A Study Assessing AR-13503 Implant Alone and in Combination With Aflibercept in Subjects With nAMD or DME

• ClinicalTrials.gov Identifier: NCT03835884
• Recruitment Status: Recruiting
• First Posted: February 11, 2019
• Last Update Posted: August 27, 2019
• Sponsor: Aerie Pharmaceuticals
• Information provided by (Responsible Party): Aerie Pharmaceuticals

Study Description

Brief Summary:

First-in-Human Study of the Safety of AR-13503 Sustained Release Intravitreal Implant in Subjects with Neovascular Age-Related Macular Degeneration (nAMD) and Subjects with Diabetic Macular Edema (DME)

Condition or disease	Intervention/treatment	Phase
Neovascular Age-related Macular Degeneration; Diabetic Macular Edema	Drug: AR-13503 Implant Low Dose; Drug: AR-13503 Implant High Dose; Drug: Aflibercept; Other: Sham	Phase 1

Detailed Description:

This is a first-in-human 24-week study conducted in 2 sequential stages. Stage 1 is a multicenter, open label study of the safety and tolerability of a single intravitreal administration of AR-13503 SR Implant in escalating doses and Stage 2 is a multicenter, single masked, randomized, parallel group study of the safety and preliminary response of AR-13503 SR Implant alone and in combination with aflibercept compared with aflibercept alone.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Single (Participant)
• Masking Description: No masking (stage 1) and participant (Stage 2)
• Primary Purpose: Treatment
• Official Title: First-in-Human Study of the Safety of AR-13503 Sustained Release Intravitreal Implant in Subjects With Neovascular Age-Related Macular Degeneration (nAMD) and Subjects With Diabetic Macular Edema (DME)
• Actual Study Start Date: August 16, 2019
• Estimated Primary Completion Date: September 2021
• Estimated Study Completion Date: September 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: AR-13503 Implant Low Dose; Single dose of AR-13503 Implant Low Dose (10.6 µg) administered as an intravitreal implant into a single eye of up to 6 subjects (3 nAMD and 3 DME) who will be followed for 24 weeks	Drug: AR-13503 Implant Low Dose; AR-13503 Implant Low Dose (10.6 µg) administered as an intravitreal implant into a single eye
Experimental: AR-13503 Implant High Dose; Single dose of AR-13503 Implant High Dose (21.2 µg) administered as an intravitreal implant into a single eye of up to 6 subjects (3 nAMD and 3 DME) who will be followed for 24 weeks	Drug: AR-13503 Implant High Dose; AR-13503 Implant High Dose (21.2 µg) administered as an intravitreal implant into a single eye
Experimental: AR-13503 Implant Low Dose + Aflibercept; Single dose of AR-13503 Implant Low Dose (10.6 µg) administered as an intravitreal implant plus intravitreal injections of aflibercept into a single eye of up to 18 subjects (9 nAMD and 9 DME) who will be followed for 24 weeks	Drug: AR-13503 Implant Low Dose; AR-13503 Implant Low Dose (10.6 µg) administered as an intravitreal implant into a single eye; Drug: Aflibercept; Intravitreal Injection
Experimental: AR-13503 Implant High Dose + Aflibercept; Single dose of AR-13503 Implant High Dose (21.2 µg) administered as an intravitreal implant plus intravitreal injections of aflibercept into a single eye of up to 18 subjects (9 nAMD and 9 DME) who will be followed for 24 weeks	Drug: AR-13503 Implant High Dose; AR-13503 Implant High Dose (21.2 µg) administered as an intravitreal implant into a single eye; Drug: Aflibercept; Intravitreal Injection
Experimental: AR-13503 Implant Low Dose + sham; Single dose of AR-13503 Implant Low Dose (10.6 µg) administered as an intravitreal implant plus sham injections (touch eye only; no injection) into a single eye of up to 18 subjects (9 nAMD and 9 DME)who will be followed for 24 weeks	Drug: AR-13503 Implant Low Dose; AR-13503 Implant Low Dose (10.6 µg) administered as an intravitreal implant into a single eye; Other: Sham; Sham injection (Touch eye only; no injection)
Experimental: AR-13503 Implant High Dose + sham; Single dose of AR-13503 Implant High Dose (21.2 µg) administered as an intravitreal implant plus sham injections (touch eye only; no injection) into a single eye of up to 18 subjects (9 nAMD and 9 DME) who will be followed for 24 weeks	Drug: AR-13503 Implant High Dose; AR-13503 Implant High Dose (21.2 µg) administered as an intravitreal implant into a single eye; Other: Sham; Sham injection (Touch eye only; no injection)
Experimental: Sham + Aflibercept; Sham injection (touch eye only; no injection) plus intravitreal injections of Aflibercept into a single eye of up to 18 subjects (9 nAMD and 9 DME) who will be followed for 24 weeks	Drug: Aflibercept; Intravitreal Injection; Other: Sham; Sham injection (Touch eye only; no injection)

Outcome Measures

Primary Outcome Measures :

1. Number of ocular and non-ocular TEAEs [ Time Frame: 24 weeks ]
   Number of ocular and non-ocular treatment-emergent adverse events (TEAEs), summarized at the subject level by system organ class and preferred term, and also by severity and relatedness to treatment.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria for Subjects with Neovascular Age-Related Macular Degeneration (nAMD) or Diabetic Macular Edema (DME)

1. 50 years of age or older
2. Presence of active subfoveal or juxtafoveal Choroidal Neovascularization (CNV) (any subtype) with leakage affecting the fovea secondary to Age-Related Macular Degeneration (AMD)

3. Best Corrected Visual Acuity (BCVA) in the study eye at Baseline (Day 0):

   Stage 1: between 65 and 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/50 and 20/640 Snellen equivalent) Stage 2: between 65 and 20 ETDRS letters (20/50 and 20/400 Snellen equivalent)

4. Able and willing to give signed informed consent and follow study instructions

Inclusion Criteria for Subjects with DME

Subjects with Diabetic Macular Edema (DME) must meet all the following criteria to enter into the study:

1. 18 years of age or older
2. Type 1 or 2 diabetes mellitus with center-involved DME

3. BCVA in the study eye at Baseline (Day 0):

   Stage 1: between 65 and 10 ETDRS letters (20/50 and 20/640 Snellen equivalent) Stage 2: between 65 and 20 ETDRS letters (20/50 and 20/400 Snellen equivalent)

4. Able and willing to give signed informed consent and follow study instructions

Exclusion Criteria for Subjects with Neovascular Age-Related Macular Degeneration (nAMD)

Ophthalmic:

1. Use of intravitreal aflibercept within 8 weeks, ranibizumab or bevacizumab within 6 weeks
2. History of vitreoretinal surgery in the study eye
3. Any ocular disease in the study eye that in the Investigator and Reading Center's opinion may confound assessment of the macula, affect central vision, confound results, or preclude improvement in visual acuity
4. Any current or history of periocular or intraocular inflammation or evidence of infection in either eye
5. Media clarity insufficient to obtain quality fundus and OCT images in the study eye

Systemic:

1. History or current systemic condition that in the Investigator opinion preclude the safe administration of the study treatment or confound results
2. History of allergy or sensitivity to fluorescein or povidone iodine
3. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control
4. Participation in an investigational study within 30 days of Screening

Exclusion Criteria for Subjects with DME

Ophthalmic:

1. Use of intraocular or periocular corticosteroids within 6 months, aflibercept within 8 weeks, ranibizumab or bevacizumab within 6 weeks
2. History of vitreoretinal surgery in the study eye
3. High risk proliferative diabetic retinopathy in the study eye and related complications
4. Structural damage to the center or the macula that is likely to preclude improvement in visual acuity in the study eye after resolution of the DME
5. Media clarity insufficient to obtain quality fundus and OCT images in the study eye

Systemic:

1. History or current medical condition that in the Investigator's opinion preclude the safe administration of the study treatment or confound results
2. History of allergy or sensitivity to fluorescein or povidone iodine
3. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control
4. Participation in an investigational study within 30 days of Screening

Contacts and Locations

Contacts

Contact: Nancy Ramirez, MS; 8885945111; nramirez@aeriepharma.com

Contact: Puiwah Braswell; 8885945111; pbraswell@aeriepharma.com

Locations

United States, Arizona

Retinal Research Institute, LLC; Not yet recruiting

Gilbert, Arizona, United States, 85296

Arizona Retina & Vitreous Consultants; Not yet recruiting

Phoenix, Arizona, United States, 85021

United States, California

Retina-Vitreous Associates Medical Group; Recruiting

Beverly Hills, California, United States, 90211

Byers Eye Institute; Not yet recruiting

Palo Alto, California, United States, 94303

Doheny Eye Center, UCLA; Not yet recruiting

Pasadena, California, United States, 91105

Retina Consultants San Diego; Not yet recruiting

Poway, California, United States, 92064

Bay Area Retina Associates; Not yet recruiting

Walnut Creek, California, United States, 94598

United States, Florida

Florida Eye Clinic; Recruiting

Altamonte Springs, Florida, United States, 32701

Retina Vitreous Associates of Florida; Not yet recruiting

Saint Petersburg, Florida, United States, 33711

Southern Vitreoretinal Associates, P.L.; Not yet recruiting

Tallahassee, Florida, United States, 32308

United States, New Jersey

Mid Atlantic Retina; Not yet recruiting

Cherry Hill, New Jersey, United States, 08034

United States, North Carolina

Duke Eye Center; Not yet recruiting

Durham, North Carolina, United States, 27705

United States, Ohio

Sterling Research Group, Ltd.; Not yet recruiting

Cincinnati, Ohio, United States, 45219

Cleveland Clinic, Cole Eye Institute; Not yet recruiting

Cleveland, Ohio, United States, 44195

United States, Oregon

Retina & Vitreous Center of Southern Oregon PM; Recruiting

Ashland, Oregon, United States, 97520

Oregon Retina, LLP; Recruiting

Eugene, Oregon, United States, 97401

Retina Northwest, P.C.; Recruiting

Portland, Oregon, United States, 97221

United States, Pennsylvania

Mid Atlantic Retina; Not yet recruiting

Huntingdon Valley, Pennsylvania, United States, 19006

United States, Texas

Valley Retina Institute, P.A.; Recruiting

Harlingen, Texas, United States, 78550

Medical Center Ophthamology Associates; Recruiting

San Antonio, Texas, United States, 78240

Sponsors and Collaborators

Aerie Pharmaceuticals

Investigators

• Study Director: Mark Herring; Aerie Pharmaceuticals, Inc.

More Information

• Responsible Party: Aerie Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03835884 History of Changes
• Other Study ID Numbers: AR-13503-CS201
• First Posted: February 11, 2019
• Last Update Posted: August 27, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Aerie Pharmaceuticals:

Neovascular AMD; Diabetic macular edema; Diabetic retinopathy; Vascular endothelial growth factor; Intravitreal injection

Additional relevant MeSH terms:

Macular Degeneration; Macular Edema; Wet Macular Degeneration; Edema; Signs and Symptoms; Retinal Degeneration; Retinal Diseases; Eye Diseases