Safety, Tolerability and PK of Subcutaneous D-4517.2 in Subjects With Wet AMD or DME

NCT05387837 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: D-4517-002
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 16

Brief Summary

A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of D-4517.2 After Subcutaneous Administration in subjects with Neovascular (wet) Age-Related Macular Degeneration (AMD) or subjects with Diabetic Macular Edema (DME)

Conditions

Neovascular Age-related Macular Degeneration; Diabetic Macular Edema

Outcome Measures

Primary Outcomes (2)

• Stage 1 Safety Evaluation

  Safety of single dose of D-4517.2 as measured by Treatment-Emergent Adverse Events (TEAEs)

  12 weeks

• Stage 1A Safety Evaluation

  Safety of multiple SC doses of D-4517.2 as measured by Treatment-Emergent Adverse Events (TEAEs)

  40 Weeks

Secondary Outcomes (10)

• Stage 1: Number of participants with a reduction in sub-retinal fluid after a single intravitreal (IVT) dose of aflibercept and a single SC dose of D-4517.2

  Within subject, percent reduction in subretinal fluid volume in study eye after IVT aflibercept and D-4517.2 at 2, 4, 6, 8, and 12 weeks post-dose measured by spectral domain optical coherence tomography (SD-OCT).

• Stage 1: Number of participants with duration of effect of D-4517.2 as assessed by changes in subretinal fluid over time up to 12 weeks

  Within subject, central subfield thickness (CST) in study eye after IVT aflibercept and D-4517.2 at 2, 4, 6, 8, and 12 weeks post-dose as assessed by SD-OCT.

• Stage 1: Number of participants with Ocular and non-ocular adverse events (AEs) and serious adverse events (SAEs) observed for D-4517.2 and aflibercept

  By dose level, mean difference in percent reduction in subretinal fluid in study eye after IVT aflibercept and D-4517.2 at 2, 4, 6, 8, and 12 weeks post-dose as measured by SD-OCT.

• Stage 1: Number of participants with change in best corrected visual acuity (BCVA) in study eye after each treatment (aflibercept or D-4517.2).

  Change from baseline in BCVA in study eye as assessed by early treatment of diabetic retinopathy scale (ETDRS) after each treatment (aflibercept and D-4517.2) at 4, 6, 8, and 12 weeks post-dose.

• Stage 1A: Effect of different D-4517.2 dose regimens to maintain BCVA and CST following a single IVT aflibercept dose

  12 weeks of Aflibercept and 40 weeks of D-4517.2

Study Arms (4)

Stage 1 wAMD

EXPERIMENTAL

* Cohort A1 - 0.18 mg/kg of D-4517.2 * Cohort B1 - 0.36 mg/kg of D-4517.2 * Cohort C1 - 0.71 mg/kg of D-4517.2 * Cohort D1 - 1.5 mg/kg of D-4517.2

Drug: D-4517.2

Stage 1 DME

EXPERIMENTAL

* Cohort B2 - 0.36 mg/kg of D-4517.2 * Cohort C2 - 0.71 mg/kg of D-4517.2 * Cohort D2 - 1.5 mg/kg of D-4517.2

Drug: D-4517.2

Stage 1A wAMD

EXPERIMENTAL

* Cohort E1 - 2.0 mg/kg of D-4517.2 every 2 weeks * Cohort F1 - 2.0 mg/kg of D-4517.2 every 4 weeks

Drug: D-4517.2

Stage 1A DME

EXPERIMENTAL

* Cohort E2 - 2.0 mg/kg of D-4517.2 every 2 weeks * Cohort F2 - 2.0 mg/kg of D-4517.2 every 4 weeks

Drug: D-4517.2

Interventions

D-4517.2 DRUG

D-4517.2 (hydroxyl dendrimer VEGFR tyrosine kinase inhibitor)

Also known as: aflibercept

Stage 1 DME; Stage 1 wAMD; Stage 1A DME; Stage 1A wAMD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to give informed consent, comply with all study procedures, and be likely to complete the study.
• Demonstrated response to prior anti-VEGF treatment as defined by one or more of the following and as assessed by the Investigator for Stages 1 and 1A and confirmed by the Central Reader for Stage 2:
• Complete resolution or partial reduction of foveal intra- and/or subretinal fluid ≥ 30% from initial diagnosis as measured by SD-OCT.
• Increase in BCVA ≥ 2 lines from initial diagnosis using Snellen scale.
• Female subjects may be enrolled if they are:
• Not pregnant, lactating, or breastfeeding
• Documented in medical records or subject self-reported to be surgically sterile or postmenopausal.
• Female subjects of childbearing potential must practice true abstinence for at least 28 days prior to investigational product (IP) administration until 30 days after the last IP administration and have a negative serum and urine pregnancy test at Screening and Baseline Day 1, respectively, or
• Using 2 forms of highly effective contraception, including 1 physical barrier (condom or diaphragm) plus another method, such as adequate hormonal method (eg, contraceptive implants, injectables, or oral contraceptives) or nonhormonal methods (eg, intrauterine device or spermicidals) from Screening or at least 2 weeks prior to IP administration (whichever is earlier) until 30 days after the last IP administration and having a negative serum and urine pregnancy test at Screening and Baseline Day 1, respectively.
• Male subjects with female partners of childbearing potential may be enrolled if they are:
• Documented to be surgically sterile (vasectomy) in medical records or subject self-reported, or
• Agree to practice true abstinence during the study and for 30 days after the last IP administration, or
• Agree to use 2 adequate forms of highly effective contraception during the study, 1 of which should be a physical barrier for 30 days after the last IP administration.
• Must agree not to donate sperm during study and for 30 days following administration of the last dose of IP.
• Subjects who complete the Aflibercept Treatment Period in Stage 1 are eligible to enroll in Stage 1A if they meet all eligibility requirements. These subjects will enter the study in the D-4517.2 Treatment Period.

You may not qualify if:

• Medical Conditions:
• History, within 6 months prior to Screening, of any of the following: myocardial infarction, any cardiac event requiring hospitalization, treatment for acute congestive heart failure, transient ischemic attack or stroke.
• Uncontrolled hypertension with systolic BP ≥160 mmHg and/or diastolic BP ≥100 mmHg (while subject at rest) at the Screening Visit. If the subject's initial reading exceeds these values, a second reading may be taken 30 minutes later on the same day. If the subject's BP is controlled by antihypertensive medication, the subject should be taking the same medication continuously for at least 30 days prior to Day 1.
• Currently untreated diabetes mellitus, uncontrolled diabetes mellitus defined as HbA1c \> 12%, or previously untreated subjects with diabetes mellitus who initiated oral or injectable anti-diabetic medication within 3 months prior to Day 1.
• Chronic renal disease requiring chronic hemodialysis or renal transplantation.
• Abnormal liver function, as defined by transaminase or total bilirubin 2 times above the upper limit of normal at the Screening Visit.
• Medical history of Wolff-Parkinson-White Syndrome, family history of long QT or planned initiation or currently on medication prolonging QT time during the trial.
• Known allergy to constituents of the study drug formulation, aflibercept, or clinically relevant hypersensitivity to fluorescein used by the subject during the study.
• Serious systemic infections:
• Any active infections for which systemic anti-infectives were used within 4 weeks before Screening Visit.
• Recurrent or chronic infections or other active infections that, in the opinion of the Investigator, might cause this study to be detrimental to the subject.
• Any organic or psychiatric disorder, or laboratory abnormality which, in the opinion of the Investigator, will prevent the subject from completing the study activities as in the protocol or interfere with the interpretation of the study results.
• An underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious, or gastrointestinal) or history of other disease, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of study drug, might affect interpretation of the results of the study or which, in the opinion of the Investigator, renders the subject at unacceptable risk of treatment complications by participating in the trial.
• Any major illness or surgical procedure within 1 month before Screening.
• History of other diseases, physical examination finding, historical or current clinical laboratory finding giving reasonable suspicion of condition that contraindicates the use of the IP or that might affect the interpretation of the results of the study or renders the subject at high risk for treatment complications, in the opinion of the Investigator.

Sponsors & Collaborators

• Ashvattha Therapeutics, Inc.: lead

Study Sites (16)

Macro Trials

Los Angeles, California, 90026, United States

Location

University Retina - Lemont

Lemont, Illinois, 60439, United States

Location

Midwest Eye Institute - North

Indianapolis, Indiana, 46290, United States

Location

Cumberland Valley Retina Consultants

Hagerstown, Maryland, 21740, United States

Location

Ophthalmic Consultants of Boston

Boston, Massachusetts, 02114, United States

Location

Springield Clinic

Springfield, Missouri, 62794, United States

Location

The Retina Institute - Clayton Office

St Louis, Missouri, 63128, United States

Location

Envision Ocular, LLC

Bloomfield, New Jersey, 07003, United States

Location

Erie Retina Research

Eire, Pennsylvania, 16507, United States

Location

Texas Retina Associates - Arlington

Arlington, Texas, 76012, United States

Location

Austin Retina Associates

Austin, Texas, 78705, United States

Location

Medical Center Ophthalmology Associates - Northwest

San Antonio, Texas, 78240, United States

Location

Retinal Consultants of San Antonio

San Antonio, Texas, 78240, United States

Location

Strategic Clinical Research Group

Willow Park, Texas, 76087, United States

Location

Virginia Retina Center

Leesburg, Virginia, 20176, United States

Location

West Virginia University Eye Institute

Morgantown, West Virginia, 26505, United States

Location

MeSH Terms

Interventions

aflibercept

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2022
• First Posted: May 24, 2022
• Study Start: August 31, 2022
• Primary Completion: May 9, 2025
• Study Completion: September 30, 2025
• Last Updated: May 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)