Treatment of Optic Neuritis With Erythropoietin: a Randomised, Double-blind, Placebo-controlled Trial

Study Overview
=================
Brief Summary
-----------------
This clinical trial aims at preventing visual dysfunction and optic nerve degeneration associated with autoimmune optic neuritis by systemic i.v. administration of 33.000 IU erythropoietin over 3 days. The primary objective is to determine the efficacy of erythropoietin compared to placebo given as add-on to methylprednisolone as assessed by measurements of retinal nerve fibre layer thickness and low contrast visual acuity 6 months after acute optic neuritis.

Official Title
-----------------
Treatment of Optic Neuritis With Erythropoietin: a Randomised, Double-blind, Placebo-controlled Trial

Conditions
-----------------
Optic Neuritis

Intervention / Treatment
-----------------
* Drug: Erythropoietin alfa
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Patients eligible for inclusion in this trial must meet all of the following criteria: Written informed consent obtained according to international guidelines and local laws Male and female patients aged ≥ 18 to ≤ 50 years Patients with ON First symptoms of ON ≤ 10 days prior to the first administration of investigational product High contrast visual acuity (HCVA) of ≤ 0.5 (decimal system) Adequate OCT measurements available Patients eligible for this trial must not meet any of the following criteria: Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial Simultaneous participation in another interventional trial which could interfere with this trial and/or participation in a clinical trial within the last 3 months before enrolment in this trial Refractive anomalies: Hyperopia > 5 dpt, myopia < -7 dpt, astigmatism > 3 dpt Media opacity Severe papillitis Previous ON Any other optic nerve and retinal disease Pre-existing MS or any other neurological disease Congenital diseases: thrombophilia phenylketonuria Acquired diseases: autoimmune diseases, cardiovascular diseases, diabetes mellitus, uncontrolled hypertension (with blood pressure > 140 / 90 mm Hg (cf. chapter 7.7.5)), any malignancy, epilepsy, known tuberculosis with ongoing or unknown activity, acute gastrointestinal ulceration within the last 3 months prior to randomisation, acute viral, bacterial or fungal infection, known infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus, or Hepatitis C Virus, history of colitis ulcerosa, diverticulitis, or acute enteroanastomosis, known osteoporosis, history of thromboembolic events, elevated haemoglobin level (>17 g/dl in men or >15 g/dl in women) polycythaemia any other significant illness potentially interfering with any trial assessment or trial treatment Performing semi-professional or professional sporting activities or physical training Pre-treatment with corticosteroids in the last 30 days prior to the onset of optic neuritis Pre-treatment with EPO Known or persistent abuse of medication, drugs or alcohol Active immunization within 2 weeks prior to randomisation Significant surgery within 4 weeks prior to randomisation Blood donation or bloodletting within 4 weeks prior to screening Pre-treatment with immunosuppressive or immunomodulatory agents Persons who are in a relationship of dependence/employment with the sponsor or the investigator This section concerns only female patients who are able to have a child: Current or planned pregnancy; nursing period within 3 months from investigational product administration Unwillingness to use one of the following safe combination methods of contraception within 3 months from investigational product administration to achieve a PEARL index of <1: female condom, diaphragm or coil, each used in combination with a spermicide; hormonal intra-uterine device or hormonal contraception in combination with a mechanical method of contraception

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erythropoietin alfa<br>Recombinant human EPO (Epoetin alfa HEXAL®) will be given as an i.v. bolus injection on days 1, 2 and 3. The dosage per day will be 33.000 IU in accordance with previous trials. | Drug: Erythropoietin alfa<br> <br> |
| Placebo Comparator: Placebo<br>As matched placebo for this study, sterile normal saline (0.9% sodium chloride for i.v. administration) will be used. It will be given as a bolus injection in the same manner as EPO. | Drug: Placebo<br> <br> * Other names: Saline;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global retinal nerve fibre layer thickness (RNFLT-G) | Determination of the efficacy of erythropoietin compared to placebo given as add-on to methylprednisolone (standard of care) as assessed by measurement of global retinal nerve fibre layer thickness (RNFLT-G) in the affected eye 6 months after randomisation. | 6 months | 
| Low contrast visual acuity (LCVA) | Determination of the efficacy of erythropoietin compared to placebo given as add-on to methylprednisolone (standard of care) as assessed by measurement of low contrast visual acuity (LCVA) in the affected eye 6 months after randomisation. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute values of the global retinal nerve fibre layer thickness |  | 6 months | 
| Retinal nerve fibre layer thickness in the papillomacular bundle |  | 6 months | 
| Retinal nerve fibre layer thickness in the temporal quadrant |  | 6 months | 
| Total macular volume |  | 6 months | 
| Visual acuity |  | 6 months | 
| Contrast sensitivity |  | 6 months | 
| Mean visual field defect |  | 6 months | 
| Latency [ms] and amplitude [µV] of visual evoked potentials (VEP) |  | 6 months | 
| Expanded Disability Status Scale (EDSS) score |  | 6 months | 
| Quality of life | Determined by NEI-VFQ-25 | 6 months | 
| Safety | Assessment of AEs / SAEs | Screening until end of study | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Optic neuritis, Multiple Sclerosis, Clinically isolated syndrome, Erythropoietin