Myasthenia Gravis MedDRA version: 17.0 Level: PT Classification code 10028417 Term: Myasthenia gravis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
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
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion 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 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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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.;Secondary Objective: • To further assess efficacy of belimumab in subjects with MG • To assess safety, tolerability, and pharmacodynamics of belimumab in subjects with MG;Primary end point(s): The primary efficacy endpoint is the mean change from baseline for QMG score at Week 24.;Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 s | — |
Countries
Canada, Germany, Italy, United States
Contacts
Public ContactGSK Clinical Support Helpdesk
GlaxoSmithKline
Outcome results
None listed