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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06461286




Registration number
NCT06461286
Ethics application status
Date submitted
5/06/2024
Date registered
14/06/2024
Date last updated
21/11/2024

Titles & IDs
Public title
SAD of IVT PYC-001 in OPA1 Mutation-Associated Autosomal Dominant Optic Atrophy (Sundew)
Scientific title
A Phase 1a Open-Label, Single Ascending Dose Study to Evaluate the 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-001-101
Universal Trial Number (UTN)
Trial acronym
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: Single arm dose escalation study of PYC-001 - Drug: PYC-001

Phase 1a Open-Label, Single Ascending Dose Study to Evaluate the Safety and Tolerability of Intravitreally Administered PYC-001 in participants with Confirmed OPA1 Mutation-Associated Autosomal Dominant Optic Atrophy


Treatment: Drugs: PYC-001
Single Group Assignment

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence, type, severity and relationship of ocular treatment-emergent adverse events (TEAEs), and treatment-emergent serious adverse events (SAEs) in the study eye
Timepoint [1] 0 0
24 weeks
Primary outcome [2] 0 0
Incidence, type, severity and relationship of ocular treatment-emergent adverse events (TEAEs), and treatment-emergent serious adverse events (SAEs) in the study eye
Timepoint [2] 0 0
48 weeks
Primary outcome [3] 0 0
Incidence, type, severity and relationship of ocular TEAEs, and treatment-emergent SAEs in the fellow eye
Timepoint [3] 0 0
24 weeks
Primary outcome [4] 0 0
Incidence, type, severity and relationship of ocular TEAEs, and treatment-emergent SAEs in the fellow eye
Timepoint [4] 0 0
48 weeks
Primary outcome [5] 0 0
Incidence, type, severity and relationship of non-ocular TEAEs, and treatment-emergent SAEs
Timepoint [5] 0 0
24 weeks
Primary outcome [6] 0 0
Incidence, type, severity and relationship of non-ocular TEAEs, and treatment-emergent SAEs
Timepoint [6] 0 0
48 weeks
Primary outcome [7] 0 0
Change from baseline for vital signs measurements (heart rate [HR], systolic and diastolic blood pressure [BP], tympanic temperature, respiratory rate [RR])
Timepoint [7] 0 0
48 weeks
Primary outcome [8] 0 0
Change from baseline for 12-lead electrocardiogram (ECG) parameters
Timepoint [8] 0 0
48 weeks
Primary outcome [9] 0 0
Change from baseline for clinical laboratory results - hematology
Timepoint [9] 0 0
48 weeks
Primary outcome [10] 0 0
Change from baseline for clinical laboratory results - clinical chemistry
Timepoint [10] 0 0
48 weeks
Primary outcome [11] 0 0
Change from baseline for clinical laboratory results - coagulation
Timepoint [11] 0 0
48 weeks
Primary outcome [12] 0 0
Change from baseline for clinical laboratory results - urinalysis
Timepoint [12] 0 0
48 weeks
Secondary outcome [1] 0 0
Change from baseline for Best-corrected visual acuity (BCVA) letter score using Early Treatment of Diabetic Retinopathy Study(ETDRS)
Timepoint [1] 0 0
Week 4, Week 12, Week 24, Week 48
Secondary outcome [2] 0 0
Change from baseline for Low contrast visual acuity (LCVA)
Timepoint [2] 0 0
Week 4, Week 12, Week 24, Week 48
Secondary outcome [3] 0 0
Change from baseline for Perimetry
Timepoint [3] 0 0
Week 4, Week 12, Week 24, Week 48
Secondary outcome [4] 0 0
Change from baseline for posterior eye healthy by fundus examination, using ultrawide funduscopy
Timepoint [4] 0 0
Week 4, Week 12, Week 24, Week 48
Secondary outcome [5] 0 0
Change from baseline for color vision by Hardy Rand Rittler test
Timepoint [5] 0 0
Week 4, Week 12, Week 24, Week 48
Secondary outcome [6] 0 0
Change from baseline for contrast sensitivity by Pelli Robson Chart
Timepoint [6] 0 0
Week 4, Week 12, Week 24, Week 48
Secondary outcome [7] 0 0
Change from baseline for visual field sensitivity by Static Perimetry
Timepoint [7] 0 0
Week 4, Week 12, Week 24, Week 48
Secondary outcome [8] 0 0
Change from baseline for Multifocal Visual Evoked Potential (mfVEP)
Timepoint [8] 0 0
Week 4, Week 12, Week 24, Week 48
Secondary outcome [9] 0 0
Change from baseline for retinal nerve fiber layer (RNFL) and Ganglion Cell Layer (GCL) thickness by Spectral domain optical coherence tomography (SD-OCT)
Timepoint [9] 0 0
Week 4, Week 12, Week 24, Week 48
Secondary outcome [10] 0 0
Change from baseline for mitochondrial function test by flavoprotein fluorescence (FPF) analyzer (Ocumet Beacon)
Timepoint [10] 0 0
Week 4, Week 12, Week 24, Week 48
Secondary outcome [11] 0 0
Change from baseline for Detection of Apoptosis in Retinal Cells (DARC)
Timepoint [11] 0 0
Week 4, Week 12, Week 24, Week 48

Eligibility
Key inclusion criteria
1. 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;
2. Adult males and females, aged 18 years and above at screening;
3. Body mass index (BMI) =18.0 and =32.0 kg/m2, with a body weight = 100kg at screening;
4. Have a molecular (genetic) diagnosis of OPA1 mutation at screening;
5. Have a clinical diagnosis of OPA1 mutation-associated ADOA at screening;
6. Participants with BCVA of between 20/40 (70 ETDRS letters) and 20/160 (39-43 ETDRS letters). If both eyes meet this eligibility criteria, the eye with worse BCVA will be selected as the study eye and the other eye will be designated as the "fellow eye";
7. Medically healthy (in the opinion of the Investigator), as determined by pre-study medical history, and without clinically significant abnormalities including:

1. Physical examination without any clinically relevant findings;
2. Systolic BP in the range of 90 to 160mmHg and diastolic BP in the range of 50 to 95 mmHg after 5 minutes in supine of semi-supine position;
3. Heart rate in the range of 45 to 100 bpm after 5 minutes rest in supine or semi-supine position;
4. Body temperature (tympanic), between 35.5°C and 37.7°C;
5. ECG without clinically significant abnormalities including QT interval corrected for Fredericia (QTcF) < 450 msec for male subjects and < 470 msec for female subjects;
6. No clinically significant findings in clinical chemistry, hematology, coagulation and urinalysis tests at screening.
8. Female volunteers must be of non-child-bearing potential, i.e., surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy 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 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 child-bearing potential, they must:

1. Have a negative pregnancy test at the screening visit, on study Day -1 and study Day 1 prior to dosing;
2. Agree not to attempt to become pregnant or donate ova from signing the consent form until at least 130 days after IVT administration of PYC-001 and at least 30 days after the final dose of ANX776;
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 30 days after the final dose of ANX776 (study Day 336), if not exclusively in a same-sex relationship or abstinent as a committed lifestyle.
9. Male volunteers must:

1. Agree not to donate sperm from signing the consent form until at least 190 days after IVT administration of PYC-001 and at least 90 days after the final dose of ANX776;
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 IVT administration of PYC-001 and at least 90 days after the final dose of ANX776;
3. If engaging in sexual intercourse with a female partner who is not of child-bearing potential or a same-sex partner, agree to use a condom from signing the consent form until at least 190 days after IVT administration of PYC-001 and at least 90 days after the final dose of ANX776;
10. Have suitable venous access for blood sampling
11. Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participants has a known allergy to PYC-001 or any of its excipients;
2. Demonstrated clinically significant co-morbidities, which, in the opinion of the Investigator, would interfere with the volunteer's ability to participate in the trial and/or confound study outcomes;
3. Females who are breastfeeding or planning to breastfeed;
4. Have mutations in genes that cause ADOA, other than OPA1 (for example in case of dominant negative ADOA) and ADOA Plus;
5. Have received any prior cell or gene therapy for a retinal condition;
6. Within 3 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 [2 or more]) or any other ocular surgery;
7. Within 3 months prior to study Day -1, have placement of an Ozurdex® implant;
8. Within 3 months prior to study Day -1 have placement of Retisert® of Iluvien® implants;
9. Have ocular media opacity or poor pupillary dilation prohibiting quality ophthalmic evaluation or photography, as assessed by the Investigator;
10. Macular edema (intraretinal, sub-retinal or other fluid) requiring regular treatment at a frequency of less than every 6 weeks; macular edema must be stable for at least 3 months prior to screening. Note, the above conditions will be permitted for inclusion if, in the opinion of the Investigator and in consultation with the SMM, they will not interfere with study evaluations, or have resolved by study Day -1 prior to dose administration;
11. Have used any investigational drug or device within 90 days or 5 estimated half-lives of the investigational drug or device (whichever is longer) prior to study Day -1, or plan to participate in another study of a drug or device during the study period. Participation in observational trials is allowed based on Investigator discretion and consultation with the Sponsor's Medical Representative;
12. 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;
13. Positive alcohol breath test as assessed at screening, and on study Day -1 and study Day 1;
14. Positive urine drugs of abuse as assessed at screening and on study Day -1 and study Day 1;
15. Any retinal pathology other than ADOA or 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
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
Sreenivasu Mudumba, PhD
Address 0 0
PYC Therapeutics
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
sri.mudumba@pyctx.com
Contact person for scientific queries

No information has been provided regarding IPD availability


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.