Myasthaenia Gravis Clinical Trial
Official 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)
Study BEL115123 is a randomized, placebo-controlled, double-blind, multinational study of belimumab (10 mg/kg) to investigate the efficacy and safety of belimumab in subjects with MG. The study will enroll male and female outpatients (> or equal to 18 years of age) with a diagnosis of MG who are 1) acetylcholine receptor (AChR) antibody positive or muscle specific kinase (MuSK) antibody positive, 2) on current standard of care therapy, and 3) continue to exhibit signs of MG. The study will include 3 phases: a 4 week screening period, a 24 week treatment period, and a 12 week follow-up period. IP will be administered intravenously on Days 0, 14, 28 and then every 28 days through and including Week 20. At Week 24, primary outcomes will be obtained. Follow up evaluations will be conducted at Weeks 28, 32 and 36 for all subjects. The primary objective of this study is to assess the efficacy of belimumab as evaluated by the change in the quantitative myasthenia gravis (QMG) score.
| Status | Completed |
| Enrollment | 40 |
| Est. completion date | October 2015 |
| Est. primary completion date | August 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - 18 years and older, with life expectancy of greater than 1 year. - MG of class II to IVa inclusive. - Acetylcholine receptor (AChR) or muscle specific kinase (MuSK) antibody positive. - Stable dose (defined as no dose changes) not exceeding the maximum doses given in Section 5.6.1 of the following therapy(ies) prior to screening: Cholinesterase inhibitor(pyridostigmine or equivalent) for at least 2 weeks prior to screening and no immunosuppressants; Cholinesterase inhibitor (pyridostigmine or equivalent) for at least 2 weeks prior to screening and/or only one of the following: prednisone (up to 40 mg/day or equivalent) for at least 1 month prior to screening; azathioprine for at least 6 months prior to screening; mycophenolate for at least 6 months prior to screening, or cyclosporine for at least 3 months prior to screening; or 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: azathioprine for at least 6 months prior to screening, mycophenolate for at least 6 months prior to screening, or cyclosporine for at least 3 months prior to screening - Quantitative Myasthenia Gravis (QMG) score of 8 or greater, with at least 4 points derived from signs other than ocular - A female subject is eligible to participate if she is: Of non-childbearing potential; Of childbearing potential and NOT pregnant or nursing, has a negative serum pregnancy test at screening, and agrees to one of the following: 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 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: Oral contraceptives (either combined or progesterone only), Injectable progesterone, Implants of etonogestrel or levonorgestrel, Estrogenic vaginal ring, Percutaneous contraceptive patches, Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year, 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, Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository). - Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. - Single QTc less than 450 msec; or QTc less than 480 msec in subjects with Bundle Branch Block. - AST and ALT less than 2xULN; alkaline phosphatase and bilirubin less or = to 1.5xULN (isolated bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%). Exclusion Criteria: - 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). - Presence or previous history of thymoma. - Thymectomy within 12 months - Clinically significant (in the opinion of investigator) abnormal laboratory values. - 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. - 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. - May require (in the opinion of investigator) treatment with IVIg and/or plasmapheresis during the 24 week treatment period. - Have received IVIg and/or plasmapheresis within 90 days prior to screening. - Have received any other biopharmaceutical agent (except IVIg as described in exclusion criteria #8) in the 364 days prior to screening. - Have received treatment with any B cell targeted therapy (e.g., rituximab, belimumab), at any time. - Have received a live vaccine within 30 days of study Day 0 (baseline). - Have received cyclophosphamide or any other immunosuppressive agent apart from the ones allowed by the inclusion criteria #4, within the past 6 months. - Have another medical condition that requires treatment with steroids or immunosuppressive agents. - 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. - 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. - Have a history of a major organ transplant (eg, heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant. - Have a historically positive test or test positive at screening for HIV-1, hepatitis B surface antigen or hepatitis C antibody. - Have an IgG Grade 3 or greater deficiency (less than or = to 400mg/dL). - Have an IgA deficiency (IgA less than 10mg/dL). - Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies. - 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. - Is currently abusing drugs or alcohol or has history of abuse in the last 12 months. - Subjects who have evidence of serious suicide risk including any history of suicidal behavior in the last 6 months and/or any suicidal ideation of type 4 or 5 on the C-SSRS in the last 2 months or who in the investigator's judgment, pose a significant suicide risk. |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Canada | GSK Investigational Site | Edmonton | Alberta |
| Canada | GSK Investigational Site | London | Ontario |
| Canada | GSK Investigational Site | Toronto | Ontario |
| Canada | GSK Investigational Site | Vancouver | British Columbia |
| Germany | GSK Investigational Site | Berlin | |
| Germany | GSK Investigational Site | Koeln | Nordrhein-Westfalen |
| Germany | GSK Investigational Site | Leipzig | Sachsen |
| Germany | GSK Investigational Site | Tuebingen | Baden-Wuerttemberg |
| Italy | GSK Investigational Site | Milano | Lombardia |
| Italy | GSK Investigational Site | Roma | Lazio |
| United States | GSK Investigational Site | Burlington | Vermont |
| United States | GSK Investigational Site | Chapel Hill | North Carolina |
| United States | GSK Investigational Site | Charleston | South Carolina |
| United States | GSK Investigational Site | Charlottesville | Virginia |
| United States | GSK Investigational Site | Colorado Springs | Colorado |
| United States | GSK Investigational Site | Columbus | Ohio |
| United States | GSK Investigational Site | Hershey | Pennsylvania |
| United States | GSK Investigational Site | Houston | Texas |
| United States | GSK Investigational Site | Kansas City | Kansas |
| United States | GSK Investigational Site | Los Angeles | California |
| United States | GSK Investigational Site | Miami | Florida |
| United States | GSK Investigational Site | Orange | California |
| United States | GSK Investigational Site | Phoenix | Arizona |
| United States | GSK Investigational Site | Tampa | Florida |
| United States | GSK Investigational Site | Washington | District of Columbia |
| Lead Sponsor | Collaborator |
|---|---|
| GlaxoSmithKline |
United States, Canada, Germany, Italy,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change in Quantitative Myasthenia Gravis (QMG) score for Disease Severity | Mean change in QMG total score (0 to 39) | Baseline to Week 24 | No |
| Secondary | Improvement in Quantitative Myasthenia Gravis (QMG) score for Disease Severity | Proportion of subjects with improvement by > or = to 3 points; QMG total score 0 to 39 | Baseline to Week 24 | No |
| Secondary | Sustained Improvement in Quantitative Myasthenia Gravis (QMG) Score for Disease Severity | Proportion of subjects with a sustained improvement; QMG total score 0 to 39 | Week 24 | No |
| Secondary | Worsening in Quantitative Myasthenia Gravis (QMG) score for Disease Severity | Proportion of subjects with a worsening by > or = to 3 points; QMG total score 0-39 | Baseline to Week 24 | No |
| Secondary | Time to Response based on the Quantitative Myasthenia Gravis (QMG) score for Disease Severity | Median time to QMG response which is sustained; QMG total score 0-39 | Assessed from baseline up to 24 weeks | No |
| Secondary | Change in Quantitative Myasthenia Gravis (QMG) score for Disease Severity 8 weeks after end of study treatment | Mean change in total QMG score 0-39 | Baseline to Week 28 | No |
| Secondary | Change in Quantitative Myasthenia Gravis (QMG) score for Disease Severity 12 weeks after end of study treatment | Mean change in total QMG score 0-39 | Baseline to Week 32 | No |
| Secondary | Change in Quantitative Myasthenia Gravis (QMG) score for Disease Severity 16 weeks after end of study treatment | Mean change in total QMG score 0-39 | Baseline to Week 36 | No |
| Secondary | Improvement in the Myasthenia Gravis Composite (MGC) Score for Disease Severity | Proportion of subjects with improvement by > or = 3 points, MGC total score 0-50 | Baseline to Week 24 | No |
| Secondary | Sustained Improvement in the Myasthenia Gravis Composite (MGC) Score for Disease Severity | Proportion of subjects with sustained improvement; MGC total score 0-50 | Week 24 | No |
| Secondary | Worsening in the Myasthenia Gravis Composite (MGC) Score for Disease Severity | Proportion of subjects with worsening by > or = to 3 points, MGC total score 0-50 | Baseline to Week 24 | No |
| Secondary | Time to Response based on the Myasthenia Gravis Composite (MGC) score for Disease Severity | Median time to response which is sustained; MGC total score 0-50 | Assessed from baseline up to 24 weeks | No |
| Secondary | Change in Myasthenia Gravis (MGC) Score for Disease Severity 4 weeks after end of study treatment | Mean Change in MGC total score 0-50 | Baseline to Week 28 | No |
| Secondary | Change in Myasthenia Gravis (MGC) Score for Disease Severity 8 weeks after end of study treatment | Mean Change in MGC total score 0-50 | Baseline to Week 32 | No |
| Secondary | Change in Myasthenia Gravis (MGC) Score for Disease Severity 12 weeks after end of study treatment | Mean Change in MGC total score 0-50 | Baseline to Week 36 | No |
| Secondary | Subjects with minimal myasthenia gravis symptoms based on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS) at the End of Treatment | Proportion of subjects with status of minimal manifestation or better | Week 24 | No |
| Secondary | Subjects with minimal myasthenia gravis symptoms based on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS) 4 weeks after end of study treatment | Proportion of subjects with status of minimal manifestation or better | Week 28 | No |
| Secondary | Subjects with minimal myasthenia gravis symptoms based on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS) 8 weeks after end of study treatment | Proportion of subjects with status of minimal manifestation or better | Week 32 | No |
| Secondary | Subjects with minimal myasthenia gravis symptoms based on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS) 12 weeks after end of study treatment | Proportion of subjects with status of minimal manifestation or better | Week 36 | No |
| Secondary | Subjects in pharmacologic remission based on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS) at the End of Treatment | Proportion of subjects with status of pharmacologic remission or better | Week 24 | No |
| Secondary | Subjects in pharmacologic remission based on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS) 8 weeks after end of study treatment | Proportion of subjects with status of pharmacologic remission or better | Week 28 | No |
| Secondary | Subjects in pharmacologic remission based on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS) 12 weeks after end of study treatment | Proportion of subjects with status of pharmacologic remission or better | Week 32 | No |
| Secondary | Subjects in pharmacologic remission based on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS) 16 weeks after end of study treatment | Proportion of subjects with status of pharmacologic remission or better | Week 36 | No |
| Secondary | Subjects with sustained minimal symptoms based on the Myasthenia Gravis Foundation of America (MGFA) Post-Interventions Status (PIS) at the end of treatment | Proportion of subjects with sustained minimal manifestation | Week 24 | No |
| Secondary | Subjects with sustained pharmacologic remission based on the Myasthenia Gravis Foundation of America (MGFA) Post-Interventions Status (PIS) at the end of treatment | Proportion of subjects with sustained pharmacologic remission | Week 24 | No |
| Secondary | Change in Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale at Week 12 | Mean Change in MG-ADL total score of 0-24 | Baseline to Week 12 | No |
| Secondary | Change in Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale at Week 24 | Mean Change in MG-ADL total score of 0-24 | Baseline to Week 24 | No |
| Secondary | Change in Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale 8 weeks after end of study treament | Mean Change in MG-ADL total score of 0-24 | Baseline to Week 28 | No |
| Secondary | Change in Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale 12 weeks after end of study treatment | Mean Change in MG-ADL total score of 0-24 | Baseline to Week 32 | No |
| Secondary | Change in Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale 16 weeks after end of study treament | Mean Change in MG-ADL total score of 0-24 | Baseline to Week 36 | No |
| Secondary | Subjects with unchanged myasthenia gravis disease status at the end of the study based on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS) | Proportion of subject unchanged | Week 24 | No |
| Secondary | Subjects with improved myasthenia gravis disease status at the end of the study based on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS) | Proportion of subjects improved | Week 24 | No |
| Secondary | Subjects with worsened myasthenia gravis disease status at the end of the study based on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS) | Proportion of subjects worsened | Week 24 | No |