Gene Therapy Clinical Trial for the Treatment Of Leber's HereDitary Optic Neuropathy

Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age12-75
SponsorWuhan Neurophth Biotechnology Limited Company

About this trial

The objective of this clinical study is to select the optimal dose and evaluate the safety and efficacy of NR082 in treatment of LHON caused by mitochondrial ND4 gene mutation. Part 1 (Phase 1/2) is a safety dose-finding study, which will enroll subjects aged ≥ 18 years old and ≤ 75 years old to receive a single unilateral intravitreal (IVT) injection of NR082 to observe its safety and efficacy. In Part 2 (Phase 3) of the clinical study, the dose recommended after the end of Part 1 is used to further verify the safety and efficacy of the study drug. Part 2 of the study is divided into the safety run-in phase and the randomized, double-blind and control study. Subjects aged ≥ 12 years and ≤ 75 years will be enrolled in the Part 2. The run-in phase will enroll 6 evaluable subjects. After monitoring for at least 6 weeks, if no new safety signals are observed, the clinical trial will enter the randomized, double-blind and control study phase upon approval by the Safety Review Committee(SRC). The clinical manifestation of all subjects is reduced visual acuity caused by LHON associated with ND4 mutation, and central laboratory test showed G11778A mutation (a CLIA-certified laboratory), while the reduced visual acuity lasted for \> 6 months and \< 10 years.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age at signing of informed consent form

In Part 1, the age of the subjects must be ≥ 18 years old and ≤ 75 years old

In Part 2, the age of the subjects must be ≥ 12 years old and ≤ 75 years old, and the 6 evaluable subjects must be monitored for at least 6 weeks during the safety run-in phase. If SRC believes that there is no safety issue, the randomized double-blind control study will be initiated Subject Type and Disease Characteristics

The clinical manifestation caused by LHON is vision loss, with a visual acuity of ≥ 0.5 LogMAR in BCVA in either eye

Disqualifiers

Any known allergy and/or hypersensitivity to the study drug or its constituents

Contraindication to IVT injection in any eye

IVT drug delivery to any eye within 30 days prior to the screening visit

History of vitrectomy in either eye

Trial design

Design model

Sequential

Treatments tested in this trial

  • NR082 injection

    Drug

    Intravitreal injection(IVT)

  • Sham Injection

    Device

    Sham Intravitreal Injection

Treatment groups

102 Participants
are divided into 2 treatment groups
Group A: NR082 injectionExperimental treatment 1 intervention
Group B: sham-injectionSham comparator 1 intervention

Trial outcomes

Primary outcomes

1

Safety and tolerability of NR082 at different doses

Incidence rates of AEs, SAEs and DLTs within 12 weeks after injection of NR082 at different doses

Time frame
Part 1 (Phase1/2): 12 weeks
2

Safety after NR082 treatment among subjects 12 ≤ aged ≤ 75 years

Incidence rates of AEs and SAEs within 6 weeks after NR082 treatment

Time frame
Part 2 (Stage 1) : 6 weeks
3

Efficacy of NR082 in study eye

Proportion of ≥ 0.3 LogMAR from baseline in BCVA in the study eye in the NR082 treatment and the sham-injection at Week 52 after treatment

Time frame
Part 2 (Stage 2): 52 weeks

Secondary outcomes

1

The efficacy and safety following intravitreal injection of NR082 at different doses

Improvent and mean change from baseline in BCVA; Change from baseline in visual field, contrast sensitivity and visual evoked potential

Time frame
Part 1 (Phase1/2), Part 2 (Stage 1 and Stage 2): Week 2, 6, 12, 26, 40 and 52
2

Further assess the efficacy and safety following intravitreal injection of NR082 at different doses

Descriptions of safety evaluation at Weeks 26, 40 and 52

Time frame
Part 1 (Phase1/2) and Part 2 (Stage 1): At Weeks 26, 40 and 52
3

Immunogenicity and vector shedding/biodistribution

Assessment of cell immunity, humoral immunity, vector DNA shedding in tears (both eyes) and biodistribution in whole blood

Time frame
Part 1 (Phase1/2), Part 2 (Stage 1 and Stage 2): Week 2, 6, 12, 26, 40 and 52
4

The change in quality of life from baseline

Change from baseline in VFQ-25 and SF-36

Time frame
Part 1 (Phase1/2), Part 2 (Stage 1 and Stage 2): Week 2, 26 and 52

Other outcomes

Sponsors and contacts

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