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

Running, not enrolling · Phase 2

Conditions studied: Neovascular Age-related Macular Degeneration, Diabetic Macular Edema

In brief

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)

Key facts

Study ID

NCT05387837

Run by

Ashvattha Therapeutics, Inc.

People needed

50

Starts

2022-08-31

Expected to finish

2025-09-30

Last updated by the study team

2025-05-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Overall Study Inclusion Criteria-For All Subjects:
• 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.
• Subjects who complete Stage 1 and/or Stage 1A are eligible to enroll in Stage 2 if they meet all eligibility requirements.
• Ocular media clarity, pupillary dilation and individual cooperation sufficient for adequate fundus imaging in the opinion of the Investigator.
• Recurrence of intra- or subretinal fluid at study Baseline. This inclusion criterion will be confirmed by the Sponsor or Central Reader in Stages 1 and 1A and by the Central Reader in Stage 2.
• For subjects with bilateral disease, only one eye per subject can participate in the study. In cases where both eyes are eligible, the eye with the worse BCVA at the Screening Visit will be selected as the study eye. If both eyes have the same BCVA, the eye with the largest CST will be selected as the study eye.
• Subjects With wAMD (For all Stages):
• Male or nonpregnant female adults aged ≥50 years at time of signing the informed consent form (ICF).
• BCVA letter score between 75 and 23 letters (ETDRS chart) (20/32 to 20/320 Snellen equivalents) inclusive in the study eye at Baseline and BCVA letter score of at least 35 letters (ETDRS chart) (20/200 Snellen equivalent) in the non-study eye.
• Previously treated subjects with at least 3 prior IVT injections with an anti-VEGF agent (aflibercept, bevacizumab, faricimab, ranibizumab, or any other approved anti-VEGF agent) with last treatment administered between 4 and 12 weeks prior to Screening. Administration of IVT anti-VEGF agents prior to enrollment must not be more than 12 weeks apart. This inclusion criterion will be assessed by the Investigator.
• For Stage 2, presence of a choroidal neovascular (CNV) lesion secondary to wAMD confirmed by the Central Reader.

You may not qualify if…

• A subject who meets any of the following exclusion criteria will not be eligible for inclusion in the study:
• 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.
• Positive screen antibodies for hepatitis B or hepatitis C virus subsequently confirmed to suggest active infection, or HIV type 1 or 2 antibodies.
• Prior/Concomitant Therapy:
• Participation in any investigational study within 30 days prior to Screening, or planned use of an IP or device during the study; any exposure to a prior investigational drug product must be fully washed out (at least 5 half-lives).
• Chronic alcohol or drug abuse or any condition that, in the Investigator's opinion, makes them an unreliable study participant or unlikely to complete the trial.
• Use of systemic medications known to be toxic to the lens, retina or optic nerve (eg, deferoxamine, chloroquine/hydroxy-chloroquine, tamoxifen, phenothiazines, and ethambutol) used during the 6 month or 5 half-lives (whichever is longer) prior to Day 1 or likely need to be used.
• Use of systemic immunomodulatory treatments (eg, interleukin-6 inhibitors) within 6 months or 5 half-lives (whichever is longer) prior to Day 1.
• Use of systemic corticosteroids (ie, oral, IM, IV, intranasal) within 1 month prior to Day 1 and no corticosteroids anticipated throughout the trial.
• Systemic treatment for suspected or active systemic infections.
• Administration of systemic anti-VEGF or pro-VEGF treatment within 180 days or 5 half-lives, whichever is longer, before Screening Visit.

Where it is running

• Macro Trials — Los Angeles, California, United States
• University Retina - Lemont — Lemont, Illinois, United States
• Midwest Eye Institute - North — Indianapolis, Indiana, United States
• Cumberland Valley Retina Consultants — Hagerstown, Maryland, United States
• Ophthalmic Consultants of Boston — Boston, Massachusetts, United States
• Springield Clinic — Springfield, Missouri, United States
• The Retina Institute - Clayton Office — St Louis, Missouri, United States
• Envision Ocular, LLC — Bloomfield, New Jersey, United States
• Erie Retina Research — Eire, Pennsylvania, United States
• Texas Retina Associates - Arlington — Arlington, Texas, United States
• Austin Retina Associates — Austin, Texas, United States
• Medical Center Ophthalmology Associates - Northwest — San Antonio, Texas, United States
• Retinal Consultants of San Antonio — San Antonio, Texas, United States
• Strategic Clinical Research Group — Willow Park, Texas, United States
• Virginia Retina Center — Leesburg, Virginia, United States
• West Virginia University Eye Institute — Morgantown, West Virginia, United States

Full record on ClinicalTrials.gov

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