SAD of IVT PYC-001 in OPA1 Mutation-Associated Autosomal Dominant Optic Atrophy (Sundew)

NCT06461286 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: PYC-001-101
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

A First-in-Human multi-centre, prospective, Phase1a, Single Ascending Dose (SAD) interventional study of PYC-001 in participants with confirmed OPA1 mutation (haploinsufficiency) associated ADOA.

Conditions

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

Outcome Measures

Primary Outcomes (12)

• Incidence, type, severity and relationship of ocular treatment-emergent adverse events (TEAEs), and treatment-emergent serious adverse events (SAEs) in the study eye

  24 weeks

• Incidence, type, severity and relationship of ocular treatment-emergent adverse events (TEAEs), and treatment-emergent serious adverse events (SAEs) in the study eye

  48 weeks

• Incidence, type, severity and relationship of ocular TEAEs, and treatment-emergent SAEs in the fellow eye

  24 weeks

• Incidence, type, severity and relationship of ocular TEAEs, and treatment-emergent SAEs in the fellow eye

  48 weeks

• Incidence, type, severity and relationship of non-ocular TEAEs, and treatment-emergent SAEs

  24 weeks

• Incidence, type, severity and relationship of non-ocular TEAEs, and treatment-emergent SAEs

  48 weeks

• Change from baseline for vital signs measurements (heart rate [HR], systolic and diastolic blood pressure [BP], tympanic temperature, respiratory rate [RR])

  48 weeks

• Change from baseline for 12-lead electrocardiogram (ECG) parameters

  Twelve-lead ECG (including but not limited to the measurements of ventricular HR, PR interval, QRS duration, QT interval and QtcF) will be performed. ECGs will be performed in triplicate at screening only with each replicate separated by at least 1 minute and the full set of triplicates completed within 5 minutes. The mean value for the triplicate will be utilized. Single ECGs will be collected at all other timepoints.

  48 weeks

• Change from baseline for clinical laboratory results - hematology

  Hematology Screening parameters: Hematocrit, Hemoglobin, Mean Corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular volume, mean platelet volume, packed cell volume, platelet count, red blood cell count, reticulocyte count, white blood cell count with differential neutrophil count, eosinophil count, basophil count, lymphocyte count, monocyte count.

  48 weeks

• Change from baseline for clinical laboratory results - clinical chemistry

  Clinical Chemistry screening parameters: Albumin, alkaline phosphatase, alanine aminotransferase, amylase, anion gap, aspartate aminotransferase, bicarbonate, calcium, ionized calcium, chloride, conjugated (direct) and unconjugated bilirubin, creatinine, eGFR, Creatinine kinase, Gamma glutamyl transferase, Globulin, Glucose, High density lipoprotein, Lactate dehydrogenase, Lipase, Low density lipoprotein, Magnesium, Phosphate, Potassium, Sodium, Total bilirubin, Total cholesterol, Total protein, Triglycerides, Urate, Urea

  48 weeks

• Change from baseline for clinical laboratory results - coagulation

  Coagulation screening parameters: Activated partial thromboplastin time, International normalized ratio/Prothrombin time, Fibrinogen

  48 weeks

• Change from baseline for clinical laboratory results - urinalysis

  Urinalysis screening parameters: Bilirubin, Blood, Glucose, Ketones, Leukocyte esterase, Nitrites, pH, Protein, Specific gravity, Urobilinogen

  48 weeks

Secondary Outcomes (11)

• Change from baseline for Best-corrected visual acuity (BCVA) letter score using Early Treatment of Diabetic Retinopathy Study(ETDRS)

  Week 4, Week 12, Week 24, Week 48

• Change from baseline for Low contrast visual acuity (LCVA)

  Week 4, Week 12, Week 24, Week 48

• Change from baseline for Perimetry

  Week 4, Week 12, Week 24, Week 48

• Change from baseline for posterior eye healthy by fundus examination, using ultrawide funduscopy

  Week 4, Week 12, Week 24, Week 48

• Change from baseline for color vision by Hardy Rand Rittler test

  Week 4, Week 12, Week 24, Week 48

Study Arms (1)

Single arm dose escalation study of PYC-001

EXPERIMENTAL

Drug: PYC-001 Phase 1a Open-Label, Single Ascending Dose Study to Evaluate the Safety and Tolerability of Intravitreally Administered PYC-001 in participants with Confirmed OPA1 Mutation-Associated Autosomal Dominant Optic Atrophy

Drug: PYC-001

Interventions

PYC-001 DRUG

Single Group Assignment

Single arm dose escalation study of PYC-001

Eligibility Criteria

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

You may qualify if:

• Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects;
• Adult males and females, aged 18 years and above at screening;
• Body mass index (BMI) ≥18.0 and ≤32.0 kg/m2, with a body weight ≤ 100kg at screening;
• Have a molecular (genetic) diagnosis of OPA1 mutation at screening;
• Have a clinical diagnosis of OPA1 mutation-associated ADOA at screening;
• Participants with BCVA of between 20/40 (70 ETDRS letters) and 20/160 (39-43 ETDRS letters). If both eyes meet this eligibility criteria, the eye with worse BCVA will be selected as the study eye and the other eye will be designated as the "fellow eye";
• Medically healthy (in the opinion of the Investigator), as determined by pre-study medical history, and without clinically significant abnormalities including:
• Physical examination without any clinically relevant findings;
• Systolic BP in the range of 90 to 160mmHg and diastolic BP in the range of 50 to 95 mmHg after 5 minutes in supine of semi-supine position;
• Heart rate in the range of 45 to 100 bpm after 5 minutes rest in supine or semi-supine position;
• Body temperature (tympanic), between 35.5°C and 37.7°C;
• ECG without clinically significant abnormalities including QT interval corrected for Fredericia (QTcF) \< 450 msec for male subjects and \< 470 msec for female subjects;
• No clinically significant findings in clinical chemistry, hematology, coagulation and urinalysis tests at screening.
• Have a negative pregnancy test at the screening visit, on study Day -1 and study Day 1 prior to dosing;
• Agree not to attempt to become pregnant or donate ova from signing the consent form until at least 130 days after IVT administration of PYC-001 and at least 30 days after the final dose of ANX776;

You may not qualify if:

• Participants has a known allergy to PYC-001 or any of its excipients;
• Demonstrated clinically significant co-morbidities, which, in the opinion of the Investigator, would interfere with the volunteer's ability to participate in the trial and/or confound study outcomes;
• Females who are breastfeeding or planning to breastfeed;
• Have mutations in genes that cause ADOA, other than OPA1 (for example in case of dominant negative ADOA) and ADOA Plus;
• Have received any prior cell or gene therapy for a retinal condition;
• Within 3 months prior to study Day -1, have undergone any vitreoretinal surgery (scleral buckle, pars plana vitrectomy, retrieval of a dropped nucleus or intraocular lens, radial optic neurotomy, sheathotomy, cyclodestructive procedures or multiple filtration surgeries \[2 or more\]) or any other ocular surgery;
• Within 3 months prior to study Day -1, have placement of an Ozurdex® implant;
• Within 3 months 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, as assessed by the Investigator;
• Have used any investigational drug or device within 90 days or 5 estimated half-lives of the investigational drug or device (whichever is longer) prior to study Day -1, or plan to participate in another study of a drug or device during the study period. Participation in observational trials is allowed based on Investigator discretion and consultation with the Sponsor's Medical Representative;
• Have a recent history (\< 6 months) of or current excessive recreational drug or alcohol use, in the opinion of the Investigator. Note: excessive alcohol use is defined as regular consumption of \> 10 standard drinks per week or \> 4 standard drinks per day, where 1 standard drink is defined as 10 grams of pure alcohol;
• Positive alcohol breath test as assessed at screening, and on study Day -1 and study Day 1;
• Positive urine drugs of abuse as assessed at screening and on study Day -1 and study Day 1;
• Any retinal pathology other than ADOA or any other condition or prior therapy that in the opinion of the Investigator would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.

Sponsors & Collaborators

• PYC Therapeutics: lead

Study Sites (2)

Save Sight Institute - Sydney Eye Hospital

Sydney, New South Wales, 2000, Australia

Location

Center for Eye Research Australia (CERA)

East Melbourne, Victoria, 3002, Australia

Location

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

Study Officials

• Sreenivasu Mudumba, PhD

  PYC Therapeutics

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: June 5, 2024
• First Posted: June 14, 2024
• Study Start: October 31, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: January 21, 2026

Record last verified: 2026-01

Locations

AU (2)