Leber Hereditary Optic Neuropathy (LHON)Phase 1/2NCT05293626
Gene Therapy Clinical Trial for the Treatment of Leber's Hereditary Optic Neuropathy Associated With ND4 Mutations
A Phase 1/2 study testing NR082 Injection and Injection needle in people with Leber Hereditary Optic Neuropathy (LHON), run by Neurophth Therapeutics Inc at 3 sites in United States.
Trial summary
The objective of this clinical study is to evaluate the safety and efficacy of NR082 in the treatment of LHON caused by mitochondrial ND4 gene mutation. This study will enroll subjects aged ≥ 18 years old and ≤ 75 years old to receive a single unilateral intravitreal (IVT) injection of NR082 to evaluate its safety and… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Leber Hereditary Optic Neuropathy (LHON)
- What is being tested?
- NR082 Injection and Injection needle
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 3 sitesUnited States
- Study dates
- 22 May 2023to Dec 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age at the time of signing the informed consent form: the age of the subjects must be ≥ 18 years old and ≤ 75 years old.
- The clinical manifested vision loss due to LHON, and any eye BCVA ≥ 0.5 LogMAR
- The genotype testing result shows the presence of G11778A mutation in the ND4 gene, and the absence of the other primary LHON associated mutations in the mitochondrial DNA (mtDNA) (ND1 [G3460A] or ND6 [T14484C]) (confirmed by a CLIA-certified international laboratory
- The vision loss in the eye with worse visual acuity lasted > 6 months and < 10 years at screening
- Pupils can be adequately dilated for a thorough ocular examination and visual acuity test
- Each eye of the subject must maintain at least Hand Motion VA (≤ 2.3 LogMAR) as defined in the ocular/vision examination manual (operating manual for refraction and VA examinations) in this study
Show all 11Show fewer
- Willingness to comply with the clinical study protocol and 5 years of long-term follow-up after administration
- Male or female
- A male subject must agree to take contraceptive measures at least 6 months after the treatment visit;
- A female subject is eligible to participate if she is not pregnant , not breastfeeding, and at least one of the following conditions applies:i)Not a woman of childbearing potential (WOCBP) ;ii) A WOCBP who agrees to follow the contraception guidance for at least 6 months after the treatment visit
- Written informed consent form must be obtained from the subject or his/her parent/legal guardian before any study-related procedures are performed.If the subject is legally blind (> 1.0 LogMAR or the readings of decimal visual acuity chart <0.1), an impartial witness must be present throughout the informed consent process and discussion process.
Who cannot join
- 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
- Narrow anterior chamber angle in any eye contra-indicating pupillary dilation
- Presence of disorders or diseases of the eye or adnexa, excluding LHON, which may interfere with visual or ocular assessments, including spectral-domain optical coherence tomography (SD-OCT), during the study
Show all 22Show fewer
- Presence of known/documented mutations, other than the LHON-related mutation, which are known to cause pathology of the optic nerve, retina or afferent visual system
- Presence of systemic or ocular/vision diseases, disorders, or pathologies, other than LHON, known to cause or be associated with vision loss, or whose associated treatment(s) or therapy(ies) is/are known to cause or be associated with vision loss
- Presence of optic neuropathy from any cause other than LHON
- Presence of illness or disease that, in the opinion of the investigator, include symptoms and/or the associated treatments that can alter visual function, for instance cancers or pathology of the central nervous system (CNS), including multiple sclerosis (diagnosis of multiple sclerosis must be based on the 2010 Revisions to the McDonald Criteria) , and/or diseases or conditions that affect the safety of subjects participating in the study
- History of recurrent uveitis (idiopathic or immune-related) or active ocular inflammation
- Participated in another clinical study and receive an IMP within 90 days prior to the screening visit
- Exceptions: Subjects who have completed the clinical study of idebenone as IMP > 90 days prior to the screening visit and has completely discontinued idebenone at least 7 days prior to dosing are still eligible to participate in the study.
- Any eye has previously received ocular gene therapy
- Subjects who refused to stop using idebenone
- Have undergone ocular surgery of clinical relevance (per investigator's assessment) within 90 days prior to the screening visit
- Female subjects who are breastfeeding or plan to breastfeed within the first 6 months after the administration of NR082 Injection
- History of drug or alcohol abuse (including heavy smoking, i.e., > 20 cigarettes per day or >20 pack-years [equivalent to one pack a day for 20 years or 2 packs a day for 10 years])
- Human immunodeficiency virus (HIV) antibody, syphilis antibody and HCV antibody positive are excluded; hepatitis B test that shows a clinically significant active infection requiring treatment (defined as the presence of hepatitis B core antibody [HBcAb] positive or hepatitis B surface antigen [HBsAg] positive, and hepatitis B virus deoxyribonucleic acid [HBV-DNA]) > 1000 copies/mL or according to local laboratory method above lower limit of quantitative detection) are excluded
- Unable to tolerate (e.g., immunomodulatory regimen) or unable or unwilling to comply with all the protocol requirements
- Subjects from the study site fail to comply with or do not agree to comply with local and institutional guidelines for suspected 2019 novel coronavirus (COVID-19) infection/testing
- Any other exclusions determined by the investigator
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Colorado Health Eye Center
Aurora, Colorado, 80045
Stanford Byers Eye Institute
Palo Alto, California, 94303-5353
Wills Eye Hospital, Neuro Ophthalmology Department
Philadelphia, Pennsylvania, 19107
About this study
Official title: A Phase 1/2, Single-Arm, Open-Label, Dose-Finding Clinical Trial to Evaluate the Safety and Efficacy of Gene Therapy for Leber's Hereditary Optic Neuropathy (LHON) Associated With ND4 Mutation
The objective of this clinical study is to evaluate the safety and efficacy of NR082 in the treatment of LHON caused by mitochondrial ND4 gene mutation. This study will enroll subjects aged ≥ 18 years old and ≤ 75 years old to receive a single unilateral intravitreal (IVT) injection of NR082 to evaluate its safety and efficacy. The clinical manifestations of all subjects are to be reduced visual acuity caused by LHON associated with ND4 mutation, with laboratory test showing G11778A mutation (a CLIA-certified laboratory) and reduced visual acuity lasted for > 6 months and < 10 years.
Read the detailed description
At the dose-finding stage, the principle is that the Safety Review Committee (SRC) will decide whether to make dose adjustment based on the safety data of the starting dose. The starting dose is 1.5×109 vg, 0.05 mL eye/dose.The safety of the starting dose will be reviewed by the SRC, and dose escalation or de-escalation is by recommendation of the SRC.The safety of the starting dose will first be performed in 6 evaluable subjects.
Criteria for Dose Modification:
Dose Escalation:
If drug-related dose-limiting toxicity (DLT) events are observed in ≤ 2 of the 6 evaluable subjects within 6 weeks after the dosing of NR082 at the starting dose, the dose can be escalated to 4.5×109 vg, 0.05 mL eye/dose (high dose) after the approval by SRC.
Dose De-escalation:
If drug-related dose-limiting toxicity (DLT) events are observed in > 2 of the 6 evaluable subjects within 6 weeks after the dosing of NR082 at the starting dose, the dose can be de-escalated to 0.5×109 vg, 0.05 mL eye/dose (low dose) after the approval by SRC.
If drug-related dose-limiting toxicity (DLT) events are observed in > 2 of the 6 evaluable subjects within 6 weeks after the dosing of NR082 at the high dose, the dose can be de-escalated to 3.0×109vg, 0.05 mL eye/dose (intermediate dose) after the approval by SRC.
Enrollment Sequence:
- The enrollment sequence of any dose group (6 subjects) is that the 2nd subject and the 3rd subject will be enrolled at least 7 days after the enrollment of the 1st subject;
- The 4th, 5th and 6th subjects will be enrolled at least 7 days after the enrollment of the 2nd and the 3rd subjects.
The 7-day interval is to avoid acute safety events to the greatest possible extent
- Conditions
- Leber Hereditary Optic Neuropathy (LHON)
- Being tested
- NR082 Injection, Injection needle
- Medical subject headings
- Optic Atrophy, Hereditary, Leber
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NR082 InjectionDrug
The starting dose is 1.5E9 vg, 0.05 mL eye/dose.
Dose Escalation:
If drug-related dose-limiting toxicity (DLT) events are observed in ≤ 2 of the 6 evaluable subjects using the starting dose within 6 weeks after the dosing of NR082, the dose can be escalated to 4.5E9 vg, 0.05 mL eye/dose (high dose) after approval by SRC.
Dose De-escalation： If drug-related dose-limiting toxicity (DLT) events are observed in > 2 of the 6 evaluable subjects using the starting dose within 6 weeks after the dosing of NR082, the dose can be de-escalated to 0.5E9 vg, 0.05 mL eye/dose (low dose) after approval by SRC.
If drug-related dose-limiting toxicity (DLT) events are observed in > 2 of the 6 evaluable subjects within 6 weeks after the dosing of NR082 at the high dose, the dose can be de-escalated to 3.0E9 vg, 0.05 mL eye/dose (intermediate dose) after the approval by SRC.
Injection needleDevice
Also called Syringe
19G 1 1/2IN TW filter needle with filter element (BD 305200)，used to NR082 Intraocular injection solution dose preparation; 30G 1/2IN injection needle (BD 305106)，used to NR082 Intraocular injection solution administration;
1 ml screw top syringe (BD 309628),used to NR082 Intraocular injection solution dose preparation and administration.
| Study group | Role | What they receive |
|---|---|---|
| NR082 injection | Experimental | Potential doses at the dose-finding stage:
* 0.5E9 vg, 0.05 mL/eye/dose (low dose)
* 1.5E9 vg, 0.05 mL/eye/dose (starting dose)
* 3.0E9 vg, 0.05 mL/eye/dose (intermediate dose)
* 4.5E9 vg, 0.05 mL/eye/dose (high dose) Receives: Drug: NR082 Injection; Device: Injection needle |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events (AEs)
Incidence of adverse events (AEs) within 52 weeks of NR082 intravitreal injection at different doses
Measured: 52 weeks
Incidence of serious adverse events (SAEs)
Incidence of serious adverse events (SAEs)within 52 weeks of NR082 intravitreal injection at different doses
Measured: 52 weeks
Incidence of dose-limiting toxicities (DLT)
Incidence of dose-limiting toxicities (DLT) (ocular and non-ocular) within 52 weeks of NR082 intravitreal injection at different doses
Measured: 52 weeks
Secondary outcomes (18)
Proportion (percent) of subjects with an improvement of ≥ 0.3 LogMAR from baseline in Best corrected visual acuity(BCVA) in the study eye
ETDRS visual acuity charts will used to assess proportion (percent) of subjects with an improvement of ≥ 0.3 LogMAR from baseline in Best corrected visual acuity(BCVA)
Measured: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260
Mean change from baseline in BCVA (LogMAR) in the study eye
ETDRS visual acuity charts will used to assess mean change from baseline in BCVA (LogMAR)
Measured: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260
Mean change in BCVA (LogMAR) compared to nadir*
ETDRS visual acuity charts will used to assess mean change in BCVA (LogMAR) compared to nadir
Measured: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260
Change from baseline in thepattern standard deviation (PSD)in the study eye
Visual field parameters will evaluate alterations in function of different region the retina. The HVF analyzer is used to perform standard automated perimetry, and the kinetic visual field is measured by the Humphrey static visual field automatically detected by the computer, including the foveal and macular thresholds, as well as the central field. Change from baseline in thepattern standard deviation (PSD)in the study eye.
Measured: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260
Change from baseline in the visual field index (VFI) in the study eye
Visual field parameters will evaluate alterations in function of different region the retina. The HVF analyzer is used to perform standard automated perimetry, and the kinetic visual field is measured by the Humphrey static visual field automatically detected by the computer, including the foveal and macular thresholds, as well as the central field. Change from baseline in the visual field index (VFI) in the study eye.
Measured: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260
Change from baseline in the mean deviation (MD) in the study eye
Visual field parameters will evaluate alterations in function of different region the retina. The HVF analyzer is used to perform standard automated perimetry, and the kinetic visual field is measured by the Humphrey static visual field automatically detected by the computer, including the foveal and macular thresholds, as well as the central field. Change from baseline in the mean deviation (MD) in the study eye.
Measured: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260
Change from baseline in spatial frequency parameters of contrast sensitivity in the study eye
The contrast sensitivity examination measures the subject's ability to discern targets presented at varying spatial frequencies or sizes under different contrast levels. The contrast sensitivity examination measures the full range of visual sensitivity, including brightness and contrast, and it may be used as a comprehensive assessment of visual function
Measured: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260
Change from baseline in visual evoked potential (VEP) parameters in the study eye
VEP is a visual electrophysiological examination used to identify possible ischemic optic neuropathy,including the P100 Latency,P100 Amplitude,P2 Latency,P2 Amplitude.
Measured: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260
To evaluate immunogenicity
A central laboratory will be used to evaluate anti-AAV2 neutralizing antibodies in the serum samples of all subjects.These samples will be tested by the sponsor or its designee to detect anti-AAV2 neutralizing antibodies in the samples and report the titer of confirmed positive samples. Samples confirmed positive for anti-AAV2 neutralizing antibodies will also be evaluated for the presence of neutralizing antibodies.
Measured: At Weeks 1, 2, and 6
To evaluate immunogenicity
The interferon gamma enzyme-linked immunospot (ELISpot) assay will be performed to measure the proliferative response of lymphocytes to AAV2 antigen and ND4 peptide.The number of activated cells in the sample was calculated.
Measured: At Weeks 1, 2, 6, 12, 26, 40, and 52
To evaluate vector shedding
Assessment of vector DNA shedding in tears (both eyes).Samples were analyzed to determine the presence of viral DNA in tears .
Measured: At Weeks 1, 2, 6, 12, 26, 40, and 52
To evaluate biodistribution
Assessment of biodistribution in whole blood.Samples were analyzed to determine the presence of viral DNA in whole blood.
Measured: At Weeks 1, 2, 6, 12, 26, 40, and 52
To evaluate the improvement in BCVA of the study eye (< 0.3 LogMAR)
ETDRS visual acuity charts will used to assess proportion (percent) of subjects with an improvement of ≥ 0.2 LogMAR and ≥ 0.1 LogMAR from baseline in BCVA Proportion (percent) of subjects with visual acuity of > 1.0 LogMAR before and after treatment
Measured: At Weeks 52, 78, 104, 156, 208, and 260
To evaluate the change from baseline in VFQ-25
VFQ-25 is a 25-item short form version of the 51-item National Eye Institute Visual Function Questionnaire (NEI VFQ), which can effectively measure patient-reported outcomes (including quality of life, QoL).It consists of 25 items from 12 dimensions. The total score and the score of each dimension are the mean values of non-missing items of corresponding dimensions or items, with the score range from 0 to 100 , higher scores mean a worse outcome.
Measured: At Weeks 2, 26, 52, 104, 156, 208, and 260
To evaluate the change from baseline in quality of SF-36
The SF-36 questionnaire is a universal tool for evaluating patient-reported QoL outcome. SF-36 comprises 36 questions which cover eight domains of health: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. The scale score of each domain will be calculated based on the total score of the items included in the said domain and re-adjusted to 0-100,higher scores mean a worse outcome.
Measured: At Weeks 2, 26, 52, 104, 156, 208, and 260
Change from baseline in retinal nerve fiber layer (RNFL) thickness of the study eye
OCT is an imaging technology to investigate the ocular fundus by using of the basic principle of low-coherence light interferometry. It detects the reflection or diffusion signals of biological tissue layers of different depths by inputting low-coherence light and obtains the images and quantitative results of the microscopic structure of the retina
Measured: At Weeks 2, 6,12, 26, 52, 104, 156, 208, and 260
Change from baseline in retinal ganglion cell complex thickness of the study eye
OCT is an imaging technology to investigate the ocular fundus by using of the basic principle of low-coherence light interferometry. It detects the reflection or diffusion signals of biological tissue layers of different depths by inputting low-coherence light and obtains the images and quantitative results of the microscopic structure of the retina
Measured: At Weeks 2, 6,12, 26, 52, 104, 156, 208, and 260
To evaluate the visual function improvement after NR082 treatment
Early Treatment Diabetic Retinopathy Study(ETDRS) visual acuity charts will used to assess proportion (percent) of subjects with an improvement of ≥ 0.3 LogMAR from baseline in Best corrected visual acuity(BCVA) of the non-study eye
Measured: At Weeks 2, 6,12, 26, 52, 104, 156, 208, and 260
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2022
- Study start22 May 2023
- Primary completionJul 2025 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leber Hereditary Optic Neuropathy (LHON)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- 0.5E9 vg, 0.05 mL/eye/dose (low dose) 1.5E9 vg, 0.05 mL/eye/dose (starting dose) 3.0E9 vg, 0.05 mL/eye/dose (intermediate dose) 4.5E9 vg, 0.05 mL/eye/dose (high dose)
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neurophth Therapeutics Inc
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05293626
- Sponsor's protocol ID
- NFS-01-US101
- Status last verified
- Sep 2024
- First submitted
- 9 Dec 2021
- Last updated
- 4 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Single-Arm, Open-Label, Dose-Finding Clinical Trial to Evaluate the Safety and Efficacy of Gene Therapy for Leber's Hereditary Optic Neuropathy (LHON) Associated With ND4 Mutation
- ClinicalTrials.gov ID
- NCT05293626
- Acronym / sponsor ID
- NFS-01-US101
- Conditions
- Leber Hereditary Optic Neuropathy (LHON)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Neurophth Therapeutics IncUniversity, hospital or other
- Study start
- 22 May 2023 (actual)
- Primary completion
- Jul 2025 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 24 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this clinical study is to evaluate the safety and efficacy of NR082 in the treatment of LHON caused by mitochondrial ND4 gene mutation. This study will enroll subjects aged ≥ 18 years old and ≤ 75 years old to receive a single unilateral intravitreal (IVT) injection of NR082 to evaluate its safety and efficacy. The clinical manifestations of all subjects are to be reduced visual acuity caused by LHON associated with ND4 mutation, with laboratory test showing G11778A mutation (a CLIA-certified laboratory) and reduced visual acuity lasted for > 6 months and < 10 years.
Detailed description
At the dose-finding stage, the principle is that the Safety Review Committee (SRC) will decide whether to make dose adjustment based on the safety data of the starting dose. The starting dose is 1.5×109 vg, 0.05 mL eye/dose.The safety of the starting dose will be reviewed by the SRC, and dose escalation or de-escalation is by recommendation of the SRC.The safety of the starting dose will first be performed in 6 evaluable subjects.
Criteria for Dose Modification:
Dose Escalation:
If drug-related dose-limiting toxicity (DLT) events are observed in ≤ 2 of the 6 evaluable subjects within 6 weeks after the dosing of NR082 at the starting dose, the dose can be escalated to 4.5×109 vg, 0.05 mL eye/dose (high dose) after the approval by SRC.
Dose De-escalation:
If drug-related dose-limiting toxicity (DLT) events are observed in > 2 of the 6 evaluable subjects within 6 weeks after the dosing of NR082 at the starting dose, the dose can be de-escalated to 0.5×109 vg, 0.05 mL eye/dose (low dose) after the approval by SRC.
If drug-related dose-limiting toxicity (DLT) events are observed in > 2 of the 6 evaluable subjects within 6 weeks after the dosing of NR082 at the high dose, the dose can be de-escalated to 3.0×109vg, 0.05 mL eye/dose (intermediate dose) after the approval by SRC.
Enrollment Sequence:
- The enrollment sequence of any dose group (6 subjects) is that the 2nd subject and the 3rd subject will be enrolled at least 7 days after the enrollment of the 1st subject;
- The 4th, 5th and 6th subjects will be enrolled at least 7 days after the enrollment of the 2nd and the 3rd subjects.
The 7-day interval is to avoid acute safety events to the greatest possible extent
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 0.5E9 vg, 0.05 mL/eye/dose (low dose) 1.5E9 vg, 0.05 mL/eye/dose (starting dose) 3.0E9 vg, 0.05 mL/eye/dose (intermediate dose) 4.5E9 vg, 0.05 mL/eye/dose (high dose)
| Arm | Type | Receives |
|---|---|---|
| NR082 injection | Experimental | Drug: NR082 Injection, Device: Injection needlePotential doses at the dose-finding stage: * 0.5E9 vg, 0.05 mL/eye/dose (low dose) * 1.5E9 vg, 0.05 mL/eye/dose (starting dose) * 3.0E9 vg, 0.05 mL/eye/dose (intermediate dose) * 4.5E9 vg, 0.05 mL/eye/dose (high dose) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age at the time of signing the informed consent form: the age of the subjects must be ≥ 18 years old and ≤ 75 years old.
- The clinical manifested vision loss due to LHON, and any eye BCVA ≥ 0.5 LogMAR
- The genotype testing result shows the presence of G11778A mutation in the ND4 gene, and the absence of the other primary LHON associated mutations in the mitochondrial DNA (mtDNA) (ND1 [G3460A] or ND6 [T14484C]) (confirmed by a CLIA-certified international laboratory
- The vision loss in the eye with worse visual acuity lasted > 6 months and < 10 years at screening
- Pupils can be adequately dilated for a thorough ocular examination and visual acuity test
Key exclusion criteria (22 listed)
- 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
- Narrow anterior chamber angle in any eye contra-indicating pupillary dilation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NR082 InjectionThe starting dose is 1.5E9 vg, 0.05 mL eye/dose. Dose Escalation: If drug-related dose-limiting toxicity (DLT) events are observed in ≤ 2 of the 6 evaluable subjects using the starting dose within 6 weeks after the dosing of NR082, the dose can be escalated to 4.5E9 vg, 0.05 mL eye/dose (high dose) after approval by SRC. Dose De-escalation： If drug-related dose-limiting toxicity (DLT) events are observed in > 2 of the 6 evaluable subjects using the starting dose within 6 weeks after the dosing of NR082, the dose can be de-escalated to 0.5E9 vg, 0.05 mL eye/dose (low dose) after approval by SRC. If drug-related dose-limiting toxicity (DLT) events are observed in > 2 of the 6 evaluable subjects within 6 weeks after the dosing of NR082 at the high dose, the dose can be de-escalated to 3.0E9 vg, 0.05 mL eye/dose (intermediate dose) after the approval by SRC. | Drug | NR082 injection |
| Injection needleAlso: Syringe19G 1 1/2IN TW filter needle with filter element (BD 305200)，used to NR082 Intraocular injection solution dose preparation; 30G 1/2IN injection needle (BD 305106)，used to NR082 Intraocular injection solution administration; 1 ml screw top syringe (BD 309628),used to NR082 Intraocular injection solution dose preparation and administration. | Device | NR082 injection |
Primary outcome
Incidence of adverse events (AEs)
Time frame: 52 weeks
Incidence of adverse events (AEs) within 52 weeks of NR082 intravitreal injection at different doses
Incidence of serious adverse events (SAEs)
Time frame: 52 weeks
Incidence of serious adverse events (SAEs)within 52 weeks of NR082 intravitreal injection at different doses
Incidence of dose-limiting toxicities (DLT)
Time frame: 52 weeks
Incidence of dose-limiting toxicities (DLT) (ocular and non-ocular) within 52 weeks of NR082 intravitreal injection at different doses
18 secondary outcomes
Proportion (percent) of subjects with an improvement of ≥ 0.3 LogMAR from baseline in Best corrected visual acuity(BCVA) in the study eye
Time frame: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260
Mean change from baseline in BCVA (LogMAR) in the study eye
Time frame: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260
Mean change in BCVA (LogMAR) compared to nadir*
Time frame: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260
Change from baseline in thepattern standard deviation (PSD)in the study eye
Time frame: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260
Change from baseline in the visual field index (VFI) in the study eye
Time frame: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260
Change from baseline in the mean deviation (MD) in the study eye
Time frame: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260
Change from baseline in spatial frequency parameters of contrast sensitivity in the study eye
Time frame: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260
Change from baseline in visual evoked potential (VEP) parameters in the study eye
Time frame: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 156, 208, and 260
To evaluate immunogenicity
Time frame: At Weeks 1, 2, and 6
To evaluate immunogenicity
Time frame: At Weeks 1, 2, 6, 12, 26, 40, and 52
To evaluate vector shedding
Time frame: At Weeks 1, 2, 6, 12, 26, 40, and 52
To evaluate biodistribution
Time frame: At Weeks 1, 2, 6, 12, 26, 40, and 52
To evaluate the improvement in BCVA of the study eye (< 0.3 LogMAR)
Time frame: At Weeks 52, 78, 104, 156, 208, and 260
To evaluate the change from baseline in VFQ-25
Time frame: At Weeks 2, 26, 52, 104, 156, 208, and 260
To evaluate the change from baseline in quality of SF-36
Time frame: At Weeks 2, 26, 52, 104, 156, 208, and 260
Change from baseline in retinal nerve fiber layer (RNFL) thickness of the study eye
Time frame: At Weeks 2, 6,12, 26, 52, 104, 156, 208, and 260
Change from baseline in retinal ganglion cell complex thickness of the study eye
Time frame: At Weeks 2, 6,12, 26, 52, 104, 156, 208, and 260
To evaluate the visual function improvement after NR082 treatment
Time frame: At Weeks 2, 6,12, 26, 52, 104, 156, 208, and 260
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2024.
- Individual participant dataSharing planned: No
Related trials for Leber Hereditary Optic Neuropathy (LHON)
Not yet recruitingPhase 1/2
A Basket Clinical Study to Assess Glycerol Tributyrate in Patients With Mitochondrial Encephalopathy, Lactic Acidosis, Stroke-like Episodes (MELAS) or Leber's Hereditary Optic Neuropathy-Plus (LHON-Plus)
MELAS Syndrome, Lebers Hereditory Optic Neuropathy With Extra Ocular Symptoms (LHON-Plus)
Recruiting
New Non-invasive Modalities for Assessing Retinal Structure and Function
Ischemic Optic Neuropathy, Branch Retinal Artery Occlusion
Recruiting
Stem Cell Ophthalmology Treatment Study II
Retinal Disease, Age-Related Macular Degeneration
RecruitingPhase 2
Efficacy and Safety Study of Bilateral IVT Injection of GS010 at Two Dose Levels in LHON Patients
Leber Hereditary Optic Disease
Active, not recruitingPhase 3
A Phase 3, Multicenter, Randomized, Double-Masked, Sham-Controlled Clinical Trial for Leber's Hereditary Optic Neuropathy (LHON) Associated With ND4 Mutation
Leber Hereditary Optic Neuropathy (LHON)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing NR082 Injection and Injection needle in people with Leber Hereditary Optic Neuropathy (LHON), run by Neurophth Therapeutics Inc at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (AEs) (time frame: 52 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2024.