Trial of Orencia in Patients With Myasthenia Gravis

NCT03059888 | Terminated Early Phase 1 DMC FDA Drug

• 1 other identifier: IRB00100059
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Myasthenia Gravis

Outcome Measures

Primary Outcomes (3)

• Subjective Composite Score of Myasthenia Gravis (MG) Severity

  The "Subjective Score of MG Severity" is a composite score of subjective measurements of MG severity as designed by Dr. Daniel Drachman. The investigator will rate each subjective measure on a scale of 0 (no impairment) to 3 (severe impairment). The composite score of these measurements determined at baseline and at two-month increments through 12 months. The domains that make up the subjective score are: Diplopia, Ptosis, Arm strength, Leg strength, Speech, Voice, Chewing, Swallowing, Respiration, and General Health Status. The change in the composite subjective score at 12 months as compared to baseline is one of the primary outcomes. Patients that show an improvement in MG symptoms should have a lower score at 12 months as compared to baseline.

  12 months

• Objective Composite Score of Myasthenia Gravis (MG) Severity

  The "Objective Score of MG Severity" is a composite score of subjective measurements of MG severity as designed by Dr. Daniel Drachman. The investigator will score each objective measure on a scale of 0 (no impairment) to 3 (severe impairment). The composite score of these measurements determined at baseline and at two-month increments through 12 months. The domains that make up the objective score are: Diplopia, Ptosis, Arm abduction, Gait, Orbicularis Oculi, Orbicularis Oris, Tongue, Slurp Test. The change in the composite objective score at 12 months as compared to baseline is one of the primary outcomes. Patients that show an improvement in MG symptoms should have a lower score at 12 months as compared to baseline.

  12 months

• Muscle Strength (Dynamometry)

  Muscle strength in 11 muscle groups will be measured by hand-held dynamometry at baseline and at two-month increments through 12 months. The change in muscle strength (in pounds) at 12 months as compared to baseline is one of the primary outcomes. Patients that show an improvement in MG symptoms should show increased muscle strength at 12 months as compared to baseline.

  12 months

Secondary Outcomes (3)

• Myasthenia Gravis Composite Score (MGC)

  12 months

• Myasthenia Gravis Quality of Life-15 (MG QOL15) Score

  12 months

• Acetylcholine Receptor (AChR) or Muscle-Specific Kinase (MuSK) Antibody Concentrations

  12 months

Study Arms (1)

Abatacept

EXPERIMENTAL

125mg abatacept in 1ml solution administered once per week by subcutaneous injection

Drug: Abatacept Injection

Interventions

Abatacept Injection DRUG

Subcutaneous administration of abatacept

Also known as: Orencia

Abatacept

Eligibility Criteria

• Age: 16 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Officials

• Daniel Drachman, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2017
• First Posted: February 23, 2017
• Study Start: April 12, 2017
• Primary Completion: July 15, 2019
• Study Completion: July 15, 2019
• Last Updated: November 22, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)