SAD of IVT PYC-001 in OPA1 Mutation-Associated Autosomal Dominant Optic Atrophy (Sundew)
NCT Number: NCT06461286
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: OPA1 Gene Mutation|Autosomal Dominant Optic Atrophy|Hereditary Optic Atrophies|Kjer Optic Atrophy
Interventions: DRUG: PYC-001
Sponsor: PYC Therapeutics
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 18
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07
Completion Date: 2025-08

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.

Primary Outcome Measures: 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 Outcome Measures: 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|Change from baseline for contrast sensitivity by Pelli Robson Chart, Week 4, Week 12, Week 24, Week 48|Change from baseline for visual field sensitivity by Static Perimetry, Week 4, Week 12, Week 24, Week 48|Change from baseline for Multifocal Visual Evoked Potential (mfVEP), Week 4, Week 12, Week 24, Week 48|Change from baseline for retinal nerve fiber layer (RNFL) and Ganglion Cell Layer (GCL) thickness by Spectral domain optical coherence tomography (SD-OCT), Week 4, Week 12, Week 24, Week 48|Change from baseline for mitochondrial function test by flavoprotein fluorescence (FPF) analyzer (Ocumet Beacon), Week 4, Week 12, Week 24, Week 48|Change from baseline for Detection of Apoptosis in Retinal Cells (DARC), Week 4, Week 12, Week 24, Week 48