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
• 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
⁃ Willing and able to comply with all study assessments and protocol schedule/ restrictions