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

Optic Neuritis Clinical Trial

— TONE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01962571
• Other study ID #: P000053
• Secondary ID: 2013-002515-10DR
• Status: Completed
• Phase: Phase 3
• Start date: November 25, 2014
• Est. completion date: November 26, 2019

Study information

• Verified date: November 2019
• Source: University Eye Hospital, Freiburg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: November 26, 2019
• Est. primary completion date: June 20, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Neuritis
• Optic Neuritis

Intervention

Drug:
• Erythropoietin alfa

• Placebo

Locations

Country	Name	City	State
Germany	Duesseldorf University Hospital	Duesseldorf	Nordrhein-Westfalen
Germany	University Hospital Erlangen	Erlangen	Bayern
Germany	Medical Center - University of Freiburg, Eye Hospital	Freiburg	Baden-Wuerttemberg
Germany	University Medical Center Göttingen	Göttingen	Niedersachsen
Germany	University Medical Center Hamburg-Eppendorf	Hamburg
Germany	Hannover Medical School	Hannover	Niedersachsen
Germany	Heidelberg University Hospital, Department of Neurooncology	Heidelberg	Baden-Wuerttemberg
Germany	University Medical Center of the Johannes Gutenberg University Mainz	Mainz	Rheinland-Pfalz
Germany	University Hospital Klinikum rechts der Isar, Munich	Munich	Bayern
Germany	University Hospital of Munich	Munich	Bayern
Germany	Tuebingen University Hospital	Tuebingen	Baden-Wuerttemberg

Sponsors (2)

Lead Sponsor	Collaborator
University Eye Hospital, Freiburg	German Federal Ministry of Education and Research

Country where clinical trial is conducted

Germany, 

References & Publications (2)

Diem R, Molnar F, Beisse F, Gross N, Drüschler K, Heinrich SP, Joachimsen L, Rauer S, Pielen A, Sühs KW, Linker RA, Huchzermeyer C, Albrecht P, Hassenstein A, Aktas O, Guthoff T, Tonagel F, Kernstock C, Hartmann K, Kümpfel T, Hein K, van Oterendorp C, Grotejohann B, Ihorst G, Maurer J, Müller M, Volkmann M, Wildemann B, Platten M, Wick W, Heesen C, Schiefer U, Wolf S, Lagrèze WA. Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial-study protocol. BMJ Open. 2016 Mar 1;6(3):e010956. doi: 10.1136/bmjopen-2015-010956. — View Citation

Sühs KW, Hein K, Sättler MB, Görlitz A, Ciupka C, Scholz K, Käsmann-Kellner B, Papanagiotou P, Schäffler N, Restemeyer C, Bittersohl D, Hassenstein A, Seitz B, Reith W, Fassbender K, Hilgers R, Heesen C, Bähr M, Diem R. A randomized, double-blind, phase 2 study of erythropoietin in optic neuritis. Ann Neurol. 2012 Aug;72(2):199-210. doi: 10.1002/ana.23573. — View Citation

Outcome

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

External Links

•   Study information and useful links in German language