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
This is a phase 1b open-label, randomized, single and repeat dose study to evaluate the safety and tolerability of IVT administered PYC-001 in participants with confirmed OPA1 mutation-associated ADOA. The primary objective of this study is to gather safety data and determine the optimal dosing regimen for PYC-001. The exploratory objectives of this study include evaluating the ocular structural and functional changes following multiple doses of IVT administered PYC-001. The PK profile of PYC-001 following multiple doses will also be assessed. In this open-label study, PYC-001 will be injected in a single eye and ocular safety will be assessed in both eyes.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
PYC-001 is a peptide-phosphorodiamidate morpholino oligonucleotide administered intravitreally
Save Sight Institute - Sydney Eye Hospital
Sydney, New South Wales, Australia
RECRUITINGCerulea Clinical Trials
East Melbourne, Australia
RECRUITINGRetina Specialists
Auckland, New Zealand
RECRUITING[All Cohorts] Number of participants experiencing treatment emergent adverse events
The incidence, type, severity, and relationship of treatment emergent ocular and non-ocular adverse events and treatment-emergent Serious Adverse Events will be recorded. An AE is any untoward medical occurrence in a clinical study participant that either occurs during the study or, if present predose, worsens during the study, and which does not necessarily have to have a causal relationship with the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease associated with study participation, whether or not considered related to the study treatment.
Time frame: Up to 96 weeks
[All Cohorts] Changes from baseline in vital signs (heart rate)
Time frame: Up to 96 weeks
[All Cohorts] Changes from baseline in vital signs (systolic and diastolic blood pressure)
Time frame: Up to 96 weeks
[All Cohorts] Changes from baseline in vital signs (tympanic temperature)
Time frame: Up to 96 weeks
[All Cohorts] Changes from baseline in vital signs (respiratory rate)
Time frame: Up to 96 weeks
[All Cohorts] Change from baseline in white blood cells (WBC), platelets, white blood cell count with differential neutrophil count, eosinophil count, basophil count, lymphocyte count, monocyte count
All measured in 10x\^9L
Time frame: Up to 96 weeks
[All Cohorts] Change from baseline in red blood cells
Units x 10\^12L
Time frame: Up to 96 weeks
[All Cohorts] Change from baseline in hemoglobin and mean corpuscular hemaglobin concentration
Units: grams per liter (g/L)
Time frame: Up to 96 weeks
[All Cohorts] Change from baseline in mean corpuscular volume and mean platelet volume
measured in femtoliter (fL)
Time frame: Up to 96 weeks
[All Cohorts] Change from baseline in hematocrit
Units: litres per litre (L/L)
Time frame: Up to 96 weeks
[All Cohorts] Change from baseline in mean corpuscular hemoglobin
Units: picograms (pg)
Time frame: Up to 96 weeks
[All Cohorts] Change from baseline in neutrophils, lymphocytes, monocytes, eosinophils, basophils and reticulocyte count
Units: %
Time frame: Up to 96 weeks
[All Cohorts] Change from baseline in Alanine Transaminase, Alkaline Phosphatase, Aspartate aminotransferase, Creatine Phosphokinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Amylase and Lipase
Units: units/Liter (U/L)
Time frame: Up to 96 weeks
[All Cohorts] Change from baseline in Bilirubin (total, direct and indirect) and creatinine
Units: micromoles per liter (mcmol/L)
Time frame: Up to 96 weeks
[All Cohorts] Change from baseline in protein, albumin, globulin and fibrinogen
Units:grams per liter (g/L)
Time frame: Up to 96 weeks
[All Cohorts] Change from baseline in Blood Urea Nitrogen (BUN), Sodium, Potassium, Chloride, Bicarbonate, Calcium, Magnesium, Phosphorous, Total Cholesterol, Triglyceride, HDL, LD. Uric Acid and Glucose
Units: millimoles per liter (mmol/L)
Time frame: Up to 96 weeks
[All Cohorts] Change from baseline in Anion Gap
Units: milliequivalents per liter (mEq/L)
Time frame: Up to 96 weeks
[All Cohorts] Change from baseline in Estimated Glomerular Filtration Rate (eGFR)
Time frame: Up to 96 weeks
[All Cohorts] Change from baseline in Prothrombin Time and Partial Thromboplastin Time, Activated (APTT)
Time frame: Up to 96 weeks
[All Cohorts] Change from baseline in Prothrombin Time (INR)
Time frame: Up to 96 weeks
[All Cohorts] Change from baseline in urinalysis (Protein, glucose, ketones, blood, bilirubin, leucocyte esterase and nitrites
Presence (positive, negative, trace) captured
Time frame: Up to 96 weeks
[All Cohorts] Change from baseline in urinalysis (pH)
Time frame: Up to 96 weeks
[All Cohorts] Change from baseline in urinalysis (specific gravity)
Time frame: Up to 96 weeks
[All Cohorts] Change from Baseline in Best Corrected Visual Acuity (BCVA)/ High Contrast Visual Acuity (HCVA) and Low Contrast Visual Acuity (LCVA) scores
Early Treatment Diabetic Retinopathy Study (ETDRS) optotypes used, letter score will be captured for BCVA/HCVa and LCVA.
Time frame: Up to 96 weeks
[All Cohorts] Change from Baseline in Visual field sensitivity by photopic static perimetry
Time frame: Up to 96 weeks
[All Cohorts] Change from Baseline in posterior eye health by fundus examination using ultrawide fundoscopy
Time frame: Up to 96 weeks
[All Cohorts] Change from Baseline in Color vision
Time frame: Up to 96 weeks
[All Cohorts] Change from Baseline in Contrast sensitivity by Pelli Robson chart
Time frame: Up to 96 weeks
[All Cohorts] Change from Baseline in Multifocal visual evoked potential OR Full field electroretinogram
Time frame: Up to 96 weeks
[All Cohorts] Change from Baseline in Retinal nerve fiber layer (RNFL) by spectral domain optical coherence tomography
Time frame: Up to 96 weeks
[All Cohorts] Change from Baseline for Ganglion Cell Layer (GCL) thickness determined by Spectral domain optical coherence tomography
Time frame: Up to 96 Weeks
[All Cohorts] Change from Baseline for Bruch's membrane opening (BMO) disc size, as determined by spectral domain optical coherence tomography
Time frame: Up to 96 weeks
[All Cohorts] Change from Baseline in Mitochondrial function test via flavoprotein fluorescence
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Up to 96 weeks
[Repeat Dose Cohorts] Plasma concentrations of PYC-001 following multiple dose intravitreally administered PYC-001
Time frame: Up to 96 weeks