CLN-0046: Treatment of AMD Subjects With OTX-TKI

Study Overview
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Brief Summary
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To evaluate the safety, tolerability and efficacy of OTX-TKI for intravitreal use, in subjects who have neovascular age-related macular degeneration (AMD).

Detailed Description
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A multi-center, dose escalation, Phase 1, safety, tolerability and efficacy study to evaluate three dose groups of the OTX-TKI implant to treat subjects with a diagnosis of primary subfoveal neovascularization secondary to AMD.

Official Title
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A Phase 1 Open-Label, Dose Escalation Study of OTX-TKI for Intravitreal Use in Subjects With Neovascular Age-Related Macular Degeneration (AMD)

Conditions
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Neovascular Age-related Macular Degeneration

Intervention / Treatment
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* Drug: OTX-TKI
* Drug: OTX-TKI
* Drug: OTX-TKI
* Drug: OTX-TKI
* Drug: Anti-VEGF
* Drug: OTX-TKI
* Drug: Anti-VEGF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are at least 50 years of age Are eligible for standard therapy Have active primary CNVM secondary to AMD, either newly diagnosed or previously treated with documented response to anti-VEGF therapy in the study eye [primary subfoveal CNV secondary to AMD including juxtafoveal lesions that affect the fovea] documented by FA and SD-OCT Are female who is postmenopausal for at least 12 months prior to screening or surgically sterile; or male or female of childbearing potential willing to use two forms of adequate contraception Are able and willing to comply with all study requirements and visits Exclusion Criteria: Have previous laser photocoagulation to the center of the fovea in the study eye Have participated in any study involving an investigational drug either in the U.S. or outside the U.S. within the past 30 days Are an employee of the site that is directly involved in the management, administration, or support of the study, or be an immediate family member of the same Have a presence of a disease other than CNVM due to AMD in the study eye that could affect vision or safety assessments

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 100 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (Low Dose)<br>Subjects will receive a low dose of OTX-TKI | Drug: OTX-TKI<br>* OTX-TKI is a dried polyethylene glycol-based hydrogel fiber containing dispersed microcrystals of a small molecule tyrosine kinase inhibitor (TKI).<br>|
| Experimental: Cohort 2 (Middle Dose)<br>Subjects will receive a middle dose of OTX-TKI. | Drug: OTX-TKI<br>* OTX-TKI is a dried polyethylene glycol-based hydrogel fiber containing dispersed microcrystals of a small molecule tyrosine kinase inhibitor (TKI).<br>|
| Experimental: Cohort 3 (High Dose)<br>Subjects will receive a high dose of OTX-TKI. | Drug: OTX-TKI<br>* OTX-TKI is a dried polyethylene glycol-based hydrogel fiber containing dispersed microcrystals of a small molecule tyrosine kinase inhibitor (TKI).<br>|
| Experimental: Cohort 3 (Anti-VEGF)<br>Subjects will receive OTX-TKI plus a single anti-VEGF injection | Drug: OTX-TKI<br>* OTX-TKI is a dried polyethylene glycol-based hydrogel fiber containing dispersed microcrystals of a small molecule tyrosine kinase inhibitor (TKI).<br>Drug: Anti-VEGF<br>* Standard of care therapy used to block vascular endothelial growth factor<br>* Other names: ranibizumab;|
| Experimental: Cohort 4 (High Dose)<br>Subjects will receive a high dose of OTX-TKI. | Drug: OTX-TKI<br>* OTX-TKI is a dried polyethylene glycol-based hydrogel fiber containing dispersed microcrystals of a small molecule tyrosine kinase inhibitor (TKI).<br>|
| Experimental: Cohort 4 (Anti-VEGF)<br>Subjects will receive OTX-TKI plus a single anti-VEGF injection | Drug: OTX-TKI<br>* OTX-TKI is a dried polyethylene glycol-based hydrogel fiber containing dispersed microcrystals of a small molecule tyrosine kinase inhibitor (TKI).<br>Drug: Anti-VEGF<br>* Standard of care therapy used to block vascular endothelial growth factor<br>* Other names: ranibizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events for each subject | All adverse events from screening through end of study will be captured | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the Maximum Tolerated Dose of the OTX-TKI injection | A Central Reading Center will evaluate multiple imaging modalities to confirm evidence of biological activity for subjects that have been treated with the OTX-TKI injection. If all subjects tolerate lower dosages, additional subjects will be treated at higher dosages. All data will be evaluated by the DSMC who, in concert with the Medical Monitor, will determine the Maximally Tolerated Dose. | 9 months |