of the following acceptable methods of
birth control for the period from consent into the study until 16 weeks
after the last dose of investigational product:
i. Oral contraceptives (either combined or progesterone only)
ii. Injectable progesterone
iii. Implants of etonogestrel or levonorgestrel
iv. Estrogenic vaginal ring
v. Percutaneous contraceptive patches
vi. Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of <1% per year
vii. Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject’s entry into the study;
this male must be the sole partner for the subject
viii. Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent(foam/gel/film/cream/suppository).
A female is considered “Non-childbearing potential” if she is status-post hysterectomy,
status-post surgical removal of both ovaries, has current, documented tubal ligation, or is
postmenopausal and >2 years without menses. Female subjects who are post-menopausal
<2 years must be confirmed menopausal by Follicle Stimulating Hormone (FSH) and
estradiol levels.
A female is considered “childbearing potential” if she has functional ovaries, ducts, and
uterus with no impairment that would cause sterility. This includes women with oligomeno

Exclusion criteria:
Subjects meeting any of the following criteria must not be enrolled in the study:
1. The subject has participated in a clinical trial and has received an investigational product within 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) prior to screening or planning to take any investigational drug for the planned duration of study participation (6
months after the last dose of study drug).
2. Presence or previous history of thymoma.
3. Thymectomy within 12 months
4. Clinically significant (in the opinion of investigator) abnormal laboratory values.
5. Pregnant females as determined by positive (serum) hCG test at screening or prior to dosing, or lactating females or planning to become pregnant within 16 weeks after last dose of investigational product.
6. History of sensitivity to any of the study medications, or components thereof or a
history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
7. May require (in the opinion of investigator) treatment with IVIg and/or plasmapheresis during the 12 weeks after the screening visit.
8. Have received IVIg and/or plasmapheresis within 4 weeks prior to screening.
9. Have received any other biopharmaceutical agent (except IVIg as described in exclusion criteria #8) in the 364 days prior to screening.
10. Have received treatment with rituximab within 12 months prior to screening or have received treatment with belimumab or any other B cell targeted therapy at any time.
11. Have received a live vaccine within 30 days of study Day 0 (baseline).
12. Have received cyclophosphamide or any other immunosuppressive agent apart from
the ones allowed by the inclusion criteria #4, within the past 6 months.
13. Have another medical condition that requires treatment with steroids or immunosuppressive agents.
14. Hospitalization due to infection or use of parenteral antibacterial, antifungal or antiviral agents within 60 days prior to screening; or history of recurrent or chronic infection, or currently active systemic infection.
15. Have a history of malignant neoplasm within the last 5 years, except for adequately
treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the
uterine cervix.
16. Have a history of a major organ transplant (eg, heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.
17. Have a historically positive test or test positive at screening for HIV-1, hepatitis B surface antigen, hepatitis B core antibody or hepatitis C antibody (Patients who are positive for hepatitis C antibody but negative for a confirmatory RNA test will be eligible to participate.)
18. Have an IgG Grade 3 or greater deficiency (= 400mg/dL).
19. Have an IgA deficiency (IgA < 10mg/dL).
20. Have a history of an anaphylactic reaction to parenteral administration of contrast
agents, human or murine proteins or monoclonal antibodies.
21. The subject has a progressive medical, neurological or psychological condition or
situation that, in the investigator’s judgment, is likely to cause the subject to be unable or unwilling to participate in study procedures, to complete all scheduled assessments, or precludes accurate assessments.
22. Is currently abusing drugs or alcohol or has history of abuse in the last 12 months.
23. Subjects who have evidence of serious suicide risk including any history of suicidal
be


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Myasthenia Gravis
MedDRA version: 17.0 Level: PT Classification code 10028417 Term: Myasthenia gravis System Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
Intervention(s)

Trade Name: BENLYSTA® (belimumab)
Product Name: Benlysta (belimumab)
Product Code: GSK1550188
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: belimumab
CAS Number: 356547-88-1
Current Sponsor code: GSK1550188
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 80-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)
Main Objective: To assess the efficacy of belimumab in subjects with MG by testing the hypothesis that belimumab will be more effective than placebo in reducing signs of MG as measured by the Quantitative Myasthenia Gravis (QMG) score.
Primary end point(s): The primary efficacy endpoint is the mean change from baseline for QMG score at Week 24.
Secondary Objective: • To further assess efficacy of belimumab in subjects with MG
• To assess safety, tolerability, and pharmacodynamics of belimumab in subjects with MG
Timepoint(s) of evaluation of this end point: Week 24
Secondary Outcome(s)
Secondary end point(s): QMG Score:
• Proportion of subjects with improvement by = 3points from baseline to Week 24 in QMG score
• Proportion of subjects with a sustained response (improve by = 3 points from baseline to Week 12 and maintain the response through Week 24) in the QMG score
• Proportion of subjects with a worsening by = 3 points in QMG score from baseline to Week 24
• Median time to QMG response which is sustained (from earliest time point at which
improvement by = 3 points from baseline is observed and maintained through Week 24)
• Mean change from baseline for QMG score at Week 28, Week 32, and Week 36.

MG Composite (MGC) Score:
• Mean change from baseline in MGC at Week 24
• Proportion of subjects with improvement by = 3points from baseline to Week 24 in the MG Composite (MGC) score
• Proportion of subjects with a sustained response (improve by = 3 points from
baseline to Week 12 and maintain the response through Week 24) in MGC score
• Proportion of subjects with a worsening by = 3 points in MGC score from baseline to Week 24
• Median time to MGC score response which is sustained (from earliest time point at which improvement by = 3 points from baseline is observed and maintained through Week 24)
• Mean change from baseline for MGC score at Week 28, Week 32, and Week 36.

Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status:
• Proportion of subjects with a MGFA post-intervention status of Minimal Manifestation (MM) or better at Week 24 and Week 36
• Proportion of subjects with MGFA post-intervention status of Pharmacologic Remission (PR) or better at Week 24 and Week 36
• Proportion of subjects with a MGFA post-intervention status of MM sustained response (MM at Week 12 and maintained the response through Week 24)
• Proportion of subjects with MGFA post-intervention status of PR sustained response
(PR at Week 12 and maintained the response through Week 24)
• Proportion of subjects with MGFA post-intervention status (Unchanged, Improved,
Worsened) at Week 24
MG Activities of Daily Living Scale (MG-ADL):
• Mean change from baseline in the MG-ADL at Week 12 and Week 24
• Mean change from baseline in the MG-ADL at Week 28, Week 32, and Week 36

Other
Pharmacokinetics:
• Individual serum concentrations of belimumab at Day 0, Week 2, Week 8, Week 20, Week 24 and Week 28.

Pharmacodynamics/biomarkers:
• Change from baseline to Week 8, Week 24, Week 28 and to Week 36 in acetylcholine receptor (AChR/MuSK) antibody titre
• Change from baseline to Week 8, Week 24, Week 28 and Week 36 in B cell and T cell subsets
Safety
• Frequency and severity of adverse events (AEs)
• Frequency of serious adverse events (SAEs)
• Percentage of subjects withdrawing due to AEs
• Percentage of subjects with drug-related AEs
• Change from baseline in vital signs.
• Frequency of vital signs of clinical concern
• Change from baseline in hematology and chemistry parameters.
• Frequency of hematology and chemistry parameters of potential clinical concern
• Percentage of subjects withdrawing from study due to MG worsening/exacerbation
• Percentage of subjects withdrawing from the study due to MG improvement and the
need to decrease dose of MG concomitant medications more than allowed per protocol.
• Percentage of subjects that decrease dose of MG concomitant medications due to MG improvement (regardless of withdrawal status).
• Incidence of positive immunogenicity demonstrating the presence of anti-belimumab
antibodies.
Timepoint(s) of evaluation of this end point: QMG:Mean change from baseline for QMG score at:
wk4, wk8, wk12, wk16, wk20, wk24, wk28, wk32, wk36.
MG Composite (MGC) Score:Mean change from baseline for MGC score at wk2, wk4, wk8, wk12, wk16, wk20, wk24, wk28, wk32, wk36.
MGFA Post-Intervention Status: wk12, wk24, wk 36
MG Activities of Daily Living Scale (MG-ADL):
wk4, wk8, wk12, wk16, wk20, wk24, wk28, wk32, wk36.
Secondary ID(s)
BEL115123
Source(s) of Monetary Support
GlaxoSmithKline Research & Development Limited
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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