Efficacy of Prednisone In the Treatment of Ocular Myasthenia

NCT00995722 | Terminated Phase 3 Results DMC

• 1 other identifier: FD-R-03710-01
• Study Type: interventional
• Target: 11
• Locations: 2 countries
• Sites: 10

Brief Summary

The purpose of this study is to evaluate the efficacy and tolerability of prednisone in patients diagnosed with ocular myasthenia. Funding Source - FDA OOPD

Conditions

Ocular Myasthenia Gravis

Keywords

Ocular myasthenia gravis; Prednisone; Steroids

Outcome Measures

Primary Outcomes (1)

• Treatment Failure

  Failure to achive sustatined minimal manifestation status by week 16

  4 months

Secondary Outcomes (4)

• Change in Ocular Quantitative Myasthenia Score From Baseline to Week 16

  4 months

• Change in Quality of Life as Measured by the NEI-VFQ-25 Measures

  4 months

• Change in Quality of Life as Measured by the MG-QOL-15 Score

  4 Months

• Change in Quality of Life as Measured by the 10-Item Neuro-ophthalmological Supplement to the NEI-VFQ-25

  4 months

Study Arms (2)

Prednisone + Pyridostigmine

EXPERIMENTAL

Corticosteroid

Drug: Prednisone

Placebo + Pyridostigmine

PLACEBO COMPARATOR

Matched, inactive substance

Drug: Placebo

Interventions

Prednisone DRUG

Prednisone will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain 10mg of prednisone.

Also known as: Steroid

Prednisone + Pyridostigmine

Placebo DRUG

Placebo dosages will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain matching placebo.

Also known as: Sugar pill

Placebo + Pyridostigmine

Eligibility Criteria

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

You may qualify if:

• Weakness confined to the extra-ocular muscles, eyelid levator and eye closure with an ocular-QMG1 score ≥ 1
• At least one of the following combinations of abnormal diagnostic testing: a) Elevated acetylcholine receptor antibody titers, (b) Abnormal repetitive nerve stimulation (\> 10% decrement following slow repetitive nerve stimulation) of any nerve-muscle pair, (c) Abnormal jitter on single fiber or concentric needle electromyography in any muscle, (d) Positive ice test and brain MRI that demonstrates no central nervous system pathology that mimics ocular myasthenia, or (e) Positive Tensilon test and brain MRI that demonstrate no central nervous system pathology that mimics ocular myasthenia
• Either no prior treatment with pyridostigmine, or participant has persistent ocular symptoms that are functionally limiting or troublesome despite treatment with pyridostigmine.
• Age 18 years or older, male or female
• Capable of providing informed consent and complying with study procedures
• Identifiable primary care physician to assist with management of medical complications that may arise as a consequence of steroid therapy
• Willing to be randomized to a trial of prednisone or placebo if symptoms respond inadequately to pyridostigmine.

You may not qualify if:

• Disease duration (time since symptom onset) \> 5 years
• Treatment with prednisone or other corticosteroids within 90 days of randomization
• Treatment with azathioprine, cyclosporine, mycophenolate mofetil or other immune suppressive medication since onset of MG unless dosages of these medications and/or duration of therapy with these medications are clinically insignificant in the judgment of the PI
• Intravenous immunoglobulin or plasma exchange within 90 days of randomization
• Prior thymectomy or history of thymoma
• Contraindication to steroids (poorly controlled diabetes, glaucoma or hypertension, history of prior steroid intolerance, obesity \[BMI \> 39.9kg/m2\] or a history of osteoporotic fracture)
• Pregnant or lactating
• Renal failure, active thyroid or hepatocellular disease, chronic infection, poorly controlled cardiac disease, unstable psychiatric illness, untreated major depression or any other illness that would, in the opinion of the treating neurologist, make it unsafe for the patient to participate in the trial
• Receipt of another investigational drug within 30 days of Screening

Sponsors & Collaborators

• Michael Benatar: lead
• University of Miami: collaborator
• University of Rochester: collaborator

Study Sites (10)

Yale University

New Haven, Connecticut, 06510, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University at Buffalo, Buffalo General Medical Center

Buffalo, New York, 14203, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Vermont

Burlington, Vermont, 05401, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2P4, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

Prednisone; Steroids; Sugars

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)

Pregnadienediols; Pregnadienes; Pregnanes; Fused-Ring Compounds; Polycyclic Compounds; Carbohydrates

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed

Results Point of Contact

• Title: Dr. Benatar
• Organization: University Of Miami

MBenatar@med.miami.edu

305-243-6480

Study Officials

• Michael Benatar, MBChB, DPhil

  University of Miami

  PRINCIPAL INVESTIGATOR

• Gil Wolfe, MD

  State University of New York at Buffalo

  STUDY DIRECTOR

• Donald Sanders, MD

  Duke University

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MBChB, DPhil

Study Record Dates

• First Submitted: October 14, 2009
• First Posted: October 15, 2009
• Study Start: December 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: June 2, 2017
• Results First Posted: November 2, 2015

Record last verified: 2017-05

Locations

US (8); CA (2)