Safety of Single and Repeat Dose of PYC-001 Eye Injections in People With Autosomal Dominant Optic Atrophy (Myrtle) (PYC-001-CL-102)

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

This study aims to gather safety data and determine the optimal dosing regimen for PYC-001 in participants with confirmed OPA1 mutation-associated ADOA. Approximately 18 participants from Australia, New Zealand, and other APAC countries are expected to be enrolled, depending on safety review committee (SRC) throughout the course of the study.

Participants may be assigned to any of the following:

1. A single 60ug dose of PYC-001
2. Three doses of 10ug PYC-001 at an interval of 8 weeks
3. Three doses of 10ug PYC-001 at an interval of 12 weeks
4. Three doses of 30ug PYC-001 at an interval of 8 weeks

5. Three doses of 30ug PYC-001 at an interval of 12 weeks

   Following completion of the 4 week safety review of the single 60ug of PYC-001 cohort, and if the 60 μg dose level is deemed safe by the SRC, the following cohorts will also be available:

6. Three doses of 60ug PYC-001 at an interval of 12 weeks

Study Overview

• Status: Recruiting
• Conditions: Autosomal Dominant Optic Atrophy; Kjer Optic Atrophy; OPA1 Gene Mutation; Hereditary Optic Atrophies
• Intervention / Treatment: Drug: PYC-001

Detailed Description

This is a phase 1b open-label, randomized, single and repeat dose study to evaluate the safety and tolerability of IVT administered PYC-001 in participants with confirmed OPA1 mutation-associated ADOA.

The primary objective of this study is to gather safety data and determine the optimal dosing regimen for PYC-001.

The exploratory objectives of this study include evaluating the ocular structural and functional changes following multiple doses of IVT administered PYC-001. The PK profile of PYC-001 following multiple doses will also be assessed.

In this open-label study, PYC-001 will be injected in a single eye and ocular safety will be assessed in both eyes.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sreenivasu Mudumba; Phone Number: 510-423-2680; Email: adoa@pyctx.com

Study Locations

• Australia
  • East Melbourne, Australia
    • Recruiting
    • Cerulea Clinical Trials
    • Principal Investigator: Doron Hickey
    • Contact: Stefanie Mulabegovic; Phone Number: +61 3 9959 0063; Email: smulabegovic@ceruleaclinicaltrials.org.au
  • New South Wales
    • Sydney, New South Wales, Australia, 2000
      • Recruiting
      • Save Sight Institute - Sydney Eye Hospital
      • Principal Investigator: Clare Fraser
      • Contact: Chanel Ling; Phone Number: +61 02 9382 7309; Email: myrtle.mrg.coordinator@groups.sydney.edu.au
• New Zealand
  • Auckland, New Zealand, 1052
    • Recruiting
    • Retina Specialists
    • Contact: Zanelle Angelo; Phone Number: +6493072020; Email: nurses@retinaspecialists.co.nz
    • Principal Investigator: Andrea Vincent

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Must give written informed consent before any study-related activity is carried out
2. Adult males and females, aged 18 years and above at screening;
3. Body mass index ≥18.0 and ≤35.0 kg/m2
4. Have a recent (within five years) genetic diagnosis of OPA1 mutation-associated (haploinsufficiency) ADOA and/or confirmed diagnosis during pre-screening or screening, as determined by the PI.
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).
6. Treatment Naïve participants 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)
7. Medically healthy (in the opinion of the PI), as determined by pre-study medical history

8. Female participants must be of non-childbearing potential or 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

9. Male participants must:

   1. Agree not to donate sperm
   2. If engaging in sexual intercourse with a female partner who could become pregnant, agree to use adequate contraception
   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
10. Willing and able to comply with all study assessments and protocol schedule/ restrictions

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 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.
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 or any other ocular surgery in the study eye.
7. Within three months prior to study Day -1, have placement of an Ozurdex® implant. T
8. Within three years 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, ;
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, Vitamin B6, Vitamin B12, A decision will be made on a case-by-case basis by the PI in consultation with the Sponsor.
13. Over-the-counter drugs like CoQ10 and other Nutraceutical usage will require a washout by five half-lives prior to baseline visit.
14. Have a recent history (<6 months) of or current excessive recreational drug or alcohol use, in the opinion of the PI.
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
18. Presence of illness or pathology that, per investigator, include symptoms and/or the associated treatments that can alter visual function including current ocular infection.
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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Single Dose of 60ug; A single dose of 60ug of PYC-001 administered intravitreally	Drug: PYC-001; PYC-001 is a peptide-phosphorodiamidate morpholino oligonucleotide administered intravitreally
Experimental: Cohort 2: 10ug of PYC-001, 8 weeks; Up to 6 doses of 10ug PYC-001, administered intravitreally in 8 weeks interval.	Drug: PYC-001; PYC-001 is a peptide-phosphorodiamidate morpholino oligonucleotide administered intravitreally
Experimental: Cohort 3: 10ug of PYC-001, 12 weeks; Up to 6 doses of 10ug PYC-001, administered intravitreally in 12 weeks interval	Drug: PYC-001; PYC-001 is a peptide-phosphorodiamidate morpholino oligonucleotide administered intravitreally
Experimental: Cohort 4: 30ug of PYC-001, 8 weeks; Up to 6 doses of 30ug PYC-001, administered intravitreally in 8 weeks interval	Drug: PYC-001; PYC-001 is a peptide-phosphorodiamidate morpholino oligonucleotide administered intravitreally
Experimental: Cohort 5: 30ug of PYC-001, 12 weeks; Up to 6 doses of 30ug PYC-001, administered intravitreally in 12 weeks interval	Drug: PYC-001; PYC-001 is a peptide-phosphorodiamidate morpholino oligonucleotide administered intravitreally
Experimental: Cohort 6: 60ug of PYC-001, 12 weeks; Following SRC, Single dose participant can continue to receive Up to 6 doses of 60ug PYC-001, administered intravitreally at 12 weeks interval; alternatively, treatment naive participants can be enrolled (once SRC is complete) to receive up to 6 doses	Drug: PYC-001; PYC-001 is a peptide-phosphorodiamidate morpholino oligonucleotide administered intravitreally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[All Cohorts] Number of participants experiencing treatment emergent adverse events	The incidence, type, severity, and relationship of treatment emergent ocular and non-ocular adverse events and treatment-emergent Serious Adverse Events will be recorded. An AE is any untoward medical occurrence in a clinical study participant that either occurs during the study or, if present predose, worsens during the study, and which does not necessarily have to have a causal relationship with the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease associated with study participation, whether or not considered related to the study treatment.	Up to 96 weeks
[All Cohorts] Changes from baseline in vital signs (heart rate)		Up to 96 weeks
[All Cohorts] Changes from baseline in vital signs (systolic and diastolic blood pressure)		Up to 96 weeks
[All Cohorts] Changes from baseline in vital signs (tympanic temperature)		Up to 96 weeks
[All Cohorts] Changes from baseline in vital signs (respiratory rate)		Up to 96 weeks
[All Cohorts] Change from baseline in white blood cells (WBC), platelets, white blood cell count with differential neutrophil count, eosinophil count, basophil count, lymphocyte count, monocyte count	All measured in 10x^9L	Up to 96 weeks
[All Cohorts] Change from baseline in red blood cells	Units x 10^12L	Up to 96 weeks
[All Cohorts] Change from baseline in hemoglobin and mean corpuscular hemaglobin concentration	Units: grams per liter (g/L)	Up to 96 weeks
[All Cohorts] Change from baseline in mean corpuscular volume and mean platelet volume	measured in femtoliter (fL)	Up to 96 weeks
[All Cohorts] Change from baseline in hematocrit	Units: litres per litre (L/L)	Up to 96 weeks
[All Cohorts] Change from baseline in mean corpuscular hemoglobin	Units: picograms (pg)	Up to 96 weeks
[All Cohorts] Change from baseline in neutrophils, lymphocytes, monocytes, eosinophils, basophils and reticulocyte count	Units: %	Up to 96 weeks
[All Cohorts] Change from baseline in Alanine Transaminase, Alkaline Phosphatase, Aspartate aminotransferase, Creatine Phosphokinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Amylase and Lipase	Units: units/Liter (U/L)	Up to 96 weeks
[All Cohorts] Change from baseline in Bilirubin (total, direct and indirect) and creatinine	Units: micromoles per liter (mcmol/L)	Up to 96 weeks
[All Cohorts] Change from baseline in protein, albumin, globulin and fibrinogen	Units:grams per liter (g/L)	Up to 96 weeks
[All Cohorts] Change from baseline in Blood Urea Nitrogen (BUN), Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphorous, Total Cholesterol, Triglyceride, HDL, LD. Uric Acid and Glucose	Units: millimoles per liter (mmol/L)	Up to 96 weeks
[All Cohorts] Change from baseline in Anion Gap	Units: milliequivalents per liter (mEq/L)	Up to 96 weeks
[All Cohorts] Change from baseline in Estimated Glomerular Filtration Rate (eGFR)		Up to 96 weeks
[All Cohorts] Change from baseline in Prothrombin Time and Partial Thromboplastin Time, Activated (APTT)		Up to 96 weeks
[All Cohorts] Change from baseline in Prothrombin Time (INR)		Up to 96 weeks
[All Cohorts] Change from baseline in urinalysis (Protein, glucose, ketones, blood, bilirubin, leucocyte esterase and nitrites	Presence (positive, negative, trace) captured	Up to 96 weeks
[All Cohorts] Change from baseline in urinalysis (pH)		Up to 96 weeks
[All Cohorts] Change from baseline in urinalysis (specific gravity)		Up to 96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[All Cohorts] Change from Baseline in Best Corrected Visual Acuity (BCVA)/ High Contrast Visual Acuity (HCVA) and Low Contrast Visual Acuity (LCVA) scores	Early Treatment Diabetic Retinopathy Study (ETDRS) optotypes used, letter score will be captured for BCVA/HCVa and LCVA.	Up to 96 weeks
[All Cohorts] Change from Baseline in Visual field sensitivity by photopic static perimetry		Up to 96 weeks
[All Cohorts] Change from Baseline in posterior eye health by fundus examination using ultrawide fundoscopy		Up to 96 weeks
[All Cohorts] Change from Baseline in Color vision		Up to 96 weeks
[All Cohorts] Change from Baseline in Contrast sensitivity by Pelli Robson chart		Up to 96 weeks
[All Cohorts] Change from Baseline in Multifocal visual evoked potential OR Full field electroretinogram		Up to 96 weeks
[All Cohorts] Change from Baseline in Retinal nerve fiber layer (RNFL) by spectral domain optical coherence tomography		Up to 96 weeks
[All Cohorts] Change from Baseline for Ganglion Cell Layer (GCL) thickness determined by Spectral domain optical coherence tomography		Up to 96 Weeks
[All Cohorts] Change from Baseline for Bruch's membrane opening (BMO) disc size, as determined by spectral domain optical coherence tomography		Up to 96 weeks
[All Cohorts] Change from Baseline in Mitochondrial function test via flavoprotein fluorescence		Up to 96 weeks
[Repeat Dose Cohorts] Plasma concentrations of PYC-001 following multiple dose intravitreally administered PYC-001		Up to 96 weeks

Collaborators and Investigators

• Sponsor: PYC Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: April 28, 2025
• First Submitted That Met QC Criteria: May 5, 2025
• First Posted (Actual): May 14, 2025

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Metabolic Diseases; Eye Diseases; Neurodegenerative Diseases; Eye Diseases, Hereditary; Heredodegenerative Disorders, Nervous System; Optic Nerve Diseases; Cranial Nerve Diseases; Mitochondrial Diseases; Optic Atrophy; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Optic Atrophy, Autosomal Dominant; Optic Atrophies, Hereditary
• Other Study ID Numbers: PYC-001-CL-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No