A Phase I/IIa gene therapy clinical trial in LHON patients

Phase 1

• Conditions: eber Hereditary Optic Neuropathy due to mutations in the mitochondrial NADH Dehydrogenase 4 gene; MedDRA version: 16.1Level: LLTClassification code 10062951Term: Leber's hereditary optic atrophy neuropathySystem Organ Class: 100000004850; Therapeutic area: Diseases [C] - Eye Diseases [C11]

• Registration Number: EUCTR2013-001405-90-FR
• Lead Sponsor: GENSIGHT-BIOLOGICS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-02-18
• Last Update Posted: 28 September 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

1. Documented diagnosis of LHON based on a genetic test confirming the presence of the G11778A mutation in the mitochondrial ND4
2. Age 18 years old or older at the time of study entry (informed consent signature)
3. Visual acuity = 1/10 of the less functional eye
4. Visual acuity = 3/10 of the less functional eye for the patients of cohort 4 only
5. Sufficient viable retinal ganglion cells (RGC) as determined by optical coherence tomography (OCT): Retinal nerve fiber layer (RNFL) thickness estimation = 80 µm
6. No infection with Human Immunodeficiency Virus (HIV)
7. Negative pregnancy test in women of childbearing potential (a woman who is two years post-menopausal or surgically sterile is not considered to be of childbearing potential)
8. Female patients (if childbearing potency) must agree to use an effective methods of birth control during 6 months after the end of treatment
9. Affiliated to or a beneficiary of the French health care system
10. Written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 22
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

11. Any known allergy or hypersensibility to one of the product used during the trial
12. Contraindication to IVT surgery (anaemia Hb <8g/dl, severe cardiovascular disease, severe coagulopathy…)
13. Disorder of the ocular humors and of the internal retina involving visual disability
14. Glaucoma
15. Presence of other pathology whose symptoms or associated treatments might affect the retina or the optic nerve
16. Vascular retinal occlusion
17. Narrow angle contra-indicating pupillary dilation
18. Other cause of optic neuropathy (inflammatory conditions or exposure to toxins...)
19. Patients presenting known mutation of other genes implicated in pathological retinal conditions
20. Patients treated by oral corticoids within 14 days prior inclusion at study entry.
21. Patients who had received Idebenone during the 2 months preceding the injection.
22. Participation in any other clinical trial on the eye within 3 months preceding the injection and during the study period
23. Patients who had eye surgery within the last 3 months preceding the inclusion
24. Patients suffering from any systemic illness or showing medically significant abnormal laboratory values at screening
25. Absence of vision on the other contralateral eye
26. Patients affected by pathologies for which the symptoms and/or the associated treatments can alter the visual function, for instance cancers or any pathology of the central nervous system
27. Diabetes patients with symptoms of retinopathy or macula oedema,
28. Any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful completion of the study
29. Patient unable or unwilling to comply with the protocol requirements

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified