Leber Hereditary Optic Neuropathy (LHON)Phase 1/2NCT05820152
Gene Therapy Clinical Trial for the Treatment of Leber's Hereditary Optic Neuropathy Associated With ND1 Mutations
A Phase 1/2 study testing NFS-02 Injection in people with Leber Hereditary Optic Neuropathy (LHON), run by Neurophth Therapeutics Inc at 4 sites in 2 countries.
Trial summary
The objective of this clinical study is to evaluate the safety, tolerability and preliminary efficacy of NFS-02 in the treatment of LHON caused by mitochondrial ND1 gene mutation. 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?
- NFS-02 Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 15 Aug 2023to 24 Jun 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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
- Age at the time of signing the informed consent form: the age of the subjects must be ≥ 18 years old and ≤ 75 years old Type of Subject and Disease Characteristics
- The clinical manifested vision loss due to LHON, and any eye BCVA ≥ 0.5 LogMAR
- The genotype testing result shows the presence of G3460A mutation in the ND1 gene, and the absence of the other primary LHON associated mutations in the mitochondrial DNA (mtDNA) (ND4 [G11778A] 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
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- Each eye of the subject must maintain at least Hand Motion visual acuity (VA) (≤ 2.3 LogMAR) as defined in the ocular/vision examination manual (operating manual for refraction and VA examinations) in this study
- Willingness to comply with the clinical study protocol and 5 years of long-term follow-up after administration Sex
- Male or female
- Male subjects:
- A male subject must agree to take contraceptive measures at least 6 months after the treatment visit, see Appendix 5 for details
- Female subjects:
- A female subject is eligible to participate if she is not pregnant (see Appendix 5), not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in Appendix 5 ii) A WOCBP who agrees to follow the contraception guidance in Appendix 5 for at least 6 months after the treatment visit Informed Consent
- Written informed consent form must be obtained from the subject or his/her parent/legal guardian before any study-related procedures is performed (see Section 10.2)
- 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
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- 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) (Polman C H et al., 2011), 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 clinical-related ocular surgery (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 NFS-02 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 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
4 sites in 2 countries.
4 sites in 2 countries
China3 sites
The First Medical Center of the General Hospital of the Chinese People's Liberation Army
Beijing, Beijing Municipality
Zhongshan Ophthalmic Center, Sun Yat-sen University
Guangzhou, Guangdong
Optometry Affiliated to Wenzhou Medical University
Wenzhou, Zhejiang
United States1 site
University of Colorado- Dept of Ophthalmology
Aurora, Colorado, 80045
About this study
Official title: A Phase 1/2, Multi-regional, Single-Arm, Open-Label, Dose-Finding Clinical Trial to Evaluate the Safety, Tolerability and Efficacy of Gene Therapy for Leber's Hereditary Optic Neuropathy (LHON) Associated With ND1 Mutation
The objective of this clinical study is to evaluate the safety, tolerability and preliminary efficacy of NFS-02 in the treatment of LHON caused by mitochondrial ND1 gene mutation. This study will enroll subjects aged ≥ 18 years old and ≤ 75 years old to receive a single unilateral intravitreal (IVT) injection of NFS-02 to evaluate its safety, tolerability and preliminary efficacy. The clinical manifestations of all subjects are to be reduced visual acuity caused by LHON associated with ND1 mutation, with laboratory test showing G3460A 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 1.5×108 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 NFS-02 at the starting dose, the dose can be escalated to 5.0×108 vg, 0.05 mL eye/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 NFS-02 at the 5.0×108 vg, 0.05 mL eye/dose, the dose can be escalated to 1.5×109 vg, 0.05 mL eye/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 NFS-02 at the starting dose, the dose can be de-escalated to 5.0×107 vg, 0.05 mL eye/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
- NFS-02 Injection
- 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.
NFS-02 InjectionDrug
The starting dose is 1.5×108 vg, 0.05 mL eye/dose. If drug-related dose-limiting toxicity (DLT) events are observed in < 2 of the 6 evaluable subjects within 6 weeks after the dosing of NFS-02 at the starting dose, the dose can be escalated to 5.0×108 vg, 0.05 mL eye/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 NFS-02 at the 5.0×108 vg, 0.05 mL eye/dose, the dose can be escalated to 1.5×109 vg, 0.05 mL eye/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 NFS-02 at the starting dose, the dose can be de-escalated to 5.0×107 vg, 0.05 mL eye/dose after the approval by SRC.
| Study group | Role | What they receive |
|---|---|---|
| NFS-02 Injection | Experimental | Potential doses at the dose-finding stage:
5.0×107 vg, 0.05 mL/eye/dose (low dose) 1.5×108 vg, 0.05 mL/eye/dose (starting dose) 5.0×108 vg, 0.05 mL/eye/dose (intermediate dose) 1.5×109 vg, 0.05 mL/eye/dose (high dose) Receives: Drug: NFS-02 Injection |
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 NFS-02 intravitreal injection at different doses
Measured: 52 weeks
Incidence of serious adverse events (SAEs)
Incidence of serious adverse events (SAEs)within 52 weeks of NFS-02 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 NFS-02 intravitreal injection at different doses
Measured: 52 weeks
Secondary outcomes (16)
Proportion (%) of subjects with an improvement of ≥ 0.3 LogMAR from baseline in BCVA in the injected eye and non-injected 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, 130, 156, 182, 208, 234, and 260
Mean change from baseline in BCVA (LogMAR) in the injected eye and non-injected 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, 130, 156, 182, 208, 234, and 260
Mean change in BCVA (LogMAR) compared to nadir in the injected eye and non-injected eye
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, 130, 156, 182, 208, 234, and 260
Change from baseline in the parameter of microperimetry in the injected eye and non-injected eye
Microperimetry parameters will evaluate alterations in function of different region the retina. The major parameter to be documented is mean sensitivity
Measured: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 130, 156, 182, 208, 234, and 260
Proportion (%) of subjects with a clinically meaningful improvement of injected eye from baseline in microperimetry in the injected eye and non-injected eye
Microperimetry parameters will evaluate alterations in function of different region the retina. The major parameter to be documented is mean sensitivity. A clinically meaningful improvement is defined as an improvement of 7 decibels (dB) or more post-treatment from a baseline in a pre-defined area consisting of 5 or more points in central 20° vision on microperimetry (a pre-defined area is set as central 36 loci among 68 loci of the whole grid)
Measured: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 130, 156, 182, 208, 234, and 260
Change from baseline in contrast sensitivity in the injected eye and non-injected 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, 130, 156, 182, 208, 234, and 260
Change from baseline in visual evoked potential (VEP) parameters in the injected eye and non-injected 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, 130, 156, 182, 208, 234, 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, 6, 12, 26, 40, and 52
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 ND1 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 in the injected eye and non-injected 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, 130, 156, 182, 208, 234 and 260
Change from baseline in retinal nerve fiber layer (RNFL) thickness in the injected eye and non-injected 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, 78, 104, 130, 156, 182, 208, 234 and 260
Change from baseline in retinal ganglion cell complex thickness in the injected eye and non-injected 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, 78, 104, 130, 156, 182, 208, 234 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). All items are scored so that a high score represents better functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively.
Measured: At Weeks 12, 26，52, 78, 104, 130, 156, 182, 208, 234 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 12, 26，52, 78, 104, 130, 156, 182, 208, 234 and 260
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2023
- Study start15 Aug 2023
- Primary completion24 Jun 2024
- Study completion24 Jun 2024
Why it stopped: Due to the sponsor circumstances and external reasons
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
- 5.0×107 vg, 0.05 mL eye/dose(low dose); 1.5×108 vg, 0.05 mL eye/dose(starting dose); 5.0×108 vg, 0.05 mL eye/dose(intermediate dose); 1.5×109 vg, 0.05 mL eye/dose(high dose)
- Masking
- None (open label)
- Enrolment
- 11 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
- NCT05820152
- Sponsor's protocol ID
- NFS-02-101
- Status last verified
- Sep 2024
- First submitted
- 6 Apr 2023
- Last updated
- 20 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Multi-regional, Single-Arm, Open-Label, Dose-Finding Clinical Trial to Evaluate the Safety, Tolerability and Efficacy of Gene Therapy for Leber's Hereditary Optic Neuropathy (LHON) Associated With ND1 Mutation
- ClinicalTrials.gov ID
- NCT05820152
- Acronym / sponsor ID
- NFS-02-101
- Conditions
- Leber Hereditary Optic Neuropathy (LHON)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to the sponsor circumstances and external reasons
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Neurophth Therapeutics IncUniversity, hospital or other
- Study start
- 15 Aug 2023 (actual)
- Primary completion
- 24 Jun 2024 (actual)
- Study completion
- 24 Jun 2024 (actual)
- First posted
- 19 Apr 2023 (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, tolerability and preliminary efficacy of NFS-02 in the treatment of LHON caused by mitochondrial ND1 gene mutation. This study will enroll subjects aged ≥ 18 years old and ≤ 75 years old to receive a single unilateral intravitreal (IVT) injection of NFS-02 to evaluate its safety, tolerability and preliminary efficacy. The clinical manifestations of all subjects are to be reduced visual acuity caused by LHON associated with ND1 mutation, with laboratory test showing G3460A 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 1.5×108 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 NFS-02 at the starting dose, the dose can be escalated to 5.0×108 vg, 0.05 mL eye/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 NFS-02 at the 5.0×108 vg, 0.05 mL eye/dose, the dose can be escalated to 1.5×109 vg, 0.05 mL eye/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 NFS-02 at the starting dose, the dose can be de-escalated to 5.0×107 vg, 0.05 mL eye/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
- 5.0×107 vg, 0.05 mL eye/dose(low dose); 1.5×108 vg, 0.05 mL eye/dose(starting dose); 5.0×108 vg, 0.05 mL eye/dose(intermediate dose); 1.5×109 vg, 0.05 mL eye/dose(high dose)
| Arm | Type | Receives |
|---|---|---|
| NFS-02 Injection | Experimental | Drug: NFS-02 InjectionPotential doses at the dose-finding stage: 5.0×107 vg, 0.05 mL/eye/dose (low dose) 1.5×108 vg, 0.05 mL/eye/dose (starting dose) 5.0×108 vg, 0.05 mL/eye/dose (intermediate dose) 1.5×109 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 (16 listed)
- Age
- Age at the time of signing the informed consent form: the age of the subjects must be ≥ 18 years old and ≤ 75 years old Type of Subject and Disease Characteristics
- The clinical manifested vision loss due to LHON, and any eye BCVA ≥ 0.5 LogMAR
- The genotype testing result shows the presence of G3460A mutation in the ND1 gene, and the absence of the other primary LHON associated mutations in the mitochondrial DNA (mtDNA) (ND4 [G11778A] 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
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 |
|---|---|---|
| NFS-02 InjectionThe starting dose is 1.5×108 vg, 0.05 mL eye/dose. If drug-related dose-limiting toxicity (DLT) events are observed in < 2 of the 6 evaluable subjects within 6 weeks after the dosing of NFS-02 at the starting dose, the dose can be escalated to 5.0×108 vg, 0.05 mL eye/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 NFS-02 at the 5.0×108 vg, 0.05 mL eye/dose, the dose can be escalated to 1.5×109 vg, 0.05 mL eye/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 NFS-02 at the starting dose, the dose can be de-escalated to 5.0×107 vg, 0.05 mL eye/dose after the approval by SRC. | Drug | NFS-02 Injection |
Primary outcome
Incidence of adverse events (AEs)
Time frame: 52 weeks
Incidence of adverse events (AEs) within 52 weeks of NFS-02 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 NFS-02 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 NFS-02 intravitreal injection at different doses
16 secondary outcomes
Proportion (%) of subjects with an improvement of ≥ 0.3 LogMAR from baseline in BCVA in the injected eye and non-injected eye
Time frame: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 130, 156, 182, 208, 234, and 260
Mean change from baseline in BCVA (LogMAR) in the injected eye and non-injected eye
Time frame: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 130, 156, 182, 208, 234, and 260
Mean change in BCVA (LogMAR) compared to nadir in the injected eye and non-injected eye
Time frame: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 130, 156, 182, 208, 234, and 260
Change from baseline in the parameter of microperimetry in the injected eye and non-injected eye
Time frame: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 130, 156, 182, 208, 234, and 260
Proportion (%) of subjects with a clinically meaningful improvement of injected eye from baseline in microperimetry in the injected eye and non-injected eye
Time frame: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 130, 156, 182, 208, 234, and 260
Change from baseline in contrast sensitivity in the injected eye and non-injected eye
Time frame: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 130, 156, 182, 208, 234, and 260
Change from baseline in visual evoked potential (VEP) parameters in the injected eye and non-injected eye
Time frame: At Weeks 2, 6,12, 26, 40, 52, 78, 104, 130, 156, 182, 208, 234, and 260
To evaluate immunogenicity
Time frame: At Weeks 1, 2, 6, 12, 26, 40, and 52
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 in the injected eye and non-injected eye (< 0.3 LogMAR)
Time frame: At Weeks 52, 78, 104, 130, 156, 182, 208, 234 and 260
Change from baseline in retinal nerve fiber layer (RNFL) thickness in the injected eye and non-injected eye
Time frame: At Weeks 2, 6,12, 26, 52, 78, 104, 130, 156, 182, 208, 234 and 260
Change from baseline in retinal ganglion cell complex thickness in the injected eye and non-injected eye
Time frame: At Weeks 2, 6,12, 26, 52, 78, 104, 130, 156, 182, 208, 234 and 260
To evaluate the change from baseline in VFQ-25
Time frame: At Weeks 12, 26，52, 78, 104, 130, 156, 182, 208, 234 and 260
To evaluate the change from baseline in quality of SF-36
Time frame: At Weeks 12, 26，52, 78, 104, 130, 156, 182, 208, 234 and 260
Results and safety
The study was stopped early (reason given: Due to the sponsor circumstances and external reasons). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2024.
- Individual participant dataSharing planned: No
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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.
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing NFS-02 Injection in people with Leber Hereditary Optic Neuropathy (LHON), run by Neurophth Therapeutics Inc at 4 sites in 2 countries.
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 16 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: stopped early, as of the sponsor's last update on 20 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 4 sites in China, 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?
The study was stopped early (reason given: Due to the sponsor circumstances and external reasons). Results are not available in the source record.
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 20 Sep 2024.