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

University Eye Hospital, Freiburg

Status and phase: Completed; Phase 3

Conditions: Optic Neuritis

Treatments: Drug: Erythropoietin alfa; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT01962571

P000053

DRKS00005298 (Registry Identifier)

01KG1306 (Other Grant/Funding Number)

2013-002515-10 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 108 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Patients eligible for inclusion in this trial must meet all of the following criteria:

1. Written informed consent obtained according to international guidelines and local laws
2. Male and female patients aged ≥ 18 to ≤ 50 years
3. Patients with ON
4. First symptoms of ON ≤ 10 days prior to the first administration of investigational product
5. High contrast visual acuity (HCVA) of ≤ 0.5 (decimal system)
6. Adequate OCT measurements available

Patients eligible for this trial must not meet any of the following criteria:

1. Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial

2. 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

3. Refractive anomalies: Hyperopia > 5 dpt, myopia < -7 dpt, astigmatism > 3 dpt

4. Media opacity

5. Severe papillitis

6. Previous ON

7. Any other optic nerve and retinal disease

8. Pre-existing MS or any other neurological disease

9. Congenital diseases:

   • thrombophilia
   • phenylketonuria

10. 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

11. Performing semi-professional or professional sporting activities or physical training

12. Pre-treatment with corticosteroids in the last 30 days prior to the onset of optic neuritis

13. Pre-treatment with EPO

14. Known or persistent abuse of medication, drugs or alcohol

15. Active immunization within 2 weeks prior to randomisation

16. Significant surgery within 4 weeks prior to randomisation

17. Blood donation or bloodletting within 4 weeks prior to screening

18. Pre-treatment with immunosuppressive or immunomodulatory agents

19. 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:

20. Current or planned pregnancy; nursing period within 3 months from investigational product administration

21. 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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108 participants in 2 patient groups, including a placebo group

Erythropoietin alfa

Experimental group

Description:

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.

Treatment:

Drug: Erythropoietin alfa

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo