Clinical trial NCT03059888: Trial of Orencia in Patients With Myasthenia Gravis
Official title: Pilot Trial of Orencia in Myasthenia Gravis Patients Inadequately Responsive to Conventional Immunotherapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Myasthenia Gravis
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2017-02-23
Enrollment: 6
Sex: ALL
Minimum age (years): 16
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This pilot research study is being done to see if the drug abatacept (Orencia ®) will be helpful in treating patients with myasthenia gravis (MG) who do not respond satisfactorily to other drugs that are used to suppress the immune system. Abatacept has been successful in treating experimental MG in laboratory animals, and this study is to determine its effectiveness in patients with MG.


Eligibility criteria: Inclusion Criteria:

* Able to comprehend and willing to sign an Informed Consent Form (ICF)
* Male or female 16 to 85 years of age
* Diagnosis of DEFINITE Myasthenia Gravis
* History of inadequate response to conventional MG treatment
* Clinical laboratory findings within the normal range or, if outside the normal range, deemed not clinically significant by the Investigator
* Female patients of childbearing potential who are not be breastfeeding, have a negative pregnancy test, have no intention to become pregnant during the course of the study, and are using contraceptive drugs or devices to prevent pregnancy during their participation in the study
* Willing to cooperate with study requirements, including visits to the study site every 2 months.

Exclusion Criteria:

* Subject's MG is responding adequately to conventional immunosuppressive treatment
* Subject has had no previous trial of other immunosuppressive agents
* Subject has a history of Chronic Obstructive Pulmonary Disease (COPD)
* Subject is impaired, incapacitated or incapable of completing study-related assessments
* Subject has the presence at screening of any severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurologic or cerebral disease, whether or not related to MG that, in the opinion of the Investigator, might place the subject at unacceptable risk for participation in the study.
* Female subject has a history of breast cancer screening that is suspicious for malignancy and in whom the possibility of malignancy cannot be reasonably excluded by additional clinical, laboratory or other diagnostic evaluations
* Subject has a history of cancer in the last 5 years, other than non-melanoma skin cell cancers cured by local resection or carcinoma in situ
* Subject currently abuses drugs or alcohol
* Subject has evidence of active or latent bacterial or viral infections, including positive infectious disease laboratory test result (Hepatitis B, Hepatitis C or HIV)
* Subject has history of herpes zoster or cytomegalovirus (CMV) infection that resolved less than 2 months prior to screening visit
* Subject has received any live vaccine within 3 months of screening
* Subject has a history of serious bacterial infection within in the last 3 months, unless treated and resolved with antibiotics; or, any chronic bacterial infection
* Subject is at risk for tuberculosis
* Subject has any of the following laboratory values: Hemoglobin \< 8.5 g/dL; White Blood Cells (WBC) \< 3000 mm3; Platelets \< 100,000 mm3; Serum creatinine \> 2x upper limit of normal (ULN); Serum Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) \> 2x ULN
* Subject is unable or unwilling to maintain weekly injection schedule
* Subject has undergone a change in immunosuppressive medications within the last three months prior to enrollment.
* Subject has neurological impairment due to a condition other than MG, including history of transient ischemic attack within the past year
* Subject has taken any investigational study drug within 28 days or five half-lives of the prior agent, whichever is greater, prior to dosing
* Subject has had previous exposure to Orencia (abatacept)
* Subject is a prisoner or is involuntarily incarcerated
* Subject is compulsorily detained for treatment of either psychiatric or physical illness
* Subject is judged to be actively suicidal or a suicide risk by the Investigator

Primary outcomes:
measure: Subjective Composite Score of Myasthenia Gravis (MG) Severity
timeFrame: 12 months
measure: Objective Composite Score of Myasthenia Gravis (MG) Severity
timeFrame: 12 months
measure: Muscle Strength (Dynamometry)
timeFrame: 12 months
Secondary outcomes:
measure: Myasthenia Gravis Composite Score (MGC)
timeFrame: 12 months
measure: Myasthenia Gravis Quality of Life-15 (MG QOL15) Score
timeFrame: 12 months
measure: Acetylcholine Receptor (AChR) or Muscle-Specific Kinase (MuSK) Antibody Concentrations
timeFrame: 12 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Daniel Drachman, MD
role: PRINCIPAL_INVESTIGATOR
References: