Clinical trial NCT01480596: The Evaluation of Belimumab in Myasthenia Gravis (MG)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myasthaenia Gravis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-11-29
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Mean Change From Baseline for Quantitative Myasthenia Gravis (QMG) Score at Week 24
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: 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
measure: Number of Participants Worsening by >=3 Points in QMG Score From Baseline Through to Week 24
timeFrame: Baseline and up to Week 24
measure: Number of Participants With a Sustained Response in the QMG Score
timeFrame: Baseline and up to Week 24
measure: 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
measure: Mean Change From Baseline for QMG Score at Week 28, Week 32 and Week 36
timeFrame: Baseline, Week 28, Week 32 and Week 36
measure: Mean Change From Baseline in Myasthenia Gravis Composite (MGC) Scale Through to Week 24
timeFrame: Baseline and up to Week 24
measure: 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
measure: Number of Participants Worsening by >=3 Points From Baseline Through to Week 24 in the MGC Score
timeFrame: Baseline and up to Week 24
measure: Number of Participants With a Sustained Response in the MGC Score
timeFrame: Baseline and up to Week 24
measure: 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
measure: Mean Change From Baseline for MGC Score at Week 28, Week 32 and Week 36
timeFrame: Baseline, Week 28, Week 32 and Week 36
measure: 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
measure: Number of Participants With MGFA-PIS of Pharmacologic Remission or Better at Week 24 and Week 36
timeFrame: Week 24 and Week 36
measure: 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
measure: 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
measure: Number of Participants With MGFA-PIS (Unchanged, Improved, Worsened) at Week 24 and Week 36
timeFrame: Week 24 and Week 36
measure: 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
measure: 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
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Orange
country: United States
facility: GSK Investigational Site
state: California
city: Colorado Springs
country: United States
facility: GSK Investigational Site
state: Colorado
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Kansas
city: Chapel Hill
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Hershey
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Burlington
country: United States
facility: GSK Investigational Site
state: Vermont
city: Charlottesville
country: United States
facility: GSK Investigational Site
state: Virginia
city: Edmonton
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: London
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Tuebingen
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Koeln
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Hewett K, Sanders DB, Grove RA, Broderick CL, Rudo TJ, Bassiri A, Zvartau-Hind M, Bril V; BEL115123 Study Group. Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis. Neurology. 2018 Apr 17;90(16):e1425-e1434. doi: 10.1212/WNL.0000000000005323. Epub 2018 Mar 21.