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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 4
- 主要终点
- [All Cohorts] Number of participants experiencing treatment emergent adverse events
研究概览
简要总结
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:
- A single 60ug dose of PYC-001
- Three doses of 10ug PYC-001 at an interval of 8 weeks
- Three doses of 10ug PYC-001 at an interval of 12 weeks
- Three doses of 30ug PYC-001 at an interval of 8 weeks
- 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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Participant has a known allergy to PYC-001 or any of its excipients;
- •Demonstrated clinically significant co-morbidities, which, in the opinion of the PI, would interfere with the participant's ability to participate in the study and/or confound study outcomes;
- •Females who are breastfeeding or planning to breastfeed;
- •Based on recent genetic testing, the participant has mutations in genes that cause ADOA, other than OPA1 (for example in case of dominant negative ADOA and ADOA Plus) or has other pathological variants that result in an ADOA-like optic atrophic phenotype or other pathologic genetic findings indicating presence of additional confounding ocular diseases based on comprehensive genetic screening.
- •Have received any prior cell or gene therapy for a retinal condition, excluding participation in study PYC-001-101;
- •Within three months prior to study Day -1, have undergone any vitreoretinal surgery or any other ocular surgery in the study eye.
- •Within three months prior to study Day -1, have placement of an Ozurdex® implant. T
- •Within three years 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, ;
- •Macular edema (intraretinal, sub-retinal or other fluid) in the study eye requiring treatment.
- •History of recurrent uveitis (idiopathic or immune-related) or active ocular inflammation;
- •Have used within 30 days of the Screening visit or is using any investigational drug or over-the-counter drug such as Idebenone, Vitamin B6, Vitamin B12, A decision will be made on a case-by-case basis by the PI in consultation with the Sponsor.
- •Over-the-counter drugs like CoQ10 and other Nutraceutical usage will require a washout by five half-lives prior to baseline visit.
- •Have a recent history (<6 months) of or current excessive recreational drug or alcohol use, in the opinion of the PI.
- •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 PI would make the volunteer unsuitable for this study
- •Presence of illness or pathology that, per investigator, include symptoms and/or the associated treatments that can alter visual function including current ocular infection.
- •Positive test for human immunodeficiency virus, hepatitis B or C virus;
- •Clinically significant findings in clinical chemistry, hematology, coagulation and urinalysis tests at screening
研究组 & 干预措施
Cohort 3: 10ug of PYC-001, 12 weeks
Up to 12 doses of 10ug PYC-001, administered intravitreally in 12 weeks interval
干预措施: PYC-001 (Drug)
Cohort 5: 30ug of PYC-001, 12 weeks
Up to 12 doses of 30ug PYC-001, administered intravitreally in 12 weeks interval
干预措施: PYC-001 (Drug)
Cohort 6: 60ug of PYC-001, 12 weeks
Following SRC, Single dose participant can continue to receive Up to 12 doses of 60ug PYC-001, administered intravitreally at 12 weeks interval; alternatively, treatment naive participants can be enrolled (once SRC is complete) to receive up to 12 doses
干预措施: PYC-001 (Drug)
Cohort 2: 10ug of PYC-001, 8 weeks
Up to 12 doses of 10ug PYC-001, administered intravitreally in 8 weeks interval.
干预措施: PYC-001 (Drug)
Cohort 1: Single Dose of 60ug
A single dose of 60ug of PYC-001 administered intravitreally
干预措施: PYC-001 (Drug)
Cohort 4: 30ug of PYC-001, 8 weeks
Up to 12 doses of 30ug PYC-001, administered intravitreally in 8 weeks interval
干预措施: PYC-001 (Drug)
结局指标
主要结局
[All Cohorts] Number of participants experiencing treatment emergent adverse events
时间窗: Up to 96 weeks
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.
[All Cohorts] Changes from baseline in vital signs (heart rate)
时间窗: Up to 96 weeks
[All Cohorts] Changes from baseline in vital signs (systolic and diastolic blood pressure)
时间窗: Up to 96 weeks
[All Cohorts] Changes from baseline in vital signs (tympanic temperature)
时间窗: Up to 96 weeks
[All Cohorts] Changes from baseline in vital signs (respiratory rate)
时间窗: 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
时间窗: Up to 96 weeks
All measured in 10x\^9L
[All Cohorts] Change from baseline in red blood cells
时间窗: Up to 96 weeks
Units x 10\^12L
[All Cohorts] Change from baseline in hemoglobin and mean corpuscular hemaglobin concentration
时间窗: Up to 96 weeks
Units: grams per liter (g/L)
[All Cohorts] Change from baseline in mean corpuscular volume and mean platelet volume
时间窗: Up to 96 weeks
measured in femtoliter (fL)
[All Cohorts] Change from baseline in hematocrit
时间窗: Up to 96 weeks
Units: litres per litre (L/L)
[All Cohorts] Change from baseline in mean corpuscular hemoglobin
时间窗: Up to 96 weeks
Units: picograms (pg)
[All Cohorts] Change from baseline in neutrophils, lymphocytes, monocytes, eosinophils, basophils and reticulocyte count
时间窗: Up to 96 weeks
Units: %
[All Cohorts] Change from baseline in Alanine Transaminase, Alkaline Phosphatase, Aspartate aminotransferase, Creatine Phosphokinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Amylase and Lipase
时间窗: Up to 96 weeks
Units: units/Liter (U/L)
[All Cohorts] Change from baseline in Bilirubin (total, direct and indirect) and creatinine
时间窗: Up to 96 weeks
Units: micromoles per liter (mcmol/L)
[All Cohorts] Change from baseline in protein, albumin, globulin and fibrinogen
时间窗: Up to 96 weeks
Units:grams per liter (g/L)
[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
时间窗: Up to 96 weeks
Units: millimoles per liter (mmol/L)
[All Cohorts] Change from baseline in Anion Gap
时间窗: Up to 96 weeks
Units: milliequivalents per liter (mEq/L)
[All Cohorts] Change from baseline in Estimated Glomerular Filtration Rate (eGFR)
时间窗: Up to 96 weeks
[All Cohorts] Change from baseline in Prothrombin Time and Partial Thromboplastin Time, Activated (APTT)
时间窗: Up to 96 weeks
[All Cohorts] Change from baseline in Prothrombin Time (INR)
时间窗: Up to 96 weeks
[All Cohorts] Change from baseline in urinalysis (Protein, glucose, ketones, blood, bilirubin, leucocyte esterase and nitrites
时间窗: Up to 96 weeks
Presence (positive, negative, trace) captured
[All Cohorts] Change from baseline in urinalysis (pH)
时间窗: Up to 96 weeks
[All Cohorts] Change from baseline in urinalysis (specific gravity)
时间窗: Up to 96 weeks
[All Cohorts] Number of participants experiencing treatment emergent adverse events
时间窗: Up to 164 weeks
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.
[All Cohorts] Changes from baseline in vital signs (heart rate)
时间窗: Up to 164 weeks
[All Cohorts] Changes from baseline in vital signs (systolic and diastolic blood pressure)
时间窗: Up to 164 weeks
[All Cohorts] Changes from baseline in vital signs (tympanic temperature)
时间窗: Up to 164 weeks
[All Cohorts] Changes from baseline in vital signs (respiratory rate)
时间窗: Up to 164 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
时间窗: Up to 164 weeks
All measured in 10x\^9L
[All Cohorts] Change from baseline in red blood cells
时间窗: Up to 164 weeks
Units x 10\^12L
[All Cohorts] Change from baseline in hemoglobin and mean corpuscular hemaglobin concentration
时间窗: Up to164 weeks
Units: grams per liter (g/L)
[All Cohorts] Change from baseline in mean corpuscular volume and mean platelet volume
时间窗: Up to 164 weeks
measured in femtoliter (fL)
[All Cohorts] Change from baseline in hematocrit
时间窗: Up to 164 weeks
Units: litres per litre (L/L)
[All Cohorts] Change from baseline in mean corpuscular hemoglobin
时间窗: Up to 164 weeks
Units: picograms (pg)
[All Cohorts] Change from baseline in neutrophils, lymphocytes, monocytes, eosinophils, basophils and reticulocyte count
时间窗: Up to 164 weeks
Units: %
[All Cohorts] Change from baseline in Alanine Transaminase, Alkaline Phosphatase, Aspartate aminotransferase, Creatine Phosphokinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase, Amylase and Lipase
时间窗: Up to 164 weeks
Units: units/Liter (U/L)
[All Cohorts] Change from baseline in Bilirubin (total, direct and indirect) and creatinine
时间窗: Up to 164 weeks
Units: micromoles per liter (mcmol/L)
[All Cohorts] Change from baseline in protein, albumin, globulin and fibrinogen
时间窗: Up to 164 weeks
Units:grams per liter (g/L)
[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
时间窗: Up to 164 weeks
Units: millimoles per liter (mmol/L)
[All Cohorts] Change from baseline in Anion Gap
时间窗: Up to 164 weeks
Units: milliequivalents per liter (mEq/L)
[All Cohorts] Change from baseline in Estimated Glomerular Filtration Rate (eGFR)
时间窗: Up to 164 weeks
[All Cohorts] Change from baseline in Prothrombin Time and Partial Thromboplastin Time, Activated (APTT)
时间窗: Up to 164 weeks
[All Cohorts] Change from baseline in Prothrombin Time (INR)
时间窗: Up to 164 weeks
[All Cohorts] Change from baseline in urinalysis (Protein, glucose, ketones, blood, bilirubin, leucocyte esterase and nitrites
时间窗: Up to 164 weeks
Presence (positive, negative, trace) captured
[All Cohorts] Change from baseline in urinalysis (pH)
时间窗: Up to 164 weeks
[All Cohorts] Change from baseline in urinalysis (specific gravity)
时间窗: Up to 164 weeks
(Cohort 1) Adverse Events
时间窗: 48 weeks
To evaluate the safety and tolerability of a single dose of IVT administered PYC-001 in participants with confirmed OPA1 mutation associated with ADOA. * Incidence, type, severity and relationship of ocular TEAEs, and treatment-emergent SAEs in the study eye at Week 4 (±7 days), Week 8 (±7 days), Week 24 (±2 weeks), and Week 48 (±2 weeks). * Incidence, type, severity and relationship of ocular TEAEs, and treatment-emergent SAEs in the fellow eye at Week 4 (±7 days), Week 8 (±7 days), Week 24 (±2 weeks), and Week 48 (±2 weeks). * Incidence, type, severity and relationship of non-ocular TEAEs, and treatment-emergent SAEs at Week 4 (±7 days), Week 8 (±7 days), Week 24 (±2 weeks), and Week 48 (±2 weeks).
(Cohort 1) Heart Rate change from baseline at Week 8/Week 48
时间窗: 8 / 48 Weeks
To evaluate the safety and tolerability of a single dose of IVT administered PYC-001 in participants with confirmed OPA1 mutation associated with ADOA.
(Cohort 1) Blood Pressure Change from baseline at Week 8/Week 48
时间窗: 8 Weeks/ 48 Weeks
To evaluate the safety and tolerability of a single dose of IVT administered PYC-001 in participants with confirmed OPA1 mutation associated with ADOA
(Cohort 1) Tympanic temperature change from baseline at Week 8/Week 48
时间窗: 8 weeks / 48 weeks
To evaluate the safety and tolerability of a single dose of IVT administered PYC-001 in participants with confirmed OPA1 mutation associated with ADOA
(Cohort 1) Respiratory rate change from baseline at Week 8 / Week 48
时间窗: 8 weeks / 48 weeks
To evaluate the safety and tolerability of a single dose of IVT administered PYC-001 in participants with confirmed OPA1 mutation associated with ADOA
(Cohort 1) Change from baseline for clinical laboratory results - hematology to Week 8 / Week 48
时间窗: 8 Weeks / 48 Weeks
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.
(Cohort 1) Change from baseline for clinical laboratory results - clinical chemistry to Week 8/Week 48
时间窗: 8 Weeks / 48 Weeks
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
(Cohort 1) Change in coagulation - Clinical laboratory results from baseline to Week 8/Week 48
时间窗: 8 Weeks / 48 Weeks
Coagulation screening parameters: Activated partial thromboplastin time, International normalized ratio/Prothrombin time, Fibrinogen
(Cohort 1) Change in urinalysis - Clinical laboratory results from baseline to Week 8/Week 48
时间窗: 8 Weeks / 48 Weeks
Urinalysis screening parameters: Bilirubin, Blood, Glucose, Ketones, Leukocyte esterase, Nitrites, pH, Protein, Specific gravity, Urobilinogen
(Repeat Dose Cohorts) Adverse Events
时间窗: 48 Weeks / 60 Weeks
To evaluate the safety and tolerability of multiple doses of intravitreally administered PYC-001 in participants with confirmed OPA1 mutation associated with ADOA. To determine optimal dose and dosing regimen for PYC-001. * Incidence, type, severity and relationship of ocular TEAEs, and treatment-emergent SAEs in the study eye over a 48-week (± 2 weeks) time period for 8-week dosing intervals Group, or a 60-week (± 2 weeks) time period for 12-week dosing intervals Group. * Incidence, type, severity and relationship of ocular TEAEs, and treatment-emergent SAEs in the fellow eye over a 48-week (± 2 weeks) time period for 8-week dosing intervals Group, or a 60-week (± 2 weeks) time period for 12-week dosing intervals Group. * Incidence, type, severity and relationship of non-ocular TEAEs, and treatment-emergent SAEs over a 48-week (± 2 weeks) time period for 8-week dosing intervals Group, or a 60-week (± 2 weeks) time period for 12-week dosing intervals group.
(Repeat Dose Cohorts) Heart Rate change from baseline at Week 48 / Week 60
时间窗: 48 Weeks / 60 Weeks
To evaluate the safety and tolerability of multiple doses of intravitreally administered PYC-001 in participants with confirmed OPA1 mutation associated with ADOA To determine optimal dose and dosing regimen for PYC-001. Week 48 for for 8-week dosing interval Group and Week 60 for 12-week dosing interval Group.
(Repeat Dose Cohorts) Blood Pressure Change from baseline at Week 48/ Week 60
时间窗: 48 Weeks / 60 Weeks
To evaluate the safety and tolerability of multiple doses of intravitreally administered PYC-001 in participants with confirmed OPA1 mutation associated with ADOA. To determine optimal dose and dosing regimen for PYC-001. Week 48 for 8-weeks dosing intervals Group Week 60 for 12-weeks dosing intervals Group
(Repeat Dose Cohorts) Tympanic Temperature Change from baseline at Week 48/ Week 60
时间窗: 48 Weeks / 60 Weeks
To evaluate the safety and tolerability of multiple doses of intravitreally administered PYC-001 in participants with confirmed OPA1 mutation associated with ADOA. To determine optimal dose and dosing regimen for PYC-001. Week 48 for 8-weeks dosing intervals Group Week 60 for 12-weeks dosing intervals Group
(Repeat Dose Cohorts) Respiratory Rate Change from baseline at Week 48/ Week 60
时间窗: 48 Weeks / 60 Weeks
To evaluate the safety and tolerability of multiple doses of intravitreally administered PYC-001 in participants with confirmed OPA1 mutation associated with ADOA. To determine optimal dose and dosing regimen for PYC-001. Week 48 for 8-weeks dosing intervals Group Week 60 for 12-weeks dosing intervals Group
(Repeat Dose Cohorts) Change in Clinical laboratory results - hematology from baseline at Week 48/ Week 60
时间窗: 48 Weeks / 60 Weeks
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. To determine optimal dose and dosing regimen for PYC-001. Week 48 for 8-weeks dosing intervals Group Week 60 for 12-weeks dosing intervals Group
(Repeat Dose Cohorts) Change in Clinical laboratory results - clinical chemistry from baseline at Week 48/ Week 60
时间窗: 48 Weeks / 60 Weeks
To evaluate the safety and tolerability of multiple doses of intravitreally administered PYC-001 in participants with confirmed OPA1 mutation associated with ADOA. To determine optimal dose and dosing regimen for PYC-001. Week 48 for 8-weeks dosing intervals Group Week 60 for 12-weeks dosing intervals Group
(Repeat Dose Cohorts) Change in Clinical laboratory results - coagulation from baseline at Week 48/ Week 60
时间窗: 48 Weeks / 60 Weeks
To evaluate the safety and tolerability of multiple doses of intravitreally administered PYC-001 in participants with confirmed OPA1 mutation associated with ADOA. To determine optimal dose and dosing regimen for PYC-001. Week 48 for 8-weeks dosing intervals Group Week 60 for 12-weeks dosing intervals Group
(Repeat Dose Cohorts) Change in Clinical laboratory results - urinalysis from baseline at Week 48/ Week 60
时间窗: 48 Weeks / 60 Weeks
To evaluate the safety and tolerability of multiple doses of intravitreally administered PYC-001 in participants with confirmed OPA1 mutation associated with ADOA. To determine optimal dose and dosing regimen for PYC-001. Week 48 for 8-weeks dosing intervals Group Week 60 for 12-weeks dosing intervals Group
次要结局
- [All Cohorts] Change from Baseline for Bruch's membrane opening (BMO) disc size, as determined by spectral domain optical coherence tomography(Up to 96 weeks)
- [All Cohorts] Change from Baseline in Mitochondrial function test via flavoprotein fluorescence(Up to 96 weeks)
- [Repeat Dose Cohorts] Plasma concentrations of PYC-001 following multiple dose intravitreally administered PYC-001(Up to 96 weeks)
- [All Cohorts] Change from Baseline for Ganglion Cell Layer (GCL) thickness determined by Spectral domain optical coherence tomography(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(Up to 96 weeks)
- [All Cohorts] Change from Baseline in Visual field sensitivity by photopic static perimetry(Up to 96 weeks)
- [All Cohorts] Change from Baseline in posterior eye health by fundus examination using ultrawide fundoscopy(Up to 96 weeks)
- [All Cohorts] Change from Baseline in Color vision(Up to 96 weeks)
- [All Cohorts] Change from Baseline in Contrast sensitivity by Pelli Robson chart(Up to 96 weeks)
- [All Cohorts] Change from Baseline in Multifocal visual evoked potential OR Full field electroretinogram(Up to 96 weeks)
- [All Cohorts] Change from Baseline in Retinal nerve fiber layer (RNFL) by spectral domain optical coherence tomography(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(Up to 164 weeks)
- [All Cohorts] Change from Baseline in Visual field sensitivity by photopic static perimetry(Up to 164 weeks)
- [All Cohorts] Change from Baseline in posterior eye health by fundus examination using ultrawide fundoscopy(Up to 164 weeks)
- [All Cohorts] Change from Baseline in Color vision(Up to 164 weeks)
- [All Cohorts] Change from Baseline in Contrast sensitivity by Pelli Robson chart(Up to 164 weeks)
- [All Cohorts] Change from Baseline in Multifocal visual evoked potential OR Full field electroretinogram(Up to 164 weeks)
- [All Cohorts] Change from Baseline in Retinal nerve fiber layer (RNFL) by spectral domain optical coherence tomography(Up to 164 weeks)
- [All Cohorts] Change from Baseline for Ganglion Cell Layer (GCL) thickness determined by Spectral domain optical coherence tomography(Up to 164 Weeks)
- [All Cohorts] Change from Baseline for Bruch's membrane opening (BMO) disc size, as determined by spectral domain optical coherence tomography(Up to 164 weeks)
- [All Cohorts] Change from Baseline in Mitochondrial function test via flavoprotein fluorescence(Up to 164 weeks)
- [Repeat Dose Cohorts] Plasma concentrations of PYC-001 following multiple dose intravitreally administered PYC-001(Up to 164 weeks)
- (Cohort 1) Change from Baseline for Multifocal visual evoked potential OR Full field electroretinogram(48 weeks)
- (Cohort 1) Change from Baseline for Best-corrected visual acuity letter score using Early Treatment of Diabetic Retinopathy Study(48 weeks)
- (Cohort 1) Change from Baseline for Low contrast visual acuity(48 weeks)
- (Cohort 1) Change from Baseline for High contrast visual acuity(48 weeks)
- (Cohort 1) Change from Baseline for Visual field sensitivity by photopic static perimetry(48 weeks)
- (Cohort 1) Change from Baseline for Posterior eye health by fundus examination, using ultrawide fundoscopy(48 weeks)
- (Cohort 1) Change from Baseline for Color vision by Hardy Rand Rittler test(48 weeks)
- (Cohort 1) Change from Baseline for Contrast sensitivity by Pelli Robson chart(48 weeks)
- (Cohort 1) Change from Baseline for Retinal nerve fiber layer (RNFL) by spectral domain optical coherence tomography(48 weeks)
- (Cohort 1) Change from Baseline for Mitochondrial function test by flavoprotein fluorescence analyzer (Ocumet Beacon)(48 weeks)
- (Repeat Dose Cohort) Change from Baseline for Best-corrected visual acuity letter score using Early Treatment of Diabetic Retinopathy Study(48 weeks / 60 Weeks)
- (Repeat Dose Cohort) Change from Baseline for Low contrast visual acuity(48 weeks / 60 Weeks)
- (Repeat Dose Cohort) Change from Baseline for High contrast visual acuity(48 weeks / 60 Weeks)
- (Repeat Dose Cohort) Change from Baseline for Visual field sensitivity by photopic static perimetry(48 weeks / 60 Weeks)
- (Repeat Dose Cohort) Change from Baseline for Posterior eye health by fundus examination, using ultrawide fundoscopy(48 weeks / 60 Weeks)
- (Repeat Dose Cohort) Change from Baseline for Color vision by Hardy Rand Rittler test(48 weeks / 60 Weeks)
- (Repeat Dose Cohort) Change from Baseline for Contrast sensitivity by Pelli Robson chart(48 weeks / 60 Weeks)
- (Repeat Dose Cohort) Change from Baseline for Multifocal visual evoked potential OR Full field electroretinogram(48 weeks / 60 Weeks)
- (Repeat Dose Cohort) Change from Baseline for Retinal nerve fiber layer (RNFL), by spectral domain optical coherence tomography(48 weeks / 60 Weeks)
- (Repeat Dose Cohort) Change from Baseline for Mitochondrial function test by flavoprotein fluorescence analyzer (Ocumet Beacon)(48 weeks / 60 Weeks)
- (Repeat Dose Cohort) Change from Baseline for Visual field using OLLEYES mobile device(48 weeks / 60 Weeks)
- (Repeat Dose Cohort) Plasma concentrations of PYC-001 following multiple dose intravitreally administered PYC-001(48 weeks / 60 Weeks)
- (Cohort 1) Change from Baseline for Ganglion Cell Layer (GCL) thickness determined by spectral domain optical coherence tomography(48 weeks)
- (Cohort 1) Change from Baseline for Bruch's membrane opening (BMO) disc size as determined by spectral domain optical coherence tomography(48 weeks)
- (Repeat Dose Cohort) Change from Baseline for Ganglion Cell Layer (GCL) thickness determined by Spectral domain optical coherence tomography(48 weeks / 60 Weeks)
- (Repeat Dose Cohort) Change from Baseline for Bruch's membrane opening (BMO) disc size, as determined by spectral domain optical coherence tomography(48 weeks / 60 Weeks)
- (Repeat Dose Cohort) Change from Baseline for visual acuity using OLLEYES mobile device(48 weeks / 60 Weeks)
- (Repeat Dose Cohort) Change from Baseline for contrast sensitivity using OLLEYES mobile device(48 weeks / 60 Weeks)
- (Repeat Dose Cohort) Change from Baseline for color vision using OLLEYES mobile device(48 weeks / 60 Weeks)