Study to Evaluate the Safety of CG-P5 Peptide Eye Drops in Patients Diagnosed With Age-related Wet Macular Degeneration

Study Overview
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Brief Summary
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This will be a randomized, comparative, parallel, clinical study to assess initial safety and tolerability of CG-P5 peptide eye drops compared to placebo in patients diagnosed with age-related wet macular degeneration

Official Title
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Phase I Clinical Study to Evaluate the Safety of CG-P5 Peptide Eye Drops (Self-administered and Topically Applied) in Patients Diagnosed With Age-related Wet Macular Degeneration

Conditions
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Age-related Wet Macular Degeneration

Intervention / Treatment
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* Drug: CG-P5 peptide
* Drug: Placebo
* Drug: Aflibercept Injection [Eylea]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients ≥50 years of age Willing and able to provide written informed consent Diagnosis of age-related wet macular degeneration (wAMD) in the study eye as determined by the investigator on fundus examination Primary or recurrent active choroidal neovascularization (CNV) lesions involving the foveal center secondary to age-related wet macular degeneration in any one of the eyes. (If both eyes are affected and eligible, the eye with the worse BCVA, as assessed at screening, will be selected as the study eye Best corrected visual acuity (BCVA) of 75-25 eye Early Treatment of Diabetic Retinopathy Study (ETDRS) letters (approximate Snellen equivalent between 20/ 32 to 20/320) inclusive before pupil dilation assessed at the initial testing distance of 4 meters Central Subfield Thickness (CST thickness) ≥ 250 microns on SD-OCT (exclusive of subretinal pigment epithelial fluid, inclusive of SRF) Presence of SRF and/or IRF on SD-OCT Total lesion size not greater than 12 disc areas (30.48 mm2) (1 disc area = 2.54 mm2) on FA If present, subretinal hemorrhage must comprise < 50% of the total lesion area on FA, SD-OCT, or FAF No subfoveal fibrosis or atrophy on FA, SD-OCT, or FAF Active CNV membranes with subfoveal leakage or juxtafoveal leakage too close for laser photocoagulation Females who are of non-childbearing potential (surgically sterile or menopausal) OR if of childbearing potential using effective birth control and non-pregnant & non-lactating Ability to follow protocol requirements Exclusion Criteria: Patients having additional eye disease in the posterior segment of study eye other than wAMD Any other pathology involving the CNV lesion like retro foveolar atrophy or permanent structural damage to fovea or fibrosis/ hemorrhage involving fovea > 50 % of lesion area of study eye that can affect the efficacy of drug Vitreous hemorrhage or history of rhegmatogenous retinal detachment, retinal pigment epithelial tear involving the macula or macular hole (stage 3 or 4) in the study eye Aphakia or absence of the posterior capsule in the study eye History or expectation of the following surgery in the study eye: Vitrectomy within last 1 month Cataract surgery or Lasik within the last 3 months Planned cataract removal surgery during the study A history or medical diagnosis of uncontrolled glaucoma (defined as IOP >25mmHg even with anti-glaucoma medication), advanced glaucoma resulting in a cup/disc ratio >0.8 in the study eye, or glaucoma filtration surgery in the study eye Serious complications following surgery in the study eye within 1 year Current or planned use of medications known to be toxic to the retina, lens, or optic nerve (e.g., deferoxamine, chloroquine/hydro chloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol) Medical history or condition: Uncontrolled diabetes mellitus, with glycosylated hemoglobin (HbA1c) > 10%, myocardial infarction or stroke within 12 months of screening, active bleeding disorder, major surgery within 1 month of screening or when planned within the study period, hepatic impairment, uncontrolled hypertension, other unstable or progressive cardiovascular, pulmonary, Parkinson, liver, or renal disease or cancer or dementia Previous treatment with intravenous bevacizumab or intravitreal ranibizumab, bevacizumab, aflibercept, pegaptanib in either of the eyes within four months prior to enrolment Previous treatment with verteporfin photodynamic therapy (PDT), thermal laser, transpupillary thermotherapy, intravitreal or protein kinase C inhibitors or other AMD therapy in the study eye within 3 months prior to randomization Previous treatment with intravitreal ocular or periocular steroids (e.g., triamcinolone, anecortave acetate) or peribulbar steroid in the study eye within past 3 months Concurrent use of systemic anti-VEGF agents Any ophthalmic device implantation within the previous 12 months Patients with a clinically significant abnormal screening hematology, blood chemistry, or urinalysis, unsuitable for study participation in the investigator's opinion Aspartate Transaminase (AST), Alanine Transaminase (ALT), alkaline phosphatase, Gamma-glutamyl Transferase (GGT), total bilirubin, direct bilirubin, indirect bilirubin, and LDH ≥ 2.0-fold the upper limit of normal at screening Patient with impaired renal function defined as calculated creatinine clearance (CLCr) <30mL/min Males: CLCr = [140 - a(years)] x weight(kg)/ 72 x serum creatinine (mg/dL) Females: CLCr = [140 - a(years)] x weight(kg) (x 0.85)/ 72 x serum creatinine (mg/dL) Significant alcohol or drug abuse within past 2 years per investigator judgement Previous participation in other trials for treatment of wAMD with systemic administration if washout period from last administration is shorter than 3 months Significant disease or other medical conditions (as determined by medical history, examination, and clinical investigations at screening) that may, in the opinion of the investigator result in the any of the following: Put the patient at risk because of participation in the study, Influence the results of the study, Cause concern regarding the patient's ability to participate in the study Known hypersensitivity to fluorescein or any of the ingredients used in the study drug formulation, or any of the medications used during the study Active infectious conjunctivitis in either eye Women of childbearing potential who are lactating or who are pregnant as determined by serum pregnancy test at screening Women of childbearing potential must have agreed to use adequate birth control methods for the duration of the study Post-menopausal women should have documented last MC 2 years before study participation

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CG-P5 peptide eye drops<br> | Drug: CG-P5 peptide<br>* Patient will instill daily 1 package of CG-P5 peptide eye drops in the study eye [self-administered] using the single use tear-off disposable packaging<br>|
| Placebo Comparator: Placebo Eye drops<br> | Drug: Placebo<br>* Patient will instill daily 1 package of Placebo eye drops in the study eye [self-administered] using the single use tear-off disposable packaging<br>|
| Active Comparator: Intravitreal injection of Eylea®<br> | Drug: Aflibercept Injection [Eylea]<br>* Patient will receiver Eylea® (Aflibercept) intravitreal injection once in a month<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of occurrence of Adverse Events (AE) |  | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| The number of Adverse Events (AE) that occurs |  | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| Change in IOP with study drug compared to placebo | Mean change in intraocular pressure (IOP) with study drug compared to placebo from baseline to end of study | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| Change in intraocular inflammation with study drug compared to placebo | Mean change in intraocular inflammation with study drug compared to placebo from baseline to end of study | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| Incidence and severity of ocular and non-ocular adverse events of CG-P5 peptide eye drops and Placebo | Mean change in incidence and severity of ocular and non-ocular adverse events of CG-P5 peptide eye drops and Placebo with study drug compared to placebo from baseline to end of study | Day 0, Day 28, Day 56 & Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in best corrected visual acuity (BCVA) of study drug compared to Eylea® and placebo as measured by ≥15 Early ETDRS letter score at the end of 84 days |  | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| Change in CNV area on fluorescence angiography with study drug compared to Eylea® and placebo on day 28, day 56 and day 84 |  | Day 28, Day 56 & Day 84 | 
| Mean decrease in central retinal thickness on SD-OCT with study drug compared to Eylea® and placebo from baseline to end of study |  | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| Mean decrease in total macular volume on optical coherence tomography with study drug compared to Eylea® and placebo from baseline to end of study |  | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| Proportion of patients with change in BCVA with study drug compared to Eylea® and placebo from baseline to end of study |  | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| Number of patients with change in BCVA with study drug compared to Eylea® and placebo from baseline to end of study |  | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| Proportion of patients with change in intraocular pressure (IOP) with study drug compared to Eylea® and placebo from baseline to end of study |  | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| Number of patients with change in intraocular pressure (IOP) with study drug compared to Eylea® and placebo from baseline to end of study |  | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| Proportion of patients with change in intraocular inflammation with study drug compared to Eylea® and placebo from baseline to end of study |  | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| Number of patients with change in intraocular inflammation with study drug compared to Eylea® and placebo from baseline to end of study |  | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| Proportion of patients with change in central retinal thickness with study drug compared to Eylea® and placebo from baseline to end of study |  | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| Number of patients with change in central retinal thickness with study drug compared to Eylea® and placebo from baseline to end of study |  | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| Proportion of patients with change in total macular volume with study drug compared to Eylea® and placebo from baseline to end of study |  | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| Number of patients with change in total macular volume with study drug compared to Eylea® and placebo from baseline to end of study |  | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| Change from Baseline in Choroidal Neovascularization (CNV) area as measured by Fluorescein Angiography (FA) over the study duration |  | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| Change from Baseline in Central Subfield Thickness (CST) as measured by spectral domain optical coherence tomography (SD-OCT) over the study duration |  | Screening, Day 0, Day 28, Day 56 & Day 84 | 
| Area under the concentration-time curve from dosing (time 0) to time t [AUC(0-t)] | Pharmacokinetic profile of CG-P5 peptide eye drops measured by AUC(0-t) | Day 0 & Day 84 | 
| Maximum Plasma Concentration [Cmax] | Pharmacokinetic profile of CG-P5 peptide eye drops measured by Cmax | Day 0 & Day 84 | 
| Time of peak plasma concentration [Tmax] | Pharmacokinetic profile of CG-P5 peptide eye drops measured by Tmax | Day 0 & Day 84 | 
| Half-life [t½] | Pharmacokinetic profile of CG-P5 peptide eye drops measured by t½ | Day 0 & Day 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Age-Related Macular Degeneration, Macular Degeneration, wAMD