Last updated: 07/17/2024 15:42:25
The Evaluation of Belimumab in Myasthenia Gravis (MG)
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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)
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Mean change from Baseline for quantitative myasthenia gravis (QMG) score at Week 24
Timeframe: Baseline and Week 24
Secondary outcomes:
Number of participants with improvement by greater than or equal to (>=) 3 points from Baseline through to Week 24 in the QMG score
Timeframe: Baseline and up to Week 24
Number of participants worsening by >=3 points in QMG score from Baseline through to Week 24
Timeframe: Baseline and up to Week 24
Number of participants with a sustained response in the QMG score
Timeframe: Baseline and up 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
Timeframe: Baseline and up to Week 24
Mean change from Baseline for QMG score at Week 28, Week 32 and Week 36
Timeframe: Baseline, Week 28, Week 32 and Week 36
Mean change from Baseline in Myasthenia Gravis Composite (MGC) scale through to Week 24
Timeframe: Baseline and up to Week 24
Number of participants with improvement by >=3 points from Baseline through to Week 24 in the MGC score
Timeframe: Baseline and up to Week 24
Number of participants worsening by >=3 points from Baseline through to Week 24 in the MGC score
Timeframe: Baseline and up to Week 24
Number of participants with a sustained response in the MGC score
Timeframe: Baseline and up to Week 24
Median time to MGC response which is sustained from earliest time point at which improvement by >=3 points from Baseline is observed and maintained through Week 24
Timeframe: Baseline and up to Week 24
Mean change from Baseline for MGC score at Week 28, Week 32 and Week 36
Timeframe: Baseline, Week 28, Week 32 and Week 36
Number of participants with a Myasthenia Foundation of America-post intervention status (MGFA-PIS) of minimal manifestation or better at Week 24 and Week 36.
Timeframe: Week 24 and Week 36
Number of participants with MGFA-PIS of pharmacologic remission or better at Week 24 and Week 36
Timeframe: Week 24 and Week 36
Number of participants with MGFA-PIS of minimal manifestation sustained response (MM at Week 12 and maintained the response through Week 24)
Timeframe: Week 12 through Week 24
Number of participants with MGFA-PIS of pharmacologic response sustained response (PR at week 12 and maintained the response through Week 24)
Timeframe: Week 12 through Week 24
Number of participants with MGFA-PIS (Unchanged, Improved, Worsened) at Week 24 and Week 36
Timeframe: Week 24 and Week 36
Mean change from Baseline in the Myasthenia Gravis Activities of Daily Living Scale (MG-ADL) at Week 12 and Week 24
Timeframe: Baseline, Week 12 and Week 24
Mean change from Baseline in the Myasthenia Gravis Activities of Daily Living Scale (MG-ADL) at Week 28, Week 32 and Week 36
Timeframe: Baseline, Week 28, Week 32 and Week 36
Interventions:
Biological/vaccine: Belimumab
Other: Placebo
Enrollment:
40
Observational study model:
Not applicable
Primary completion date:
2015-03-08
Time perspective:
Not applicable
Clinical publications:
Karen Hewett, Donald Sanders, Richard Grove, Christine Broderick, Todd Rudo, Ashlyn Bassiri, Marina Zvartau-Hind, Vera Bril. Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis. Neurology. 2017;90(16):e1425-e1434.
DOI: 10.1212/WNL.0000000000005323
PMID: 29661905
Medical condition
Myasthaenia Gravis
Product
belimumab
Collaborators
Not applicable
Study date(s)
April 2013 to October 2015
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- 18 years and older, with life expectancy of greater than 1 year.
- MG of class II to IVa inclusive.
- 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.
Inclusion and exclusion criteria
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.
Trial location(s)
Location
GSK Investigational Site
Chapel Hill, North Carolina, United States
Status
Study Complete
Location
GSK Investigational Site
Colorado Springs, Colorado, United States, 80907
Status
Study Complete
Location
GSK Investigational Site
Hershey, Pennsylvania, United States, 17033-0859
Status
Study Complete
Location
GSK Investigational Site
Kansas City, Kansas, United States, 66160
Status
Study Complete
Location
GSK Investigational Site
Los Angeles, California, United States, 90033
Status
Study Complete
Location
GSK Investigational Site
Orange, California, United States, 92868
Status
Study Complete
Location
GSK Investigational Site
Tuebingen, Baden-Wuerttemberg, Germany, 72076
Status
Study Complete
Location
GSK Investigational Site
Washington, District of Columbia, United States, 20037
Status
Study Complete
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2015-03-08
Actual study completion date
2015-27-10
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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