Autosomal Dominant Optic AtrophyNCT06140329
Natural History of Autosomal Dominant Optic Atrophy (ADOA), Caused by OPA1 Mutation
An observational study of Autosomal Dominant Optic Atrophy and Optic Atrophy, Autosomal Dominant, run by PYC Therapeutics at 7 sites in 6 countries.
Trial summary
The purpose of this study is to characterize the disease progression of confirmed OPA1 mutation-associated autosomal dominant optic atrophy (ADOA) by evaluating the changes in ocular structural and functional outcomes. Read more about this study
- Who is it for?
- Ages 8 years and older
- Conditions the study is for
- Autosomal Dominant Optic Atrophy, Optic Atrophy, Autosomal Dominant, Optic Atrophies, Hereditary
- How many people
- 1 participants
- Where
- 7 sitesin 6 countries
- Study dates
- 28 Feb 2024to 10 Mar 2025
- Phase
- Observational
- 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 8 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: The study population will consist of approximately 40 participants (80 eyes) with a genetically confirmed OPA1 mutation.
Who may be able to join
- Participants and/or their parent(s)/guardian(s) must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects. Assent, where appropriate, will be obtained according to institutional guidelines.
- Males and females, 8 years of age and above.
- Have a clinical diagnosis of OPA1 mutation (haploinsufficiency) associated ADOA.
- No other ocular pathology.
- Patients with best-corrected visual acuity (BCVA) of between 20/40 (70 Early Treatment of Diabetic Retinopathy Study [ETDRS] letters) and 20/160 (39-43 ETDRS letters)
- Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
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- For sites performing the Detection of apoptosis in retinal cells (DARC) procedure, and in volunteers ≥ 12 years only:
- Female volunteers must:
- Be of non-child-bearing potential at least 6 weeks before the screening visit or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause), or
- If of childbearing potential, must:
- Have a negative pregnancy test at the screening visit and prior to each administration of ANX776, and
- Agree not to attempt to become pregnant or donate ova from signing the consent form until at least 30 days after the last dose of ANX776, and
- Agree to use adequate contraception (defined as the use of a condom by the male partner combined with the use of a highly effective method of contraception from one month prior to screening until at least 30 days after the last dose of ANX776, if not exclusively in a same-sex relationship or abstinent as a committed lifestyle.
- Male volunteers must:
- Agree not to donate sperm from signing the consent form until at least 90 days after the last dose of ANX776, and
- If engaging in sexual intercourse with a female partner who could become pregnant, agree to use adequate contraception (defined as the use of a condom combined with the use of a highly effective method of contraception) from signing the consent form until at least 90 days after the last dose of study drug.
Who cannot join
- Participant has a known allergy to ANX776 or any of its excipients.
- Have any uncontrolled systemic disease that, in the opinion of the Investigator, would preclude participation in the study, which includes but is not limited to, infection, uncontrolled elevated blood pressure, cardiovascular disease, or glycemic control issues, or any other medical condition that may put the participant at risk due to study procedures. Note: comorbidities relevant to the pathogenesis of OPA1 associated ADOA (including hearing loss, peripheral neuropathy, myopathy, and ataxia) are acceptable.
- Have mutations in genes that cause ADOA, other than OPA1 (for example in case of dominant negative ADOA) and ADOA Plus.
- Within 3 months prior to Baseline (Visit 2), have undergone any vitreoretinal surgery (scleral buckle, pars plana vitrectomy, retrieval of a dropped nucleus or intraocular lens, radial optic neurotomy, sheathotomy, cyclodestructive procedures or multiple filtration surgeries [2 or more]) or any other ocular surgery.
- Have ocular media opacity or poor pupillary dilation prohibiting quality ophthalmic evaluation or photography, as assessed by the Investigator.
- Have used any investigational drug or device within 90 days or 5 estimated half-lives of Visit 2, whichever is longer, or plan to participate in another study of a drug or device during the study period. Participation in observational trials is allowable based on Investigator discretion and consultation with the Medical Monitor. It is assumed that the observational trial evaluations would not interfere with participation in this study.
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- Have received any prior cell or gene therapy for a retinal condition.
- Have a recent history (<6 months) of or current excessive recreational drug or alcohol use, in the opinion of the Investigator. Note: excessive alcohol use is defined as regular consumption of > 10 standard drinks per week or > 4 standard drinks per day, where 1 standard drink is defined as 10 grams of pure alcohol.
- Any other condition or prior therapy that in the opinion of the Investigator would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.
Trial locations and contacts
7 sites in 6 countries.
7 sites in 6 countries
United States2 sites
Bascom Palmer Eye Institute
Miami, Florida, 33136
University of Washington
Seattle, Washington, 98104
About this study
Official title: A Natural History Study in Patients With Genetically Confirmed Diagnosis of Autosomal Dominant Optic Atrophy (ADOA), Caused by OPA1 Mutation
The purpose of this study is to characterize the disease progression of confirmed OPA1 mutation-associated autosomal dominant optic atrophy (ADOA) by evaluating the changes in ocular structural and functional outcomes.
Read the detailed description
This is a multi-center, longitudinal, prospective, observational natural history study of patients with confirmed OPA1 mutation (haploinsufficiency) associated ADOA. The study will be conducted at up to 10 sites across the United States, Australia and Europe.
Each participant's medical record will be reviewed for historical information, and clinical data will be recorded in a secure database. Natural history data will be collected prospectively and will include ophthalmic exams, imaging studies and electrophysiological testing. Assessments will be conducted as described in this protocol approximately every 3 months in the first year and every 6 months in the second year of the study after each participant's baseline visit
- Conditions
- Autosomal Dominant Optic Atrophy, Optic Atrophy, Autosomal Dominant, Optic Atrophies, Hereditary, Kjer Optic Atrophy
- Medical subject headings
- Optic Atrophy, Autosomal Dominant, Optic Atrophies, Hereditary
What is being measured
The primary outcome is the main question the study is designed to answer.
Best-corrected High Contrast Visual Acuity (HCVA)
Best-corrected high contrast visual acuity (HCVA) for both distance and near will be evaluated using the ETDRS electronic visual acuity charts and the MNRead acuity chart
Measured: Baseline through Year 2
Low Contrast Visual Acuity (LCVA)
Low contrast visual acuity (LCVA) for both distance and near will be evaluated using the low contrast ETDRS letter chart
Measured: Screening through Year 2
Contrast Sensitivity
Contrast sensitivity recorded using the Pelli-Robson chart
Measured: Baseline through Year 2
Color Vision
Color vision tested using the Hardy Rand Rittler test
Measured: Baseline through Year 2
Retinal Thickness
Change retinal thickness is measured using spectral domain optical coherence tomography (SD-OCT), as measured by the central reading center (SD-OCT), as measured by the central reading center
Measured: Baseline through Year 2
Ellipsoid Zone (EZ) Volume
Change in EZ volume measured using spectral domain optical coherence tomography (SD-OCT), as measured by the central reading center
Measured: Baseline through Year 2
Ellipsoid Zone (EZ) Area
Change in EZ area measured using spectral domain optical coherence tomography (SD-OCT), as measured by the central reading center
Measured: Baseline through Year 2
Visual Field Sensitivity
Visual field sensitivity measured by automated static perimetry
Measured: Baseline through Year 2
Multifocal Visual Evoked Potential (mfVEP)
The waveform of the evoked responses, the latency, and amplitude are analyzed.
Measured: Baseline through Year 2
Pregnancy Test
A urine human chorionic gonadotropin (hCG) pregnancy conducted in all women of childbearing potential (WOCBP) > 12 years of age at baseline. If a urine test is positive, the DARC procedure will not be performed.
Measured: Baseline
DARC (Detection of Apoptosing Retinal Cells)
The DARC test is conducted using an IV injection of fluorescently labelled Annexin V (called ANX776). Individual stressed and apoptotic retinal cells are visible as white spots on the image for DARC count, which are quantified using a confocal scanning laser ophthalmoscope using the indocyanine green angiography (ICGA) settings.
Measured: Baseline through Year 2
Flavoprotein Fluorescence (FPF)
Functional imaging of mitochondria using Flavoprotein Fluorescence.
Measured: Baseline through Year 2
Retinal Abnormalities
Ultrawide fundus photography is conducted OU to assess retinal abnormalities
Measured: Baseline through Year 2
Adverse Events (AEs)
Frequency of ocular adverse events (AEs)
Measured: Screening through Year 2
Genomic Analysis for Study Eligibility
OPA1 genetic testing at screening visit
Measured: Screening
Vital signs
Vital signs assessments (pulse rate, body temperature, systolic and diastolic blood pressure, and respiratory rate) performed in participants undergoing the DARC assessment only.
Measured: Baseline through Year 2
Secondary outcomes (1)
To determine the outcome measures that are associated with ADOA disease progression.
To understand the disease progression in participants with confirmed OPA1 mutation-associated ADOA determined by changes in structural and functional markers from the primary outcome within the study period.
Measured: Baseline through Year 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2023
- Study start28 Feb 2024
- Primary completion1 Mar 2025
- Study completion10 Mar 2025
Why it stopped: The study was terminated due to low participant enrolment and to accommodate PYC's future interventional study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autosomal Dominant Optic AtrophyStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- PYC Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sreenivasu Mudumba, PhD, Study chair, PYC Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06140329
- Sponsor's protocol ID
- PYC-001
- Status last verified
- Mar 2025
- First submitted
- 15 Nov 2023
- Last updated
- 14 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Natural History Study in Patients With Genetically Confirmed Diagnosis of Autosomal Dominant Optic Atrophy (ADOA), Caused by OPA1 Mutation
- ClinicalTrials.gov ID
- NCT06140329
- Acronym / sponsor ID
- PYC-001
- Conditions
- Autosomal Dominant Optic Atrophy, Optic Atrophy, Autosomal Dominant, Optic Atrophies, Hereditary, Kjer Optic Atrophy
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: The study was terminated due to low participant enrolment and to accommodate PYC's future interventional study.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- PYC TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 28 Feb 2024 (actual)
- Primary completion
- 1 Mar 2025 (actual)
- Study completion
- 10 Mar 2025 (actual)
- First posted
- 18 Nov 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 purpose of this study is to characterize the disease progression of confirmed OPA1 mutation-associated autosomal dominant optic atrophy (ADOA) by evaluating the changes in ocular structural and functional outcomes.
Detailed description
This is a multi-center, longitudinal, prospective, observational natural history study of patients with confirmed OPA1 mutation (haploinsufficiency) associated ADOA. The study will be conducted at up to 10 sites across the United States, Australia and Europe.
Each participant's medical record will be reviewed for historical information, and clinical data will be recorded in a secure database. Natural history data will be collected prospectively and will include ophthalmic exams, imaging studies and electrophysiological testing. Assessments will be conducted as described in this protocol approximately every 3 months in the first year and every 6 months in the second year of the study after each participant's baseline visit
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 8 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study population will consist of approximately 40 participants (80 eyes) with a genetically confirmed OPA1 mutation.
Key inclusion criteria (16 listed)
- Participants and/or their parent(s)/guardian(s) must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects. Assent, where appropriate, will be obtained according to institutional guidelines.
- Males and females, 8 years of age and above.
- Have a clinical diagnosis of OPA1 mutation (haploinsufficiency) associated ADOA.
- No other ocular pathology.
- Patients with best-corrected visual acuity (BCVA) of between 20/40 (70 Early Treatment of Diabetic Retinopathy Study [ETDRS] letters) and 20/160 (39-43 ETDRS letters)
Key exclusion criteria (9 listed)
- Participant has a known allergy to ANX776 or any of its excipients.
- Have any uncontrolled systemic disease that, in the opinion of the Investigator, would preclude participation in the study, which includes but is not limited to, infection, uncontrolled elevated blood pressure, cardiovascular disease, or glycemic control issues, or any other medical condition that may put the participant at risk due to study procedures. Note: comorbidities relevant to the pathogenesis of OPA1 associated ADOA (including hearing loss, peripheral neuropathy, myopathy, and ataxia) are acceptable.
- Have mutations in genes that cause ADOA, other than OPA1 (for example in case of dominant negative ADOA) and ADOA Plus.
- Within 3 months prior to Baseline (Visit 2), have undergone any vitreoretinal surgery (scleral buckle, pars plana vitrectomy, retrieval of a dropped nucleus or intraocular lens, radial optic neurotomy, sheathotomy, cyclodestructive procedures or multiple filtration surgeries [2 or more]) or any other ocular surgery.
- Have ocular media opacity or poor pupillary dilation prohibiting quality ophthalmic evaluation or photography, as assessed by the Investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Best-corrected High Contrast Visual Acuity (HCVA)
Time frame: Baseline through Year 2
Best-corrected high contrast visual acuity (HCVA) for both distance and near will be evaluated using the ETDRS electronic visual acuity charts and the MNRead acuity chart
Low Contrast Visual Acuity (LCVA)
Time frame: Screening through Year 2
Low contrast visual acuity (LCVA) for both distance and near will be evaluated using the low contrast ETDRS letter chart
Contrast Sensitivity
Time frame: Baseline through Year 2
Contrast sensitivity recorded using the Pelli-Robson chart
Color Vision
Time frame: Baseline through Year 2
Color vision tested using the Hardy Rand Rittler test
Retinal Thickness
Time frame: Baseline through Year 2
Change retinal thickness is measured using spectral domain optical coherence tomography (SD-OCT), as measured by the central reading center (SD-OCT), as measured by the central reading center
Ellipsoid Zone (EZ) Volume
Time frame: Baseline through Year 2
Change in EZ volume measured using spectral domain optical coherence tomography (SD-OCT), as measured by the central reading center
Ellipsoid Zone (EZ) Area
Time frame: Baseline through Year 2
Change in EZ area measured using spectral domain optical coherence tomography (SD-OCT), as measured by the central reading center
Visual Field Sensitivity
Time frame: Baseline through Year 2
Visual field sensitivity measured by automated static perimetry
Multifocal Visual Evoked Potential (mfVEP)
Time frame: Baseline through Year 2
The waveform of the evoked responses, the latency, and amplitude are analyzed.
Pregnancy Test
Time frame: Baseline
A urine human chorionic gonadotropin (hCG) pregnancy conducted in all women of childbearing potential (WOCBP) > 12 years of age at baseline. If a urine test is positive, the DARC procedure will not be performed.
DARC (Detection of Apoptosing Retinal Cells)
Time frame: Baseline through Year 2
The DARC test is conducted using an IV injection of fluorescently labelled Annexin V (called ANX776). Individual stressed and apoptotic retinal cells are visible as white spots on the image for DARC count, which are quantified using a confocal scanning laser ophthalmoscope using the indocyanine green angiography (ICGA) settings.
Flavoprotein Fluorescence (FPF)
Time frame: Baseline through Year 2
Functional imaging of mitochondria using Flavoprotein Fluorescence.
Retinal Abnormalities
Time frame: Baseline through Year 2
Ultrawide fundus photography is conducted OU to assess retinal abnormalities
Adverse Events (AEs)
Time frame: Screening through Year 2
Frequency of ocular adverse events (AEs)
Genomic Analysis for Study Eligibility
Time frame: Screening
OPA1 genetic testing at screening visit
Vital signs
Time frame: Baseline through Year 2
Vital signs assessments (pulse rate, body temperature, systolic and diastolic blood pressure, and respiratory rate) performed in participants undergoing the DARC assessment only.
1 secondary outcome
To determine the outcome measures that are associated with ADOA disease progression.
Time frame: Baseline through Year 2
Results and safety
The study was stopped early (reason given: The study was terminated due to low participant enrolment and to accommodate PYC's future interventional study.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2025.
- Individual participant dataSharing planned: No
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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.
Sreenivasu Mudumba, PhD study chair
PYC Therapeutics
7 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Autosomal Dominant Optic Atrophy and Optic Atrophy, Autosomal Dominant, run by PYC Therapeutics at 7 sites in 6 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 9 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 14 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Australia, Austria, France, Germany and 1 more country. 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.
Are results available for this study?
The study was stopped early (reason given: The study was terminated due to low participant enrolment and to accommodate PYC's future interventional study.). 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?
Best-corrected High Contrast Visual Acuity (HCVA) (time frame: Baseline through Year 2). The study lists 16 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 14 Mar 2025.