Trial of Befizal® 200 mg for the Treatment of Leber Hereditary Optic Neuropathy (Béfinohl)

• ClinicalTrials.gov Identifier: NCT04561466
• Recruitment Status: Recruiting
• First Posted: September 23, 2020
• Last Update Posted: February 12, 2021
• Sponsor: Hôpital Necker-Enfants Malades
• Collaborators: European Georges Pompidou Hospital; CLAIROP
• Information provided by (Responsible Party): Christophe Orssaud, Hôpital Necker-Enfants Malades

Study Description

Brief Summary:

Study of the efficiency of Béfizal® 200 mg in 14 adult patients with a LHON that occurred for less than 5 years. Patient must have certain specific mutations

Condition or disease	Intervention/treatment	Phase
Safety Issues; Efficacy, Self	Drug: Béfizal	Phase 2; Phase 3

Detailed Description:

Study of the efficiency of Béfizal® 200 mg in 14 adult patients in whom the diagnosis of LHON obtained on anamnestic, clinical and ancillary testing / laboratory data. LHON should have occurred for less than 5 years and must be genetically proved with a 3460 or 11778 mitochondrial DNA mutation. Given the mode of transmission, genetic research may have been carried out in a maternal relative

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: open
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Study of Efficacy of Befizal® 200 mg for the Treatment of Leber Hereditary Optic Neuropathy
• Actual Study Start Date: March 26, 2019
• Estimated Primary Completion Date: December 9, 2022
• Estimated Study Completion Date: March 10, 2023

Arms and Interventions

Arm

Intervention/treatment

Experimental: treatment group; 14 adult patients in whom the diagnosis of LHON obtained on anamnestic, clinical and ancillary testing / laboratory data. LHON should have occurred for less than 5 years and must be genetically proved with a 3460 or 11778 mitochondrial DNA mutation. Given the mode of transmission, genetic research may have been carried out in a maternal relative. Befizal® 200 mg will be tested for one year

Drug: Béfizal; 600 mf befizal a day for one year

Outcome Measures

Primary Outcome Measures :

1. Evolution of best corrected farsight visual acuity (in LogMAR) [ Time Frame: Month12 ]
   Measurement of the best corrected farsight visual acuity by Early Treatment Diabetic Retinopathy Study type scale (range from -0.3 to 2.6) -0.3 is the best vision and 2.6 the worse

Secondary Outcome Measures :

1. Farsight best corrected visual acuity [ Time Frame: Month 3 ]
   Measurement of the Farsight best corrected visual acuity in LogMAR by Early Treatment Diabetic Retinopathy Study type scale (range from -0.3 to 2.6) -0.3 is the best vision and 2.6 the worse
2. Evolution of Farsight best corrected visual acuity [ Time Frame: Month 6 ]
   Measurement of the Farsight best corrected visual acuity in LogMAR by Early Treatment Diabetic Retinopathy Study type scale (range from -0.3 to 2.6) -0.3 is the best vision and 2.6 the worse
3. Evolution of Farsight best corrected visual acuity [ Time Frame: Month 9 ]
   Measurement of the Farsight best corrected visual acuity in LogMAR by Early Treatment Diabetic Retinopathy Study type scale (range from -0.3 to 2.6) -0.3 is the best vision and 2.6 the worse
4. Evolution of Farsight best corrected visual acuity [ Time Frame: Month 15 ]
   Measurement of the Farsight best corrected visual acuity in LogMAR by Early Treatment Diabetic Retinopathy Study type scale (range from -0.3 to 2.6) -0.3 is the best vision and 2.6 the worse
5. Evolution of Farsight best corrected visual acuity [ Time Frame: Month 3 ]
   Measurement of the Farsight best corrected visual acuity by Early Treatment Diabetic Retinopathy Study type scale (range from -0.3 to 2.6) -0.3 is the best vision and 2.6 the worse
6. Evolution of Farsight decimal best corrected visual acuity [ Time Frame: Month 6 ]
   Measurement of the Farsight best corrected visual acuity (in LogMAR) measured with a Monoyer scale (range from 20/20 to light perception). 20/20 is the best vision and light perception the worse
7. Evolution of Farsight decimal best corrected visual acuity [ Time Frame: Month 9 ]
   Measurement of the Farsight best corrected visual acuity (in LogMAR) measured with a Monoyer scale (range from 20/20 to light perception). 20/20 is the best vision and light perception the worse
8. Evolution of Farsight decimal best corrected visual acuity [ Time Frame: Month 12 ]
   Measurement of the Farsight best corrected visual acuity (in LogMAR) measured with a Monoyer scale (range from 20/20 to light perception). 20/20 is the best vision and light perception the worse
9. Evolution of Farsight decimal best corrected visual acuity [ Time Frame: Month 15 ]
   Measurement of the Farsight best corrected visual acuity (in LogMAR) measured with a Monoyer scale (range from 20/20 to light perception). 20/20 is the best vision and light perception the worse
10. Evolution of Nearsight visual acuity [ Time Frame: Month 3 ]
    Measurement of the best corrected nearsight visual acuity measured using a Parinaud scale (from P48 to P1>.5) P48 is the worse vision and P1.5 the best
11. Evolution of Nearsight visual acuity [ Time Frame: Month 6 ]
    Measurement of the best corrected nearsight visual acuity measured using a Parinaud scale (from P48 to P1>.5) P48 is the worse vision and P1.5 the best
12. Evolution of Nearsight visual acuity [ Time Frame: Month 9 ]
    Measurement of the best corrected nearsight visual acuity measured using a Parinaud scale (from P48 to P1>.5)P48 is the worse vision and P1.5 the best
13. Evolution of Nearsight visual acuity [ Time Frame: Month 12 ]
    Measurement of the best corrected nearsight visual acuity measured using a Parinaud scale (from P48 to P1>.5) P48 is the worse vision and P1.5 the best
14. Evolution of Nearsight visual acuity [ Time Frame: Month 15 ]
    Measurement of the best corrected nearsight visual acuity measured using a Parinaud scale (from P48 to P1>.5) P48 is the worse vision and P1.5 the best
15. Evolution of retinal nerve fibers layer Optical Coherent Tomography [ Time Frame: Month 6 ]
    physiological parameter : Optical Coherent Tomography
16. Evolution of retinal nerve fibers layer Optical Coherent Tomography [ Time Frame: Month 12 ]
    physiological parameter : Optical Coherent Tomography
17. automated visual field measurement [ Time Frame: Month 3 ]
    physiological parameter : automated visual field corrected deviation of a visual field, measured according to a protocol STAT protocol 30 (Champ visuel Métrovision, Perenchies, France)
18. automated visual field measurement [ Time Frame: Month 6 ]
    physiological parameter : automated visual field
19. automated visual field [ Time Frame: Month 9 of a treatment with BEFIZAL® 200mg (ARROW GENERIQUES) compare to Month 0 ]
    physiological parameter : automated visual field corrected deviation of a visual field, measured according to a protocol STAT protocol 30 (Champ visuel Métrovision, Perenchies, France)
20. automated visual field measurement [ Time Frame: Month 12 ]
    physiological parameter : automated visual field corrected deviation of a visual field, measured according to a protocol STAT protocol 30 (Champ visuel Métrovision, Perenchies, France)
21. automated visual field measurement [ Time Frame: Month 15 ]
    physiological parameter : automated visual field corrected deviation of a visual field, measured according to a protocol STAT protocol 30 (Champ visuel Métrovision, Perenchies, France)
22. Manual visual field measurement [ Time Frame: Month 3 ]
    physiological parameter : manual visual field measured with isopters V / 4, III / 1 and II / 1
23. Manual visual field measurement [ Time Frame: Month 6 ]
    physiological parameter : manual visual field measured with isopters V / 4, III / 1 and II / 1
24. Manual visual field measurement [ Time Frame: Month 9 ]
    physiological parameter : manual visual field measured with isopters V / 4, III / 1 and II / 1
25. Manual visual field measurement [ Time Frame: Month 12 ]
    physiological parameter : manual visual field measured with isopters V / 4, III / 1 and II / 1
26. Manual visual field measurement [ Time Frame: Month 15 ]
    physiological parameter : manual visual field measured with isopters V / 4, III / 1 and II / 1
27. National Eye Institute Visual Function Questionnaire 25 [ Time Frame: Month 12 ]
    Questionnaire
28. Concentration of serum creatinine [ Time Frame: Every three months until Month 15 ]
    Concentration of serum creatinine
29. Concentration of high-density lipoprotein cholesterol [ Time Frame: Every three months until Month 15 ]
    Blood test
30. Concentration of very low-density lipoprotein cholesterol [ Time Frame: Every three months until Month 15 ]
    Blood test
31. Concentration of triglycerides [ Time Frame: Every three months until Month 15 ]
    Blood test
32. Rate of Partial thromboplastin time [ Time Frame: Every three months until Month 15 ]
    Blood test
33. Concentration of Aspartate aminotransférase [ Time Frame: Every three months until Month 15 ]
    Blood test
34. Concentration of Alanine aminotransférase [ Time Frame: Every three months until Month 15 ]
    Blood test
35. Concentration of lactate deshydrogenase [ Time Frame: Every three months until Month 15 ]
    Blood test
36. Concentration of creatine kinase [ Time Frame: Every three months until Month 15 ]
    Blood test

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Adult patients in whom the diagnosis of LHON obtained on anamnestic, clinical and ancillary testing / laboratory data. LHON should have occurred for less than 5 years and must be genetically proved with a 3460 or 11778 mitochondrial DNA mutation. Given the mode of transmission, genetic research may have been carried out in a maternal relative

Exclusion Criteria:

• * Any optic neuropathy for which the diagnosis of LHON is not formally confirmed or genetically proven;

  • LHON that started for more than 5 years;
  • LHON associated with another primary mutation than 3460 or 11778
  • Children or adult patients under guardianship or deprived of liberty by administrative or judicial decision;
  • Women of childbearing age ; pregnant or lactating women;
  • Patients who do not have affiliation to a social protection scheme (national or private insurance / beneficiary or assignee);
  • Patient who did not give its written, informed and signed consent;
  • Allergy to fibrate, bezafibrate and / or BEFIZAL® 200mg (Arrow Generiques) or one of these constituents;
  • Photosensitivity reactions related to fibrates;
  • Patient already receiving treatment with fibrates or HMG Co-A reductase inhibitors or anticoagulants;
  • Hepatic insuffisiency or dysfunction with increased of transaminases (AST and ALT) over 3 times of the normal;
  • Renal insufficiency with serum creatinine> 15 mg / L (> 135 mg / dL) Biliary pathology

Contacts and Locations

Contacts

Contact: christophe Orssaud, MD; 33 1 56 09 34 66; christophe.orssaud@aphp.fr

Locations

France

HEGP Hospital; Recruiting

Paris, France, 75015

Contact: Christophe ORSSAUD, MD 33 1 56 09 34 98 christophe.orssaud@aphp.fr

Contact: Dominique Bremond Gignac, MD PhD 33 1 44 49 45 02 dominique.bremond@aphp.fr

Sponsors and Collaborators

Hôpital Necker-Enfants Malades

European Georges Pompidou Hospital

CLAIROP

Investigators

• Study Chair: Dominique Bremond Gignac, MD PhD; Necker Hopsital

More Information

• Responsible Party: Christophe Orssaud, Principal investigator, Hôpital Necker-Enfants Malades
• ClinicalTrials.gov Identifier: NCT04561466
• Other Study ID Numbers: beza16
• First Posted: September 23, 2020
• Last Update Posted: February 12, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Christophe Orssaud, Hôpital Necker-Enfants Malades:

leber herediatry optic neuropathy; befizal

Additional relevant MeSH terms:

Bezafibrate; Optic Nerve Diseases; Optic Atrophy, Hereditary, Leber; Cranial Nerve Diseases; Nervous System Diseases; Eye Diseases; Optic Atrophies, Hereditary; Optic Atrophy; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Eye Diseases, Hereditary; Genetic Diseases, Inborn; Mitochondrial Diseases; Metabolic Diseases; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents