Ocular Myasthenia Gravis
Conditions
Keywords
Ocular myasthenia gravis, Prednisone, Steroids
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
Detailed description
The purpose of this study is to learn two things about prednisone in patients with ocular myasthenia. The first thing we aim to learn is whether or not prednisone is effective in improving the symptoms of double vision and drooping eyes that are experienced by patients with ocular myasthenia. The second thing we aim to learn is whether we can find a dose of prednisone that is well tolerated and safe. The overall goal is to find out whether a dose of prednisone that is safe and well tolerated is also effective in improving the symptoms of ocular myasthenia. After completing screening assessments to confirm eligibility, all participants will receive treatment with pyridostigmine. If a participant's symptoms do not resolve within the first month while being treated with pyridostigmine, they will be randomized to receive prednisone or placebo. The amount of study medication a participant receives will depend on how their symptoms respond to the medication and if they experience any side effects. After four months, participants that continue to have symptoms of ocular myasthenia and do not have side effects will receive open label high dose prednisone. Participants that no longer have symptoms will taper their dose of study drug in a double-blind fashion.
Interventions
DRUGPlacebo
Placebo dosages will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain matching placebo.
DRUGPrednisone
Prednisone will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain 10mg of prednisone.
Sponsors
University of Miami
University of Rochester
Michael Benatar
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Failure | 4 months | Failure to achive sustatined minimal manifestation status by week 16 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prednisone Corticosteroid
Prednisone: Prednisone will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain 10mg of prednisone.
Pyridostigmine: Prior to randomization, pyridostigmine dosage increments will be made as needed for myasthenic symptoms and as tolerated according to a pre-specified dosage titration schedule. Following randomization, dose will remain constant. | 6 |
| Placebo Matched, inactive substance
Placebo: Placebo dosages will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain matching placebo.
Pyridostigmine: Prior to randomization, pyridostigmine dosage increments will be made as needed for myasthenic symptoms and as tolerated according to a pre-specified dosage titration schedule. Following randomization, dose will remain constant. | 5 |
| Total | 11 |
Baseline characteristics
| Characteristic | Prednisone | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 5 Participants | 11 Participants |
| Age, Continuous | 64 years STANDARD_DEVIATION 18 | 62 years STANDARD_DEVIATION 9 | 63 years STANDARD_DEVIATION 13.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 4 / 5 |
| serious Total, serious adverse events | 1 / 6 | 2 / 5 |
Outcome results
Primary
Treatment Failure
Failure to achive sustatined minimal manifestation status by week 16
Time frame: 4 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prednisone | Treatment Failure | 17 percentage of participants |
| Placebo | Treatment Failure | 100 percentage of participants |
Secondary
Change in Ocular Quantitative Myasthenia Score From Baseline to Week 16
Time frame: 4 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Prednisone | Change in Ocular Quantitative Myasthenia Score From Baseline to Week 16 | -2.25 units on a scale |
| Placebo | Change in Ocular Quantitative Myasthenia Score From Baseline to Week 16 | -0.05 units on a scale |
Comparison: Mean Ocular QMG Changes from Baseline to Week 16 . 95% CI and p-values obtained from the analysis of covariance model to adjust for the baseline value of the outcome variable.p-value: 0.3795% CI: [-7.2, 2.8]ANCOVA
Secondary
Change in Quality of Life as Measured by the 10-Item Neuro-ophthalmological Supplement to the NEI-VFQ-25
Time frame: 4 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Prednisone | Change in Quality of Life as Measured by the 10-Item Neuro-ophthalmological Supplement to the NEI-VFQ-25 | 15.28 units on a scale |
| Placebo | Change in Quality of Life as Measured by the 10-Item Neuro-ophthalmological Supplement to the NEI-VFQ-25 | -1.7 units on a scale |
Comparison: Mean Change NEI-VFQ-25 10 item neuro-opthtalmological supplement score baseline to week 16. 95% CI and p-values obtained from the analysis of covariance model to adjust for the baseline value of the outcome variable.p-value: 0.1695% CI: [-9.22, 43.17]ANCOVA
Secondary
Change in Quality of Life as Measured by the MG-QOL-15 Score
Time frame: 4 Months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Prednisone | Change in Quality of Life as Measured by the MG-QOL-15 Score | -6.3 units on a scale |
| Placebo | Change in Quality of Life as Measured by the MG-QOL-15 Score | -2.5 units on a scale |
Comparison: Mean Change in quality if life as measured by the MG-QOL-15 score at the end of Double- Blinded Treatment. 95% CI and p-values obtained from the analysis of covariance model to adjust for the baseline value of the outcome variable.p-value: 0.1595% CI: [-9.37, 1.75]ANCOVA
Secondary
Change in Quality of Life as Measured by the NEI-VFQ-25 Measures
Time frame: 4 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Prednisone | Change in Quality of Life as Measured by the NEI-VFQ-25 Measures | 10.7 units on a scale |
| Placebo | Change in Quality of Life as Measured by the NEI-VFQ-25 Measures | 4.14 units on a scale |
Comparison: Mean Change in quality of life as measured by the NEI-VFQ-25 at the end of Double- Blinded Treatment. 95% CI and p-values obtained from the analysis of covariance model to adjust for the baseline value of the outcome variable.p-value: 0.1395% CI: [-2.59, 15.71]ANCOVA