Optic Neuritis
Conditions
Brief summary
The main objective of the study is to determine whether glatiramer acetate 20 mg once daily reduces the amount of axonal loss in the optic nerve after a first event of acute optic neuritis compared to placebo patients and to generate data supporting the potential neuroprotective effect of glatiramer acetate in a human in vivo model of axonal loss.
Interventions
DRUGGlatiramer Acetate
20 mg injected daily subcutaneously
DRUGplacebo
injected daily subcutaneously
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Age: 18 - 45 years * Isolated, unilateral, first acute optic neuritis (AON) event consistent with inflammatory demyelinization, not explained by other etiologies. Onset of AON is defined by the presentation of visual disturbances. * Able to provide written informed consent prior to enrollment * Willing and able to comply with the protocol requirements for the duration of the study * For women of child bearing potential: * A negative urine pregnancy test o * Willing to practice an acceptable method of birth control • * Willing to receive a steroidal regimen
Exclusion criteria
* A diagnosis of clinically definite multiple sclerosis (MS) (Clinically Definite Multiple Sclerosis) * Current use of any approved disease modifying agents for treatment of MS * Prior clinical episode of optic neuritis in either eye * Bilateral AON * Inability to undergo study evaluations in both eyes * Known ocular or neurological conditions or abnormalities other than refractive error that impair visual function * Retrogeniculate visual loss * Refractive error of greater than +6 or -6 diopters * Neuromyelitis Optica (Devic's disease) * Systemic diseases that cause inflammatory optic neuropathy, including but not limited to Sarcoidosis, Systemic lupus erythematosus (SLE), Wegener's Granulomatosis, Syphilis, human immunodeficiency virus (HIV) * Known ocular conditions that preclude dilation * Any condition that may interfere with performance of Optical Coherence Tomography (OCT): corneal, lens or fundoscopic abnormality, a co-morbid ocular condition not related to optic neuritis as detected on the OCT reading * Any condition that precludes administration of Glatiramer Acetate, such as a known history of sensitivity to mannitol * Diabetes Mellitus Types I or II * Gastric bypass surgery * Current use of chemotherapy or radiotherapy * Treatments that may cause visual loss such as plaquenil, anti-tubercular agents, interferon (IFN)-alpha therapy, monoclonal antibodies Cardiac medications that may affect visual evaluations such as digitalis, amiodarone, quinine * Ongoing treatment with steroids (for longer than 10 days) within the last 3 months * Significant or unstable medical, systemic, psychiatric or logistical condition that affects the patient's ability to give informed consent or to complete the study procedures * Use of an investigational drug within 30 days prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Retinal Nerve Fiber Layer Thickness at Baseline and Month 6 | Baseline and Month 6 | Axonal loss in the optic nerve (due to optic neuritis) was assessed by measuring retinal nerve fiber thickness of the affected eye using optical coherence tomography (OCT) at Baseline and Month 6. |
Secondary
| Measure | Time frame |
|---|---|
| To Evaluate Changes on Additional OCT Parameters and Other Visual Function and Clinical Parameters. | 6 months |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Glatiramer Acetate Participants received glatiramer acetate 20 mg subcutaneous injection once a day for up to 6 months. | 20 |
| Placebo Participants received placebo subcutaneous injection once a day for up to 6 months. | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Discontinued at Randomization | 2 | 2 |
| Overall Study | Lost to Follow-up | 2 | 5 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Serious Adverse Event | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Glatiramer Acetate | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 31.7 years STANDARD_DEVIATION 7.1 | 34.4 years STANDARD_DEVIATION 6.5 | 33.0 years STANDARD_DEVIATION 6.9 |
| Race/Ethnicity, Customized Asian | 2 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Black/African American | 1 participants | 3 participants | 4 participants |
| Race/Ethnicity, Customized Caucasian | 13 participants | 15 participants | 28 participants |
| Race/Ethnicity, Customized Hispanic | 3 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized Other | 1 participants | 1 participants | 2 participants |
| Sex: Female, Male Female | 13 Participants | 15 Participants | 28 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 1 / 20 | 0 / 20 |
Outcome results
Primary
Retinal Nerve Fiber Layer Thickness at Baseline and Month 6
Axonal loss in the optic nerve (due to optic neuritis) was assessed by measuring retinal nerve fiber thickness of the affected eye using optical coherence tomography (OCT) at Baseline and Month 6.
Time frame: Baseline and Month 6
Population: The modified ITT intent-to-treat (mITT) analysis set included all patients who had been randomized to the study, received at least one dose of study drug, had a baseline OCT evaluation, and had at least one non-missing post-baseline OCT evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glatiramer Acetate | Retinal Nerve Fiber Layer Thickness at Baseline and Month 6 | Baseline (n=18, 18) | 128.1 µm | Standard Deviation 11.9 |
| Glatiramer Acetate | Retinal Nerve Fiber Layer Thickness at Baseline and Month 6 | Month 6 (n=13, 13) | 89.5 µm | Standard Deviation 8.9 |
| Placebo | Retinal Nerve Fiber Layer Thickness at Baseline and Month 6 | Baseline (n=18, 18) | 130.5 µm | Standard Deviation 8.9 |
| Placebo | Retinal Nerve Fiber Layer Thickness at Baseline and Month 6 | Month 6 (n=13, 13) | 88.0 µm | Standard Deviation 5.5 |
Secondary
To Evaluate Changes on Additional OCT Parameters and Other Visual Function and Clinical Parameters.
Time frame: 6 months
Population: Enrollment did not meet expectations, and target sample sizes were not met. As a results, the secondary outcome was not analyzed. There were no data collected for this outcome; there is no data to analyze.