A Randomized, Double-blind, Placebo-controlled, Multicenter Study of the Effects of Glatiramer Acetate (GA) on the Retinal Nerve Fiber Layer (RNFL) and Visual Function in Patients With a First Episode of Acute Optic Neuritis (AON). (Octagon)

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00856635
• Collaborator: (none)
• Enrollment: 44
• Arms: 2
• Duration (Months): 24

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Optic Neuritis	Drug: Glatiramer Acetate; Drug: placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Multicenter Study of the Effects of Glatiramer Acetate (GA) on the Retinal Nerve Fiber Layer (RNFL) and Visual Function in Patients With a First Episode of Acute Optic Neuritis (AON)
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Glatiramer acetate Participants received glatiramer acetate 20 mg subcutaneous injection once a day for up to 6 months.	Drug: Glatiramer Acetate; 20 mg injected daily subcutaneously; Other Names: Copaxone
Placebo Comparator: Placebo Participants received placebo subcutaneous injection once a day for up to 6 months.	Drug: placebo; injected daily subcutaneously

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. To Evaluate Changes on Additional OCT Parameters and Other Visual Function and Clinical Parameters. [6 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

• Principal Investigator: Mark J. Kupersmith, MD, Roosevelt Hospital
• Principal Investigator: Peter Calabresi, MD, John Hopkins School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT00856635
• Other Study ID Numbers: PM030
• First Posted: Mar 6, 2009
• Last Update Posted: Feb 6, 2018
• Last Verified: Jan 1, 2018

• Additional relevant MeSH terms: Neuritis; Optic Neuritis; Glatiramer Acetate; (T,G)-A-L

Study Results

Participant Flow

Arm/Group Title	Glatiramer Acetate	Placebo
Arm/Group Description	Participants received glatiramer acetate 20 mg subcutaneous injection once a day for up to 6 months.	Participants received placebo subcutaneous injection once a day for up to 6 months.
Period Title: Overall Study
STARTED	22	22
Received Study Drug	20	20
COMPLETED	12	14
NOT COMPLETED	10	8

Baseline Characteristics

Arm/Group Title	Glatiramer Acetate	Placebo	Total
Arm/Group Description	Participants received glatiramer acetate 20 mg subcutaneous injection once a day for up to 6 months.	Participants received placebo subcutaneous injection once a day for up to 6 months.	Total of all reporting groups
Overall Participants	20	20	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.7 (7.1)	34.4 (6.5)	33.0 (6.9)
Sex: Female, Male (Count of Participants)
Female	13 65%	15 75%	28 70%
Male	7 35%	5 25%	12 30%
Race/Ethnicity, Customized (participants) [Number]
Asian	2 10%	0 0%	2 5%
Caucasian	13 65%	15 75%	28 70%
Black/African American	1 5%	3 15%	4 10%
Hispanic	3 15%	1 5%	4 10%
Other	1 5%	1 5%	2 5%

Outcome Measures

1. Primary Outcome

Title	Retinal Nerve Fiber Layer Thickness at Baseline and Month 6
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Glatiramer Acetate	Placebo
Arm/Group Description	Participants received glatiramer acetate 20 mg subcutaneous injection once a day for up to 6 months.	Participants received placebo subcutaneous injection once a day for up to 6 months.
Measure Participants	18	18
Baseline (n=18, 18)	128.1 (11.9)	130.5 (8.9)
Month 6 (n=13, 13)	89.5 (8.9)	88.0 (5.5)

2. Secondary Outcome

Title	To Evaluate Changes on Additional OCT Parameters and Other Visual Function and Clinical Parameters.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Glatiramer Acetate	Placebo
Arm/Group Description	Participants received glatiramer acetate 20 mg subcutaneous injection once a day for up to 6 months. Glatiramer Acetate: 20 mg injected daily subcutaneously	Participants received placebo subcutaneous injection once a day for up to 6 months. placebo: injected daily subcutaneously
Measure Participants	0	0

Adverse Events

Arm/Group Title	Glatiramer Acetate		Placebo
Arm/Group Description	Participants received glatiramer acetate 20 mg subcutaneous injection once a day for up to 6 months.		Participants received placebo subcutaneous injection once a day for up to 6 months.
All Cause Mortality
	Glatiramer Acetate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Glatiramer Acetate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/20 (5%)		0/20 (0%)
Immune system disorders
Drug Hypersensitivity	1/20 (5%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Glatiramer Acetate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)

Limitations/Caveats

Enrollment did not meet expectations, and target sample sizes were not met.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.