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

NCT06970106 | Recruiting Phase 1 DMC

• 1 other identifier: PYC-001-CL-102
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 3

Brief Summary

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

Conditions

OPA1 Gene Mutation; Autosomal Dominant Optic Atrophy; Hereditary Optic Atrophies; Kjer Optic Atrophy

Outcome Measures

Primary Outcomes (23)

• [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 Outcomes (11)

• [All Cohorts] Change from Baseline in Best Corrected Visual Acuity (BCVA)/ High Contrast Visual Acuity (HCVA) and Low Contrast Visual Acuity (LCVA) scores

  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

Study Arms (6)

Cohort 1: Single Dose of 60ug

EXPERIMENTAL

A single dose of 60ug of PYC-001 administered intravitreally

Drug: PYC-001

Cohort 2: 10ug of PYC-001, 8 weeks

EXPERIMENTAL

Up to 6 doses of 10ug PYC-001, administered intravitreally in 8 weeks interval.

Drug: PYC-001

Cohort 3: 10ug of PYC-001, 12 weeks

EXPERIMENTAL

Up to 6 doses of 10ug PYC-001, administered intravitreally in 12 weeks interval

Drug: PYC-001

Cohort 4: 30ug of PYC-001, 8 weeks

EXPERIMENTAL

Up to 6 doses of 30ug PYC-001, administered intravitreally in 8 weeks interval

Drug: PYC-001

Cohort 5: 30ug of PYC-001, 12 weeks

EXPERIMENTAL

Up to 6 doses of 30ug PYC-001, administered intravitreally in 12 weeks interval

Drug: PYC-001

Cohort 6: 60ug of PYC-001, 12 weeks

EXPERIMENTAL

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

Interventions

PYC-001 DRUG

PYC-001 is a peptide-phosphorodiamidate morpholino oligonucleotide administered intravitreally

Cohort 1: Single Dose of 60ug; Cohort 2: 10ug of PYC-001, 8 weeks; Cohort 3: 10ug of PYC-001, 12 weeks; Cohort 4: 30ug of PYC-001, 8 weeks; Cohort 5: 30ug of PYC-001, 12 weeks; Cohort 6: 60ug of PYC-001, 12 weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must give written informed consent before any study-related activity is carried out
• Adult males and females, aged 18 years and above at screening;
• Body mass index ≥18.0 and ≤35.0 kg/m2
• 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.
• 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).
• 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)
• Medically healthy (in the opinion of the PI), as determined by pre-study medical history
• Female participants must be of non-childbearing potential or if female participants are of childbearing potential, they must:
• Have a negative pregnancy test at the screening visit and on study Day -1;
• 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;
• Agree to use adequate contraception
• Male participants must:
• Agree not to donate sperm
• If engaging in sexual intercourse with a female partner who could become pregnant, agree to use adequate contraception
• 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

You may not qualify if:

• Participant has a known allergy to PYC-001 or any of its excipients;
• 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;
• Females who are breastfeeding or planning to breastfeed;
• 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.
• Have received any prior cell or gene therapy for a retinal condition, excluding participation in study PYC-001-101;
• Within three months prior to study Day -1, have undergone any vitreoretinal surgery or any other ocular surgery in the study eye.
• Within three months prior to study Day -1, have placement of an Ozurdex® implant. T
• Within three years prior to study Day -1, have placement of Retisert® of Iluvien® implants.
• Have ocular media opacity or poor pupillary dilation prohibiting quality ophthalmic evaluation or photography, ;
• Macular edema (intraretinal, sub-retinal or other fluid) in the study eye requiring treatment.
• History of recurrent uveitis (idiopathic or immune-related) or active ocular inflammation;
• 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.
• Over-the-counter drugs like CoQ10 and other Nutraceutical usage will require a washout by five half-lives prior to baseline visit.
• Have a recent history (\<6 months) of or current excessive recreational drug or alcohol use, in the opinion of the PI.
• Positive alcohol breath test as assessed at screening, and on study Day -1 and study Day 1;

Sponsors & Collaborators

• PYC Therapeutics: lead

Study Sites (3)

Save Sight Institute - Sydney Eye Hospital

Sydney, New South Wales, 2000, Australia

RECRUITING

Cerulea Clinical Trials

East Melbourne, Australia

RECRUITING

Retina Specialists

Auckland, 1052, New Zealand

RECRUITING

MeSH Terms

Conditions

Optic Atrophy, Autosomal Dominant; Optic Atrophies, Hereditary

Condition Hierarchy (Ancestors)

Optic Atrophy; Optic Nerve Diseases; Cranial Nerve Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Eye Diseases, Hereditary; Eye Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Sreenivasu Mudumba

CONTACT

510-423-2680; adoa@pyctx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 10mcg and 30mcg dose groups will be enrolling in parallel. 60mcg dose enrollment will be sequential - SAD cohort will be filled first followed by 60mcg MAD (once safety review is completed)

Study Record Dates

• First Submitted: April 28, 2025
• First Posted: May 14, 2025
• Study Start: September 30, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: April 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1); AU (2)