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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06970106




Registration number
NCT06970106
Ethics application status
Date submitted
28/04/2025
Date registered
14/05/2025

Titles & IDs
Public title
Safety of Single and Repeat Dose of PYC-001 Eye Injections in People With Autosomal Dominant Optic Atrophy
Scientific title
A Phase 1b Open-Label, Randomized, Single Dose and Repeat Dose Study to Evaluate the Single and Repeat Dose Safety and Tolerability of Intravitreally Administered PYC-001 in Participants With Confirmed OPA1 Mutation-Associated Autosomal Dominant Optic Atrophy
Secondary ID [1] 0 0
PYC-001-CL-102
Universal Trial Number (UTN)
Trial acronym
PYC-001-CL-102
Linked study record

Health condition
Health condition(s) or problem(s) studied:
OPA1 Gene Mutation 0 0
Autosomal Dominant Optic Atrophy 0 0
Hereditary Optic Atrophies 0 0
Kjer Optic Atrophy 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Eye 0 0 0 0
Diseases / disorders of the eye
Neurological 0 0 0 0
Other neurological disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Neurodegenerative diseases
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PYC-001

Experimental: Cohort 1: Single Dose of 60ug - A single dose of 60ug of PYC-001 administered intravitreally

Experimental: Cohort 2: 10ug of PYC-001, 8 weeks - 3 doses of 10ug PYC-001, administered intravitreally in 8 weeks interval

Experimental: Cohort 3: 10ug of PYC-001, 12 weeks - 3 doses of 10ug PYC-001, administered intravitreally in 12 weeks interval

Experimental: Cohort 4: 30ug of PYC-001, 8 weeks - 3 doses of 30ug PYC-001, administered intravitreally in 8 weeks interval

Experimental: Cohort 5: 30ug of PYC-001, 12 weeks - 3 doses of 30ug PYC-001, administered intravitreally in 12 weeks interval

Experimental: Cohort 6: 60ug of PYC-001, 8 weeks - Following SRC, Single dose participant can continue to receive 3 doses of 60ug PYC-001, administered intravitreally at 8 weeks interval

Experimental: Cohort 7: 60ug of PYC-001, 12 weeks - Following SRC, Single dose participant can continue to receive 3 doses of 60ug PYC-001, administered intravitreally at 12 weeks interval


Treatment: Drugs: PYC-001
PYC-001 is a peptide-phosphorodiamidate morpholino oligonucleotide administered intravitreally
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
(Cohort 1) Adverse Events
Timepoint [1] 0 0
48 weeks
Primary outcome [2] 0 0
(Cohort 1) Heart Rate change from baseline at Week 8/Week 48
Timepoint [2] 0 0
8 / 48 Weeks
Primary outcome [3] 0 0
(Cohort 1) Blood Pressure Change from baseline at Week 8/Week 48
Timepoint [3] 0 0
8 Weeks/ 48 Weeks
Primary outcome [4] 0 0
(Cohort 1) tympanic temperature change from baseline at Week 8/Week 48
Timepoint [4] 0 0
8 weeks / 48 weeks
Primary outcome [5] 0 0
(Cohort 1) Respiratory rate change from baseline at Week 8 / Week 48
Timepoint [5] 0 0
8 weeks / 48 weeks
Primary outcome [6] 0 0
(Cohort 1) Change from baseline for clinical laboratory results - hematology to Week 8 / Week 48
Timepoint [6] 0 0
8 Weeks / 48 Weeks
Primary outcome [7] 0 0
(Cohort 1) Change from baseline for clinical laboratory results - clinical chemistry to Week 8/Week 48
Timepoint [7] 0 0
8 Weeks / 48 Weeks
Primary outcome [8] 0 0
(Cohort 1) Change in coagulation - Clinical laboratory results from baseline to Week 8/Week 48
Timepoint [8] 0 0
8 Weeks / 48 Weeks
Primary outcome [9] 0 0
(Cohort 1) Change in urinalysis - Clinical laboratory results from baseline to Week 8/Week 48
Timepoint [9] 0 0
8 Weeks / 48 Weeks
Primary outcome [10] 0 0
(Repeat Dose Cohorts) Adverse Events
Timepoint [10] 0 0
48 Weeks / 60 Weeks
Primary outcome [11] 0 0
(Repeat Dose Cohorts) Heart Rate change from baseline at Week 48 / Week 60
Timepoint [11] 0 0
48 Weeks / 60 Weeks
Primary outcome [12] 0 0
(Repeat Dose Cohorts) Blood Pressure Change from baseline at Week 48/ Week 60
Timepoint [12] 0 0
48 Weeks / 60 Weeks
Primary outcome [13] 0 0
(Repeat Dose Cohorts) Tympanic Temperature Change from baseline at Week 48/ Week 60
Timepoint [13] 0 0
48 Weeks / 60 Weeks
Primary outcome [14] 0 0
(Repeat Dose Cohorts) Respiratory Rate Change from baseline at Week 48/ Week 60
Timepoint [14] 0 0
48 Weeks / 60 Weeks
Primary outcome [15] 0 0
(Repeat Dose Cohorts) Change in Clinical laboratory results - hematology from baseline at Week 48/ Week 60
Timepoint [15] 0 0
48 Weeks / 60 Weeks
Primary outcome [16] 0 0
(Repeat Dose Cohorts) Change in Clinical laboratory results - clinical chemistry from baseline at Week 48/ Week 60
Timepoint [16] 0 0
48 Weeks / 60 Weeks
Primary outcome [17] 0 0
(Repeat Dose Cohorts) Change in Clinical laboratory results - coagulation from baseline at Week 48/ Week 60
Timepoint [17] 0 0
48 Weeks / 60 Weeks
Primary outcome [18] 0 0
(Repeat Dose Cohorts) Change in Clinical laboratory results - urinalysis from baseline at Week 48/ Week 60
Timepoint [18] 0 0
48 Weeks / 60 Weeks
Secondary outcome [1] 0 0
(Cohort 1) Change from Baseline for Best-corrected visual acuity letter score using Early Treatment of Diabetic Retinopathy Study
Timepoint [1] 0 0
48 weeks
Secondary outcome [2] 0 0
(Cohort 1) Change from Baseline for Low contrast visual acuity
Timepoint [2] 0 0
48 weeks
Secondary outcome [3] 0 0
(Cohort 1) Change from Baseline for High contrast visual acuity
Timepoint [3] 0 0
48 weeks
Secondary outcome [4] 0 0
(Cohort 1) Change from Baseline for Visual field sensitivity by photopic static perimetry
Timepoint [4] 0 0
48 weeks
Secondary outcome [5] 0 0
(Cohort 1) Change from Baseline for Posterior eye health by fundus examination, using ultrawide fundoscopy
Timepoint [5] 0 0
48 weeks
Secondary outcome [6] 0 0
(Cohort 1) Change from Baseline for Color vision by Hardy Rand Rittler test
Timepoint [6] 0 0
48 weeks
Secondary outcome [7] 0 0
(Cohort 1) Change from Baseline for Contrast sensitivity by Pelli Robson chart
Timepoint [7] 0 0
48 weeks
Secondary outcome [8] 0 0
(Cohort 1) Change from Baseline for Multifocal visual evoked potential
Timepoint [8] 0 0
48 weeks
Secondary outcome [9] 0 0
(Cohort 1) Change from Baseline for Retinal nerve fiber layer (RNFL) of the eye, determined by the Spectralis Glaucoma Module Premium Edition (GMPE) RNFL & visual field structure function data
Timepoint [9] 0 0
48 weeks
Secondary outcome [10] 0 0
(Cohort 1) Change from Baseline for Mitochondrial function test by flavoprotein fluorescence analyzer (Ocumet Beacon)
Timepoint [10] 0 0
48 weeks
Secondary outcome [11] 0 0
(Repeat Dose Cohort) Change from Baseline for Best-corrected visual acuity letter score using Early Treatment of Diabetic Retinopathy Study
Timepoint [11] 0 0
48 weeks / 60 Weeks
Secondary outcome [12] 0 0
(Repeat Dose Cohort) Change from Baseline for Low contrast visual acuity
Timepoint [12] 0 0
48 weeks / 60 Weeks
Secondary outcome [13] 0 0
(Repeat Dose Cohort) Change from Baseline for High contrast visual acuity
Timepoint [13] 0 0
48 weeks / 60 Weeks
Secondary outcome [14] 0 0
(Repeat Dose Cohort) Change from Baseline for Visual field sensitivity by photopic static perimetry
Timepoint [14] 0 0
48 weeks / 60 Weeks
Secondary outcome [15] 0 0
(Repeat Dose Cohort) Change from Baseline for Posterior eye health by fundus examination, using ultrawide fundoscopy
Timepoint [15] 0 0
48 weeks / 60 Weeks
Secondary outcome [16] 0 0
(Repeat Dose Cohort) Change from Baseline for Color vision by Hardy Rand Rittler test
Timepoint [16] 0 0
48 weeks / 60 Weeks
Secondary outcome [17] 0 0
(Repeat Dose Cohort) Change from Baseline for Contrast sensitivity by Pelli Robson chart
Timepoint [17] 0 0
48 weeks / 60 Weeks
Secondary outcome [18] 0 0
(Repeat Dose Cohort) Change from Baseline for Multifocal visual evoked potential
Timepoint [18] 0 0
48 weeks / 60 Weeks
Secondary outcome [19] 0 0
(Repeat Dose Cohort) Change from Baseline for Retinal nerve fiber layer (RNFL), as determined by the Spectralis Glaucoma Module Premium Edition (GMPE)
Timepoint [19] 0 0
48 weeks / 60 Weeks
Secondary outcome [20] 0 0
(Repeat Dose Cohort) Change from Baseline for Mitochondrial function test by flavoprotein fluorescence analyzer (Ocumet Beacon)
Timepoint [20] 0 0
48 weeks / 60 Weeks
Secondary outcome [21] 0 0
(Repeat Dose Cohort) Change from Baseline for Visual field using OLLEYES mobile device
Timepoint [21] 0 0
48 weeks / 60 Weeks
Secondary outcome [22] 0 0
(Repeat Dose Cohort) Plasma concentrations of PYC-001 following multiple dose intravitreally administered PYC-001
Timepoint [22] 0 0
48 weeks / 60 Weeks
Secondary outcome [23] 0 0
(Cohort 1) Change from Baseline for Ganglion Cell Layer (GCL) thickness determined by Spectralis Glaucoma Module Premium Edition (GMPE)
Timepoint [23] 0 0
48 weeks
Secondary outcome [24] 0 0
(Cohort 1) Change from Baseline for cup/disc ratio (CDR) , as determined by Spectralis Glaucoma Module Premium Edition (GMPE)
Timepoint [24] 0 0
48 weeks
Secondary outcome [25] 0 0
(Repeat Dose Cohort) Change from Baseline for Ganglion Cell Layer (GCL) thickness determined by Spectralis Glaucoma Module Premium Edition (GMPE)
Timepoint [25] 0 0
48 weeks / 60 Weeks
Secondary outcome [26] 0 0
(Repeat Dose Cohort) Change from Baseline for cup/disc ratio (CDR) , as determined by Spectralis Glaucoma Module Premium Edition (GMPE)
Timepoint [26] 0 0
48 weeks / 60 Weeks
Secondary outcome [27] 0 0
(Repeat Dose Cohort) Change from Baseline for visual acuity using OLLEYES mobile device
Timepoint [27] 0 0
48 weeks / 60 Weeks
Secondary outcome [28] 0 0
(Repeat Dose Cohort) Change from Baseline for contrast sensitivity using OLLEYES mobile device
Timepoint [28] 0 0
48 weeks / 60 Weeks
Secondary outcome [29] 0 0
(Repeat Dose Cohort) Change from Baseline for color vision using OLLEYES mobile device
Timepoint [29] 0 0
48 weeks / 60 Weeks

Eligibility
Key inclusion criteria
1. Must give written informed consent before any study-related activity is carried out and must be able to understand the full nature and purpose of the study, including possible risks and adverse effects;
2. Adult males and females, aged 18 years and above at screening;
3. Body mass index =18.0 and =32.0 kg/m2, with a body weight =100 kg at screening;
4. Have a recent (within five years) genetic diagnosis of OPA1 mutation-associated (haploinsufficiency) ADOA and/or confirmed diagnosis during screening, as determined by the PI. In case of complex mutation profile, eligibility will be determined in consultation with the Sponsor. Rollover participants are exempt from this criterion as their genetic diagnosis was confirmed in PYC-001-101;
5. Treatment naïve participants with best-corrected visual acuity (BCVA) of between =20/40 (=70 Early Treatment of Diabetic Retinopathy Study [ETDRS] letters) and =20/200 (=35 ETDRS letters). If both eyes meet this eligibility criteria, the eye with better fixation or better vision as determined by the PI in consultation with the Sponsor will be selected as the study eye and the other eye will be designated as the fellow eye. PYC-001-101 participants are exempt from this criterion and will have the same study eye and fellow eye as determined in PYC-001-101;
6. Treatment Naïve participants (participants from PYC-001-101 are exempt from this criterion) with mild to moderate visual field loss and retinal nerve fiber layer (RNFL) loss in the study eye only as determined by the Spectralis Glaucoma Module Premium Edition (GMPE) RNFL & visual field structure function data (map), defined as:

1. Mild disease = RNFL abnormalities (outside normal range) in no more than one of six sectors;
2. Moderate disease = RNFL abnormalities (outside normal range) in no more than three of six sectors;
3. Severe disease = RNFL abnormalities (outside normal range) in four of six sectors;
4. Advanced disease = RNFL abnormalities (outside normal range) in six of six sectors;
7. Medically healthy (in the opinion of the PI), as determined by pre-study medical history, and without clinically significant abnormalities including (assessments may be repeated at the discretion of the PI if an out-of-range value is determined to be erroneous):

1. Physical examination without any clinically relevant findings;
2. Systolic blood pressure (BP) in the range of 90 to 160 mmHg and diastolic BP in the range of 50 to 95 mmHg after five minutes in sitting or supine or semi-supine position;
3. Heart rate (HR) in the range of 45 to 110 bpm after five minutes rest in sitting or supine or semi-supine position;
4. Body temperature (tympanic), between 35.5°C and 37.7°C;
5. No clinically significant findings in clinical chemistry, hematology, coagulation and urinalysis tests at screening .
8. Female participants must be of non-childbearing potential, ie, surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least six weeks before the screening visit) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle stimulating hormone [FSH] level consistent with postmenopausal status, per local laboratory guidelines). Females receiving hormone replacement therapy (HRT) may be considered for inclusion if the need for HRT is for no other medical reason than to treat symptoms associated with menopause. If female participants are of childbearing potential, they must:

1. Have a negative pregnancy test at the screening visit and on study Day -1;
2. Agree not to attempt to become pregnant or donate ova from signing of the consent form until at least 130 days after final IVT dose administration of PYC-001;
3. Agree to use adequate contraception (defined as use of a condom by the male partner combined with use of a highly effective method of contraception from one month prior to screening until at least 130 days after final IVT dose administration of PYC-001 , if not exclusively in a same-sex relationship or abstinent as a committed lifestyle.
9. Male participants must:

1. Agree not to donate sperm from signing the consent form until at least 190 days after final IVT dose administration of PYC-001;
2. If engaging in sexual intercourse with a female partner who could become pregnant, agree to use adequate contraception (defined as use of a condom combined with use of a highly effective method of contraception from signing the consent form until at least 190 days after final IVT dose administration of PYC-001;
3. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, agree to use a condom from signing the consent form until at least 190 days after final IVT dose administration of PYC-001 and;
10. Willing and able to comply
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participant has a known allergy to PYC-001 or any of its excipients;
2. Demonstrated clinically significant co-morbidities, which, in the opinion of the PI, would interfere with the participant's ability to participate in the study and/or confound study outcomes;
3. Females who are breastfeeding or planning to breastfeed;
4. Based on recent (within five years of screening [for rollover PYC-001-101 participants, within five years of entry into PYC-001-101]) genetic testing, the participant has mutations in genes that cause ADOA, other than OPA1 (for example in case of dominant negative ADOA and ADOA Plus) or has other pathological variants that result in an ADOA-like optic atrophic phenotype or other pathologic genetic findings indicating presence of additional confounding ocular diseases based on comprehensive genetic screening. Eligibility will be determined by the PI in consultation with the Sponsor as needed;
5. Have received any prior cell or gene therapy for a retinal condition, excluding participation in study PYC-001-101;
6. Within three months prior to study Day -1, 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 [two or more]) or any other ocular surgery in the study eye. This criterion does not apply for rollover participants from PYC-001-101;
7. Within three months prior to study Day -1, have placement of an Ozurdex® implant. This criterion does not apply for rollover participants from PYC-001-101;
8. Within three years prior to study Day -1, have placement of Retisert® of Iluvien® implants. This criterion does not apply for rollover participants from PYC-001-101;
9. Have ocular media opacity or poor pupillary dilation prohibiting quality ophthalmic evaluation or photography, as assessed by the PI in the study eye ;
10. Macular edema (intraretinal, sub-retinal or other fluid) in the study eye requiring treatment.
11. History of recurrent uveitis (idiopathic or immune-related) or active ocular inflammation;
12. Have used within 30 days of the Screening visit or is using any investigational drug or over-the-counter drug such as Idebenone or Vitamin B6 or a device which in the opinion of the PI or Sponsor could affect the optic nerve and/or influence functional vision or visual function during the study period. A decision will be made on a case-by-case basis by the PI in consultation with the Sponsor. Participation in observational studies is allowable based on PI discretion and consultation with the Sponsor's Medical Representative. Participation in PYC-001-101 is allowed;
13. Over-the-counter drugs like CoQ10 and other Nutraceutical usage will require a washout by five half-lives prior to baseline visit. Participants may need to stop taking the drug for the duration of the study based on Physician discretion and in consultation with the Medical Monitor;
14. Have a recent history (<6 months) of or current excessive recreational drug or alcohol use, in the opinion of the PI. Excessive alcohol use is defined as regular consumption of >10 standard drinks per week or >4 standard drinks per day, where one standard drink is defined as 10 grams of pure alcohol;
15. Positive alcohol breath test as assessed at screening, and on study Day -1 and study Day 1;
16. Positive urine drugs of abuse as assessed at screening and on study Day -1 and study Day 1;
17. Any retinal pathology other than ADOA or any other condition or prior therapy that in the opinion of the PI 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;
18. Presence of illness or pathology that, per investigator, include symptoms and/or the associated treatments that can alter visual function. For example, cancers or pathology of the central nervous system, including multiple sclerosis;
19. Positive test for human immunodeficiency virus, hepatitis B or C virus;
20. Clinically significant findings in clinical chemistry, hematology, coagulation and urinalysis tests at screening, defined as:

* Alanine transaminase (ALT) or aspartate aminotransferase (AST) >2 × upper limit of normal (ULN) or bilirubin >1.5 × ULN (unless patient has Gilbert's syndrome);
* Estimated glomerular filtration rate <60 mL/min/1.73 m2; HbA1c level =7.0%;
* International normalized ratio =1.2;
* hemoglobin <10 g/dL, platelets <100,000/µL, and white blood cells within the normal range;
* Clinically significant abnormalities in the urine analysis.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/06/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/2027
Actual
Sample size
Target
21
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Save Sight Institute - Sydney Eye Hospital - Sydney
Recruitment postcode(s) [1] 0 0
2000 - Sydney

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
PYC Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Sreenivasu Mudumba
Address 0 0
Country 0 0
Phone 0 0
510-423-2680
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06970106