Safety and Efficacy Study of Erythropoietin as Add-on Therapy of Methylprednisolone to Treat Acute Optic Neuritis

Condition(s) targeted: Optic Neuritis

Intervention: Erythropoietin (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Institut fuer anwendungsorientierte Forschung und klinische Studien gGmbH

Official(s) and/or principal investigator(s):
Ricarda Diem, PD MD, Study Director, Affiliation: Department of Neurology University Hospital of the Saarland, Germany

Overall contact:
Ricarda Diem, PD MD, Phone: +49 6841 1624040, Email: ricarda.diem@uniklinikum-saarland.de

The purpose of this study is to determine the safety and efficacy of erythropoietin as an add-on therapy to methylprednisolone in subjects with acute autoimmune optic neuritis.

Official title: Double Blind, Placebo-Controlled Study to Determine the Safety and Efficacy of Erythropoietin as an Add-on Therapy of Methylprednisolone in Subjects With Acute Optic Neuritis (VISION PROTECT)

Study design: Prevention, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: nerve fiber loss in the optical nerve head determined by optical coherence tomography at weeks 4,8 and 16 compared to baseline measurements at baseline and week 16 are used to calculate estimates for changes and differences between the groups.

Secondary outcome: Visual acuity and visual field perception determined at weeks 1, 4, 8, 16 compared to baseline (week 0) MRI measurements of optic nerve atrophy performed at weeks 4, 8 and 16 compared to baseline (week 0)

Detailed description: SUMMARY This study is a multicenter, double-blind, placebo-controlled, parallel-group study to determine the safety and efficacy of erythropoietin (Epo) as an add-on therapy to methylprednisolone (Mpred) in subjects with acute autoimmune optic neuritis.

The primary study endpoint is nerve fiber loss in the optical nerve head determined by optical coherence tomography at weeks 4, 8, and 16 compared to baseline.

Further study objectives include visual acuity, visual field perception, optic nerve atrophy determined by magnetic resonance imaging (MRI), and recovery of visual evoked potentials (VEPs).

A number of 40 subjects will be randomized in equal numbers into one of the two treatment groups.

Treatment groups:

Both Treatment group Mpred 1000 mg/250 ml normal saline i. v. once daily for 3 days Add-on regimen E (Epo): 3. 3 x 104 IU recombinant human Epo given i. v. once daily for 3 days as a bolus injection

Placebo controlled group S (Saline):Normal saline given i. v.once daily for 3 days as a bolus injection

Men and women between the ages of 18 and 45, inclusive, diagnosed with acute unilateral optic neuritis with or without prior diagnosis of multiple sclerosis (according to McDonald criteria; Polman et al., 2005) will be considered for inclusion into the study. Those subjects must have a decreased visual acuity on the affected eye to 0. 5 or less and must have signed written informed consent. While safety will be monitored during the study, an efficacy evaluation will be done after all subjects have completed week 16.

Each subject included in the study will be seen by a treating neurologist and an examining neurologist as well as by an examining ophthalmologist. The treating neurologist will function as the primary treating physician and conduct all subject safety assessments. The examining ophthalmologist and the examining neurologist will conduct all evaluations of vision/optical nerve head atrophy and neurological symptoms, respectively, but will not be involved in any other aspect of patient care. A neurophysiologist will perform measurements of VEPs. MRIs will be performed by a neuroradiologist.

Minimum age: 18 Years. Maximum age: 45 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

To be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of randomization:

- Must give written informed consent and authorize the release and use of protected

health information (PHI).

- Must be 18 to 45 years old, inclusive, at the time of informed consent.

- Must have acute unilateral optic neuritis with or without prior diagnosis of MS

(according to McDonald criteria).

- Symptoms related to optic neuritis must exist for no longer than 10 days prior to

inclusion.

- Must have had normal visual acuity on both eyes before and no history of optic

neuritis.

- Must have a decreased visual acuity on the affected eye to 0. 5 or less at screening.

Exclusion Criteria:

Candidates will be excluded from study if any of the following exclusion criteria exist at the time of randomization:

Medical history:

- Abnormal laboratory results or clinical signs indicative of any significant cardiac,

endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal, neurological (other than MS), and/or other major disease.

- History of prior optic neuritis on the affected or non-affected eye.

- History of squint or amblyopia on either side.

- Hyperopia > 3dptr on either side.

- Myopia < -5dptr on either side.

- Astigmatism > 2dptr on either side.

- Horizontal cup disc ratio > 0. 5 on either side.

- Retinal nerve fiber layer thickness outside normal values (with respect to the OCT

data base).

- Ocular diseases effecting visual acuity or visual fields (cataract, glaucoma,

maculadegeneration, diabetic retinopathy, retinal heredodegeneration or others).

- History of elevated blood pressure.

- Systolic blood pressure of > 159 mmHg, diastolic blood pressure > 99 mmHg at screening

examination.

- History of thromboembolic events.

- Frequent thromboembolic events in 1st grade family members.

- Significant surgery within the 4 weeks prior to randomization.

- Body weight > 100 kg.

- History of severe allergic or anaphylactic reactions after administration of Epo.

- History of malignancy.

- History of seizures.

- Tuberculosis with ongoing or unknown activity.

- Acute gastrointestinal ulceration within the last three months.

- Acute virus, bacterial or fungus infection.

- Infection with HIV, HBV, or HCV.

- History of colitis ulcerosa, diverticulitis, or acute enteroanastomosis.

- Severe osteoporosis.

- Active immunization within 2 weeks prior to inclusion.

- Diagnosis of phenylketonuria.

- Implanted cardiac pacemaker or other non MRI-compatible metallic body implants.

- History of drug or alcohol abuse (as defined by the investigator) within 2 years prior

to randomization.

- Any of the following abnormal blood tests at screening: alanine transaminase/serum

glutamate-pyruvate transaminase (AST/SGPT), or aspartate transaminase/serum glutamicoxaloacetic transaminase (AST/SGOT), gamma-glutamyl-transferase (GGT), or serum creatinine > 2 times the upper limit of normal; hematocrit > the upper limit of normal.

Treatment history

- Prior treatment with cyclosporine, mitoxantrone, methotrexate, cyclophosphamide or

other immunosuppressive agents.

- Treatment with corticosteroids or Epo within 30 days prior to randomization.

Miscellaneous

- Female subjects considering becoming pregnant while in the study.

- Female subjects who are currently pregnant or breast-feeding.

- Previous participation in this study or any other investigational drug study within

the last four weeks.

- Current enrollment in any other investigational drug study.

- Unwillingness or inability to comply with the requirements of the protocol including

the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the protocol.

- Any other reasons that, in the opinion of the investigator, the subject is determined

to be unsuitable for enrollment in this study.

Ricarda Diem, PD MD, Phone: +49 6841 1624040, Email: ricarda.diem@uniklinikum-saarland.de

University Hospital of Hamburg-Eppendorf (Institut of Neuroimmunology and Clinical MS Research (INIMS)), Hamburg 20246, Germany; Not yet recruiting
Christoph Heesen, MD PD, Phone: +49 40428032794, Email: heesen@uke.uni-hamburg.de
Christoph Heesen, MD PD, Principal Investigator

Department of Neurology University Hospital Goettingen, Goettingen, Niedersachsen 37075, Germany; Recruiting
Muriel Sättler, MD, Phone: +49-551-3912837, Email: msaettl@gwdg.de
Muriel Sättler, MD, Principal Investigator

Department of Neurology University Hospital of the Saarland, Germany, Homburg, Saarland 66421, Germany; Recruiting
Ricarda Deam, MD, PD, Phone: +49 6841 1624040, Email: ricarda.diem@uniklinikum-saarland.de
Ricarda Diem, PD MD, Principal Investigator

Related publications:

Maier K, Rau CR, Storch MK, Sattler MB, Demmer I, Weissert R, Taheri N, Kuhnert AV, Bahr M, Diem R. Ciliary neurotrophic factor protects retinal ganglion cells from secondary cell death during acute autoimmune optic neuritis in rats. Brain Pathol. 2004 Oct;14(4):378-87.

Starting date: August 2006
Ending date: December 2008
Last updated: March 12, 2008