D-4517.2 for Age-Related Macular Degeneration and Diabetic Macular Edema

(Tejas Trial)

Not currently recruiting at 18 trial locations

Overseen By Jenni Herber

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ashvattha Therapeutics, Inc.

Must be taking: Anti-VEGF agents

Must not be taking: Systemic corticosteroids, Immunomodulatory treatments

Disqualifiers: Cardiac events, Uncontrolled hypertension, Chronic renal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, D-4517.2, for individuals with wet age-related macular degeneration (AMD) and diabetic macular edema (DME). The researchers aim to determine the treatment's safety and how the body processes it after subcutaneous injection. Participants will receive varying doses to identify the most effective and safest option. This trial may suit those who have had wet AMD or DME, responded to previous treatments, and currently experience vision issues due to these conditions. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use certain medications like systemic corticosteroids or those toxic to the eye during the trial. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that D-4517.2 is likely to be safe for humans?

Research has shown that D-4517.2 is safe and well-tolerated in healthy individuals. In earlier studies, participants received single doses through subcutaneous injection, which did not cause any serious side effects. This suggests the treatment might be safe for further testing in individuals with eye conditions such as wet age-related macular degeneration (AMD) and diabetic macular edema (DME). Since these studies involved healthy individuals, additional research in those with these eye conditions will help confirm its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for AMD and DME?

Researchers are excited about D-4517.2 because it offers a potentially new approach to treating age-related macular degeneration (wAMD) and diabetic macular edema (DME). Unlike current treatments, which often involve repeated eye injections of anti-VEGF drugs, D-4517.2 is administered in varying dosages and frequencies, potentially reducing the treatment burden. It's being tested in different cohorts, some receiving higher doses or more frequent administration, which might enhance effectiveness and convenience. This flexibility in dosing could lead to a more tailored treatment experience for patients, possibly improving outcomes and patient adherence.

What evidence suggests that D-4517.2 might be an effective treatment for age-related macular degeneration and diabetic macular edema?

Research has shown that D-4517.2 may help treat wet age-related macular degeneration (AMD) and diabetic macular edema (DME). This trial will evaluate different dosages and schedules of D-4517.2 for these conditions. Studies have found that patients using this treatment experienced improvements in eye structure and vision, key indicators of better eye health. Additionally, D-4517.2 may reduce the need for frequent injections, offering a more convenient option for patients. Early studies also suggest it could be a safe and effective medication for these eye conditions. These findings indicate that D-4517.2 might be a good treatment choice for people with wet AMD and DME. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with wet Age-Related Macular Degeneration (AMD) or Diabetic Macular Edema (DME). Participants must have shown improvement after previous anti-VEGF treatments, agree to contraception if of childbearing potential, and be likely to complete the study. Exclusions include uncontrolled blood pressure or diabetes, certain allergies, recent heart attacks or strokes, and other serious health conditions.

Inclusion Criteria

The doctor will check if you meet these requirements in the first stage of the study.

You agree to not have sexual intercourse during the study and 30 days after the last dose of the study drug OR you agree to use two reliable forms of birth control during the study, including at least one physical barrier method, for 30 days after the last dose of the study drug.

You cannot donate sperm for a month after finishing the study.

Exclusion Criteria

Must have no history of Treatment of either DME or DR with macular laser

Patients with uncontrolled high blood pressure and/or diabetes will not be eligible.

Known allergy to constituents of the study drug formulation, Aflibercept, or clinically relevant hypersensitivity to fluorescein used by the patient during the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1: Single Dose Treatment

Single subcutaneous dose open-label assessment of safety and pharmacodynamic response to D-4517.2 in subjects with wAMD or DME

12 weeks

Visits at 2, 4, 6, 8, and 12 weeks post-dose

Stage 1A: Multiple Dose Treatment

Multiple subcutaneous dose open-label assessment of safety, pharmacokinetics, and pharmacodynamic response to D-4517.2 co-administered with Aflibercept in subjects with wAMD and DME

40 weeks

Regular visits every 2 or 4 weeks depending on cohort

Stage 2: Randomized Controlled Study

Visual examiner-masked, randomized active, sham, and placebo-controlled study evaluating the safety, tolerability, pharmacokinetics, and efficacy of subcutaneously administered D-4517.2 to subjects with wAMD

Not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• D-4517.2

Trial Overview The trial tests a new medication called D-4517.2 administered under the skin for people with wet AMD or DME. It aims to evaluate safety, how well it's tolerated by patients, and how the body processes it.

How Is the Trial Designed?

Group I: Stage 1A wAMD Experimental Treatment 1 Intervention

* 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

Group II: Stage 1A DME Experimental Treatment 1 Intervention

* 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

Group III: Stage 1 wAMD Experimental Treatment 1 Intervention

* 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

Group IV: Stage 1 DME Experimental Treatment 1 Intervention

* 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

Who Is Running the Clinical Trial?

Ashvattha Therapeutics, Inc.

Lead Sponsor

Trials

4

Recruited

160+

Published Research Related to This Trial

In a study involving 36 treatment-naïve patients with neovascular age-related macular degeneration (nAMD), intravitreal aflibercept injections led to a significant decrease in macular ganglion cell complex (GCC) thickness over 12 months.

The reduction in GCC thickness, particularly in the ganglion cell layer, suggests that while aflibercept is used to treat nAMD, it may also impact the structural integrity of the retina, indicating a need for careful monitoring of retinal health in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Macular ganglion cell complex changes in eyes treated with aflibercept for neovascular age-related macular degeneration. Aşikgarip, N., Temel, E., Örnek, K.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05387837

Study Details | NCT05387837 | Safety, Tolerability and PK ... A study to evaluate the safety, tolerability and pharmacokinetics of D-4517.2 after subcutaneous administration in subjects with neovascular (wet) age-related ...

2. retinalphysician.com retinalphysician.com/issues/2025/september/euretina6/

Migaldendranib Demonstrates Efficacy in DME and nAMD Phase 2 results presented at Euretina showed reduced injection frequency as well as improvements in retinal structure and visual function.

3. avttx.com avttx.com/ashvattha-therapeutics-announces-first-patient-dosed-via-subcutaneous-administration-of-anti-angiogenic-therapeutic-d-4517-2-for-wet-amd-and-dme-in-phase-2-chronic-dosing-study/

Ashvattha Therapeutics Announces First Patient Dosed via ... The open-label study will evaluate the safety and efficacy of chronic D-4517.2 dosing in patients with wet AMD and DME. “This study marks a ...

4. retinatoday.com retinatoday.com/articles/2024-nov-dec/the-therapeutic-landscape-for-diabetic-eye-disease

The Therapeutic Landscape for Diabetic Eye Disease The phase 2 study (NCT05387837) is evaluating the safety, tolerability, pharmacokinetics, and efficacy of various dosages of D-4517.2 in patients with wet AMD ...

5. iovs.arvojournals.org iovs.arvojournals.org/article.aspx?articleid=2786516

Oral Formulation Development of the Anti-Angiogenesis Drug ... These preclinical studies support the development of D-4517.2 as a potential safe and effective oral agent that can be administered chronically to wet AMD and ...

6. avttx.com avttx.com/ashvattha-therapeutics-presents-phase-1-safety-data-in-healthy-subjects-for-subcutaneous-anti-vegf-wet-amd-and-dme-candidate-at-the-association-for-research-in-vision-and-ophthalmology-arvo-2022-ann/

Ashvattha Therapeutics Presents Phase 1 Safety Data in ... Data showed single subcutaneous doses of D-4517.2 were safe and well tolerated in healthy subjects; D-4517.2 exposure in healthy subjects ...

7. modernretina.com modernretina.com/view/phase-1-safety-data-for-subcutaneous-anti-vegf-candidate-for-wet-amd-dme-presented-at-arvo

Phase 1 safety data for subcutaneous anti-VEGF candidate ... The data presented at ARVO showed single subcutaneous doses of D-4517.2 were safe, well-tolerated in healthy subjects.