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

Status: Recruiting
Location: See all (2) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
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 21 participants from across UK and Australia 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 8 weeks 7. Three doses of 60ug PYC-001 at an interval of 12 weeks

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Must give written informed consent before any study-related activity is carried out and must be able to understand the full nature and purpose of the study, including possible risks and adverse effects;

• 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. In case of complex mutation profile, eligibility will be determined in consultation with the Sponsor. Rollover participants are exempt from this criterion as their genetic diagnosis was confirmed in PYC-001-101;

• 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). If both eyes meet this eligibility criteria, the eye with better fixation as determined by the PI in consultation with the Sponsor will be selected as the study eye and the other eye will be designated as the fellow eye. In the event that both eyes are eligible and have adequate fixation to reliably perform all study assessments, the worse eye as determined by the physician will be taken as the study eye.

• PYC-001-101 participants are exempt from this criterion and will have the same study eye and fellow eye as determined in PYC-001-101;

• Treatment Naïve participants (participants from PYC-001-101 are exempt from this criterion) 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), specifically the outer ring (T, TS, NS, N, NI and TI), defined as:

∙ Mild disease = RNFL abnormalities (outside normal range) in no more than one of six sectors;

‣ Moderate disease = RNFL abnormalities (outside normal range) in no more than three of six sectors;

‣ Severe disease = RNFL abnormalities (outside normal range) in four of six sectors;

‣ Advanced disease = RNFL abnormalities (outside normal range) in six of six sectors;

• Medically healthy (in the opinion of the PI), as determined by pre-study medical history, and without clinically significant abnormalities including (assessments may be repeated at the discretion of the PI if an out-of-range value is determined to be erroneous):

∙ Physical examination without any clinically relevant findings;

‣ Systolic blood pressure (BP) in the range of 90 to 160 mmHg and diastolic BP in the range of 50 to 95 mmHg after five minutes in sitting or supine or semi-supine position;

‣ Heart rate (HR) in the range of 45 to 110 bpm after five minutes rest in sitting or supine or semi-supine position;

‣ Body temperature (tympanic), between 35.5°C and 37.7°C;

‣ No clinically significant findings in clinical chemistry, hematology, coagulation and urinalysis tests at screening .

• Female participants must be of non-childbearing potential, i.e., surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least six 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 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 (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 130 days after final IVT dose administration of PYC-001 , if not exclusively in a same-sex relationship or abstinent as a committed lifestyle.

• Male participants must:

∙ Agree not to donate sperm from signing the consent form until at least 190 days after final IVT dose administration of PYC-001;

‣ 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 (defined in Appendix 13.1) from signing the consent form until at least 190 days after final IVT dose administration of PYC-001;

‣ 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 from signing the consent form until at least 190 days after final IVT dose administration of PYC-001 and;

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

Locations
Other Locations
Australia
Cerulea Clinical Trials
RECRUITING
East Melbourne
Save Sight Institute - Sydney Eye Hospital
RECRUITING
Sydney
Contact Information
Primary
Sreenivasu Mudumba
adoa@pyctx.com
510-423-2680
Time Frame
Start Date: 2025-09-30
Estimated Completion Date: 2027-01-01
Participants
Target number of participants: 21
Treatments
Experimental: Cohort 1: Single Dose of 60ug
A single dose of 60ug of PYC-001 administered intravitreally
Experimental: Cohort 2: 10ug of PYC-001, 8 weeks
3 doses of 10ug PYC-001, administered intravitreally in 8 weeks interval
Experimental: Cohort 3: 10ug of PYC-001, 12 weeks
3 doses of 10ug PYC-001, administered intravitreally in 12 weeks interval
Experimental: Cohort 4: 30ug of PYC-001, 8 weeks
3 doses of 30ug PYC-001, administered intravitreally in 8 weeks interval
Experimental: Cohort 5: 30ug of PYC-001, 12 weeks
3 doses of 30ug PYC-001, administered intravitreally in 12 weeks interval
Experimental: Cohort 6: 60ug of PYC-001, 8 weeks
Following SRC, Single dose participant can continue to receive 3 doses of 60ug PYC-001, administered intravitreally at 8 weeks interval
Experimental: Cohort 7: 60ug of PYC-001, 12 weeks
Following SRC, Single dose participant can continue to receive 3 doses of 60ug PYC-001, administered intravitreally at 12 weeks interval
Related Therapeutic Areas
Sponsors
Leads: PYC Therapeutics

This content was sourced from clinicaltrials.gov