A Safety Study of KHK4951 in Healthy Volunteers and Patients With Wet Age-Related Macular Degeneration

Study Overview
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Brief Summary
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The purpose of this study is to evaluate safety and tolerability after administration of KHK4951 in healthy volunteers and patients with wet age-related macular degeneration.

Official Title
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A Phase I Study of KHK4951 in Healthy Volunteers and Patients With Wet Age-Related Macular Degeneration

Conditions
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Healthy Volunteers, Wet Age-related Macular Degeneration

Intervention / Treatment
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* Drug: Placebo
* Drug: KHK4951


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Volunteers Voluntary written informed consent to participate in the study Japanese or white men 20 to < 50 years at the time of informed consent BMI 18.5 to < 30.0 at screening Intraocular pressure (study eye) 10.0 mm Hg to 21.0 mm Hg Monocular or binocular visual acuity (corrected visual acuity if correction is required) ≥ 1.0 at screening Inclusion Criteria: Patients Voluntary written informed consent to participate in the study Age ≥ 50 years at the time of informed consent AMD-associated by active subfoveal CNV lesions in the study eye or juxtafoveal CNV lesions with CNV-associated findings in the fovea in the study eye CST ≥ 300 μm in the study eye at screening, as measured by OCT BCVA score ≥ 23 letters in the study eye at screening and enrollment, as measured by the ETDRS visual acuity chart BCVA score ≥ 58 letters in the non-study eye at screening, as measured by the ETDRS visual acuity chart In subjects with prior treatment of the study eye with anti-vascular endothelial growth factor (anti-VEGF) drugs such as Beovu, Eylea, Lucentis, Avastin, or Macugen, presence of response to the anti-VEGF drug(s) as judged by the investigator or subinvestigator based OCT, FA, visual acuity, or other assessment results Exclusion Criteria: Healthy Volunteers Current illness requiring treatment History of ophthalmologic laser surgery, ophthalmologic surgery, nasolacrimal duct surgery, orany eyelid surgery affecting flow in the nasolacrimal duct History of or current circulatory disease (e.g., cerebrovascular or cardiovascular disease) History of or current dry eye Abnormal findings on OCT at screening or enrollment examination Exclusion Criteria: Patients Clinical findings or a history of conditions other than wAMD affecting the retina and choroid (e.g., diabetic retinopathy, diabetic macular edema, myopic CNV, retinal vein occlusion, or premacular membrane) in either of the eyes Any of the following diseases in the study eye: Glaucoma Ischemic optic neuropathy Retinitis pigmentosa Current or history of vitreous hemorrhage or macular hole in the study eye Any abnormality in the anterior segment of the eye or vitreous body that may affect fundus observation by OCT, color fundus photography, or fluorescein angiography

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo is administered once daily or three times daily.<br>|
| Experimental: KHK4951<br> | Drug: KHK4951<br>* KHK4951 is administered once daily or three times daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | For adverse events that occurred after administration of the investigational drug, number of subjects with AEs and occurrence frequency are evaluated. | Day 1 to Day 43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum KHK4951 concentration |  | Healthy Volunteers: Day 1, Day2, Day4, Day8, Day12, Day16, Day21, Day23, Day 25, Day 29, Day 36, Day 43; Patients: Day 1, 8, 22, 43 | 
| Time to the maximum concentration |  | Day 1 to Day 43 | 
| The maximum concentration |  | Day 1 to Day 43 | 
| Area under the concentration-time curve |  | Day 1 to Day 43 | 
| Apparent clearance |  | Day 1 to Day 43 | 
| Elimination half-life |  | Day 1 to Day 43 |