A Pilot Study of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Generalized Myasthenia Gravis

NCT01555580 | Unknown Early Phase 1

• 1 other identifier: MDA 2011 MG GM-CSF
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether the drug Leukine (GM-CFS) is safe and tolerated by patients with autoimmune myasthenia gravis (MG).

Conditions

Myasthenia Gravis

Keywords

myasthenia gravis; autoimmune; GM-CSF

Outcome Measures

Primary Outcomes (4)

• Safety of GM-CSF in patients with myasthenia gravis

  The number of subjects experiencing a Class II-V adverse event within 120 days of the start of treatment that is probably or definitely related to the study medication

  150 days

• The change from baseline in the quantitative and functional (suppressive capacity) characterization of circulating regulatory T cells at 30 days post-treatment

  30 days

• The change from baseline in the quantitative and functional (suppressive capacity) characterization of circulating regulatory T cells at 60 days post-treatment

  60 days

• The change from baseline in the quantitative and functional (suppressive capacity) characterization of circulating regulatory T cells at 120 days post-treatment

  120 days

Secondary Outcomes (14)

• Change from baseline in the Quantitative Myasthenia Gravis (QMG) score at 60 days

  60 days

• Change from baseline in the Quantitative Myasthenia Gravis (QMG) score at day 120

  120 days

• Change from baseline in the Myasthenia Gravis Composite score at day 60

  60 days

• Change from baseline in the Myasthenia Gravis Composite score at day 120

  120 days

• Change from baseline in Manual Muscle Testing (MMT) score at day 60

  60 days

Study Arms (1)

GM-CSF

EXPERIMENTAL

Drug: Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) DRUG

Participants will receive one dose of GM-CSF (5 µg/kg) by subcutaneous injection for ten (10) consecutive days. The first dose of GM-CSF will be administered by the subject or caregiver under the observation and direction of the study staff during the baseline visit. The subject or caregiver will administer subsequent injections at home.

Also known as: LEUKINE® (sargramostim)

GM-CSF

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be between 18 and 80 years of age
• Established diagnosis of myasthenia based on: the presence of fatigable weakness of ocular, oropharyngeal, and/or limb muscles AND the presence of abnormal acetylcholine receptor binding antibodies ≥ 0.4 nmol/l.
• Patients of childbearing potential must agree to use a medically acceptable form of contraception defined by consistent use of oral contraceptive medications or history of tubal ligation or men who are in sexual relationship with such women during and for at least 8 weeks following completion of the study.
• Patient or designee must have the ability to self-inject investigational product
• If thymectomized, the procedure must have been performed at least one year prior to screening.
• Dose of current anticholinesterase drugs must be constant for 2 weeks prior to screening.
• If taking prednisone, dose must be stable for ≥4 weeks prior to screening.

You may not qualify if:

• exclusively ocular MG (MGFA Class I)
• severe respiratory and/ or swallowing muscle weakness (MGFA Class Vb or V)
• presence of thymoma
• Must not have received plasm exchange or IVIG within 4 weeks of screening
• Must not have received immuno-modulating agents within the 4 weeks of screening, including Azathioprine (Imuran), Cyclosporine (Sandimmune, Neoral), Mycophenolate mofetil (CellCept), GM-CSF (Filgrastim; Neupogen; pegfilgrastim, sargramostim), or any other chronic immunosuppressive agent
• History of tuberculosis or evidence of latent tuberculosis (positive PPD skin test or a chest X-ray with evidence of tuberculosis)
• vital capacity of less than 1.2 liters or on supplemental oxygen therapy.
• severe comorbidities including lung disease, stroke, congestive heart failure of any severity, myocardial infarction, EKG abnormalities, uncontrolled hypertension - (sitting systolic BP \<80 or \> 160 mm Hg or diastolic BP \> 100 mm Hg, unstable angina pectoris, hepatic or renal disease, insulin-dependent diabetes mellitus, history of cancer (other than in-situ cervical cancer or resected, cutaneous basal cell or squamous cell carcinoma), open cutaneous ulcers, known hepatitis B surface antigen (HbsAg) or hepatitis C virus (HCV) positive, or any other concurrent medical condition, which would make it unsafe for subjects to participate in the trial or interfere with the interpretation of the results.
• Laboratories values which, at the time of the screening visit or at any time during the study that in the opinion of the Investigator would preclude participation in the study including: serum creatinine \> 2.5 mg/dL, serum potassium \< 3.5 mmol/L or \> 5.5 mmol/L, serum aspartate transaminase (AST), alanine transaminase (ALT), or alkaline phosphatase (ALP)\> 3 times the upper limit of normal, platelet count \< 100,000/mm3, WBC count \< 3,000 cells/mm3, Hemoglobin, hematocrit, or red blood cell count outside 30% of the upper or lower limits of normal
• Receipt of a live vaccine within 3 months of screening
• participation in another investigational drug study within 90 days of screening.
• known hypersensitivity to GM-CSF or any of its components
• Known HIV-positive status or known history of any other immuno-suppressing disease.
• Any mycobacterial disease.
• Active severe infections within 4 weeks before screening visit, or between the screening and baseline visits.

Sponsors & Collaborators

• Muscular Dystrophy Association: lead

Study Sites (1)

University of Illinois at Chicago, Department of Neurology

Chicago, Illinois, 60612, United States

Location

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim

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)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Matthew N Meriggioli, MD

  University of Illinois at Chicago, 912 S. Wood St., Rm 855-N, M/C 796, Chicago IL 60612

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthew N Meriggioli, MD

CONTACT

312-996-4780; mmerig@uic.edu

Margaret O'Connor, RN

CONTACT

312-413-8605; moconn@uic.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 13, 2012
• First Posted: March 15, 2012
• Study Start: April 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: March 15, 2012

Record last verified: 2012-03

Locations

US (1)