The Evaluation of Belimumab in Myasthenia Gravis (MG)

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT01480596
• Date of registration: 27/10/2011
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: The Evaluation of Belimumab in 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: April 2013
• Target sample size: 40
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01480596
• Study type: Interventional
• Phase: Phase 2

Countries of recruitment

Canada, Germany, Italy, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & 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 jud


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Myasthaenia Gravis

Intervention(s)

Biological: Belimumab

Other: Placebo

Primary Outcome(s)

Mean Change From Baseline for Quantitative Myasthenia Gravis (QMG) Score at Week 24 [Time Frame: Baseline and Week 24]

Secondary Outcome(s)

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 [Time Frame: Baseline and up to Week 24]

Number of Participants Worsening by >=3 Points From Baseline Through to Week 24 in the MGC Score [Time Frame: Baseline and up to Week 24]

Mean Change From Baseline in the Myasthenia Gravis Activities of Daily Living Scale (MG-ADL) at Week 12 and Week 24 [Time Frame: Baseline, Week 12 and 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 [Time Frame: Baseline and up to Week 24]

Number of Participants With a Sustained Response in the QMG Score [Time Frame: Baseline and up to Week 24]

Number of Participants Worsening by >=3 Points in QMG Score From Baseline Through to Week 24 [Time Frame: Baseline and up to Week 24]

Mean Change From Baseline for QMG Score at Week 28, Week 32 and Week 36 [Time Frame: Baseline, Week 28, Week 32 and Week 36]

Number of Participants With Improvement by >=3 Points From Baseline Through to Week 24 in the MGC Score [Time Frame: Baseline and up to Week 24]

Number of Participants With Improvement by Greater Than or Equal to (>=) 3 Points From Baseline Through to Week 24 in the QMG Score [Time Frame: Baseline and up to Week 24]

Number of Participants With MGFA-PIS of Pharmacologic Response Sustained Response (PR at Week 12 and Maintained the Response Through Week 24) [Time Frame: Week 12 through 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 [Time Frame: 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. [Time Frame: Week 24 and Week 36]

Number of Participants With a Sustained Response in the MGC Score [Time Frame: Baseline and up to Week 24]

Number of Participants With MGFA-PIS (Unchanged, Improved, Worsened) at Week 24 and Week 36 [Time Frame: Week 24 and Week 36]

Mean Change From Baseline for MGC Score at Week 28, Week 32 and Week 36 [Time Frame: Baseline, Week 28, Week 32 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) [Time Frame: Week 12 through Week 24]

Number of Participants With MGFA-PIS of Pharmacologic Remission or Better at Week 24 and Week 36 [Time Frame: Week 24 and Week 36]

Mean Change From Baseline in Myasthenia Gravis Composite (MGC) Scale Through to Week 24 [Time Frame: Baseline and up to Week 24]

Secondary ID(s)

115123

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 27/04/2016
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01480596