PYC-001 eye injections for people with OPA1-related autosomal dominant optic atrophy

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 trial tests whether injections of PYC-001 into one eye are safe and what dosing schedule works best for adults with OPA1 mutation–related autosomal dominant optic atrophy.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: PYC Therapeutics (industry)
• Locations: 3 sites (Sydney, New South Wales and 2 other locations)
• Trial ID: NCT06970106 on ClinicalTrials.gov

What this trial studies

This is an open-label, randomized phase 1b/2 study giving single and repeat intravitreal (IVT) injections of PYC-001 to participants with confirmed OPA1 haploinsufficiency. Participants are assigned to one of several dosing regimens (a single 60 µg dose or repeated 10, 30, or 60 µg doses at specified intervals) with dose escalation guided by a safety review committee. The primary focus is safety and tolerability and to identify the optimal dosing schedule; exploratory measures include ocular structure and function changes and pharmacokinetics after multiple doses. About 18 treatment-naïve adults from sites in Australia, New Zealand and nearby APAC locations will be enrolled, with injections given in a single study eye and both eyes monitored for safety.

Who should consider this trial

Good fit: Adults (≥18 years) with a confirmed OPA1 mutation (haploinsufficiency), treatment‑naïve, best-corrected visual acuity roughly between 20/40 and 20/200 with mild-to-moderate visual field and RNFL loss in the study eye, BMI 18–35, and otherwise medically healthy are the intended participants.

Not a fit: People without a confirmed OPA1 mutation, those with vision outside the specified acuity range or advanced optic nerve loss, those who have received prior related treatments, or who have exclusionary medical conditions (including pregnancy) are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If safe and appropriately dosed, PYC-001 injections could slow or stabilize vision loss in people with OPA1-related ADOA by targeting the underlying genetic defect.

How similar studies have performed: Genetic and intravitreal therapies for other inherited retinal diseases have shown promise, but OPA1-directed treatments are largely novel and clinical data specific to this approach are limited.

Eligibility criteria

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

Where this trial is running

Sydney, New South Wales and 2 other locations

• Save Sight Institute - Sydney Eye Hospital — Sydney, New South Wales, Australia (RECRUITING)
• Cerulea Clinical Trials — East Melbourne, Australia (RECRUITING)
• Retina Specialists — Auckland, New Zealand (RECRUITING)

Study contacts

• Study coordinator: Sreenivasu Mudumba

Conditions: OPA1 Gene Mutation, Autosomal Dominant Optic Atrophy, Hereditary Optic Atrophies, Kjer Optic Atrophy