A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of D-4517.2 After Subcutaneous Administration in Healthy Participants

A Phase 1 Open-Label Single-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of D-4517.2 (Hydroxyl Dendrimer VEGFR Tyrosine Kinase Inhibitor) After Subcutaneous Administration in Healthy Volunteers

The primary objective of this study is to evaluate the safety and tolerability of D-4517.2 after single subcutaneous (SC) doses in healthy participants.

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema; Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Drug: D-4517.2

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia, 4006
      • Nucleus Network (Brisbane)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Is a healthy man or woman age 18 to 65 years, inclusive, at the Screening Visit;
2. Has the ability to understand and sign the written informed consent form (ICF) and local medical privacy authorization forms, which must be obtained prior to any study related procedures being completed;
3. Body mass index (BMI) between 18 and 32 kg/m^2, inclusive, with body weight ≤ 100 kg;
4. Is in general good health, based upon the results of a medical history assessment, physical examination, vital signs, and laboratory profile, as judged by the Investigator;
5. Female participants of non-childbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before the Screening Visit) or postmenopausal, defined as spontaneous amenorrhea for at least 1 years, with follicle-stimulating hormone (FSH) in the postmenopausal range at screening, based on the central laboratory's ranges;
6. Female participants of childbearing potential (i.e., ovulating, premenopausal, and not surgically sterile) and all male participants must use a medically accepted contraceptive regimen (including hormonal contraceptives) during their participation in the study and for 30 days after the last administration of study drug. Medically accepted contraceptive methods are defined as those with 90% or greater efficacy;

7. Acceptable methods of contraception for male participants enrolled in the study include the following:

   • Condoms or surgical sterilization of participant at least 26 weeks before the Screening Visit (vasectomy);

   Acceptable methods of contraception for female participants enrolled in the study include the following:

   • Surgical sterilization of participant at least 26 weeks before the Screening Visit (includes hysterectomy or bilateral tubal ligation, oophorectomy, or salpingectomy);
   • Intrauterine device for at least 4 weeks before the Screening Visit; or
   • Hormonal contraception (oral, implant, injection, ring, or patch) for at least 4 weeks before the Screening Visit;
8. If male, participants must agree to abstain from sperm donation through 90 days after administration of the last dose of study drug;
9. Female participants may not be pregnant, lactating, or breastfeeding;
10. Female participants of childbearing potential must have negative result for pregnancy test at screening and Check-in;
11. Participants must have a negative test result for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVab), and human immunodeficiency virus (HIV) antibody at screening;
12. Participants must have an estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73m^2 at screening;
13. Participants must have a negative urine test for drugs of abuse, cotinine, and breath alcohol test at screening and Check-in; and
14. Participants must be willing and able to abide by all study requirements and restrictions.

Exclusion Criteria:

1. Evidence of clinically significant hematologic, renal, endocrine, pulmonary, cardiac, gastrointestinal (GI), hepatic, psychiatric, neurologic, immunologic, allergic disease (including multiple or clinically significant drug allergies), or any other condition that, in the opinion of the Investigator, might significantly interfere with the absorption, distribution, metabolism, or excretion of study drug, or place the participant at an unacceptable risk as a participant in this study;
2. Evidence of systemic inflammation as measured by C-reactive protein above the upper limit of normal as measured by local lab;
3. History of malignancy (other than successfully treated basal cell or squamous cell skin cancer);
4. History or presence of an abnormal ECG that, in the opinion of the Investigator, is clinically significant;
5. Laboratory results (serum chemistry, hematology, coagulation, and urinalysis) outside the normal range at screening and Check-in and considered clinically significant in the opinion of the Investigator. Any elevation of aspartate transaminase (AST) and alanine transaminase (ALT) above the upper limit of normal at screening and/or Check-in is exclusionary. One retest of an exclusionary laboratory result is allowed at the discretion of the Investigator;
6. Has had an acute illness considered clinically significant by the Investigator within 30 days prior to screening;
7. History of alcoholism or drug abuse within 2 years prior to screening;
8. Has used any product containing nicotine within 90 days prior to screening or intends to use any product containing nicotine during the course of the study;
9. Has had any immunizations (live vaccines) in the 4 weeks prior to screening; COVID-19 vaccination within 7 days of Day 1;
10. Has used medications that affect GI motility or gastric emptying; such as metoclopramide, proton pump inhibitors, and H2 blockers; within 30 days prior to Day 1;
11. Has used any prescription or over-the-counter medication (with exception of acetaminophen), vitamins/herbal supplements (with the exception of hormonal contraceptives) within 14 days prior to Day 1;
12. Has used any other study drug within 30 days or 5 half-lives of the drug (whichever is longer) prior to Day 1;
13. Has lost or donated >450 mL of whole blood or blood products within 30 days prior to screening;
14. Investigator has reason to believe that the participant may be unable to fulfill the protocol visit schedule or requirements;
15. Has any finding that, in the view of the Investigator or Medical Monitor, would compromise the participant's safety requirements; or
16. Is employed by the Sponsor, the Contract Research Organization (CRO), or the study site (permanent, temporary contract worker, or designee responsible for the conduct of the study), or is a family member (spouse, parent, sibling, or child) of the Sponsor, CRO, or study site employee.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: 0.25 mg/kg D-4517.2; Participants will be administered a single dose of 0.25 mg/kg D-4517.2. A sentinel participant will be enrolled for each cohort. After the sentinel participant completes Day 3, the safety review committee (SRC) will determine if it is safe to continue with the enrollment of the remaining 3 participants in the cohort. The SRC will also determine the dose escalation to the next cohort.	Drug: D-4517.2; Subcutaneous (SC) injection
Experimental: Cohort 2: 0.5 mg/kg D-4517.2; Participants will be administered a single dose of 0.5 mg/kg D-4517.2. A sentinel participant will be enrolled for each cohort. After the sentinel participant completes Day 3, the SRC will determine if it is safe to continue with the enrollment of the remaining 3 participants in the cohort. The SRC will also determine the dose escalation to the next cohort.	Drug: D-4517.2; Subcutaneous (SC) injection
Experimental: Cohort 3: 1.0 mg/kg D-4517.2; Participants will be administered a single dose of 1.0 mg/kg D-4517.2. A sentinel participant will be enrolled for each cohort. After the sentinel participant completes Day 3, the SRC will determine if it is safe to continue with the enrollment of the remaining 3 participants in the cohort. The SRC will also determine the dose escalation to the next cohort.	Drug: D-4517.2; Subcutaneous (SC) injection
Experimental: Cohort 4: 2.0 mg/kg D-4517.2; Participants will be administered a single dose of 2.0 mg/kg D-4517.2. A sentinel participant will be enrolled for each cohort. After the sentinel participant completes Day 3, the SRC will determine if it is safe to continue with the enrollment of the remaining 3 participants in the cohort.	Drug: D-4517.2; Subcutaneous (SC) injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events	Day 1 up to Day 15

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Plasma Concentration (Cmax) of D-4517.2	Day 1 up to Day 3
Time to Maximum Plasma Concentration (tmax) of D-4517.2	Day 1 up to Day 3
Apparent Terminal Rate Constant (kel) of D-4517.2	Day 1 up to Day 3
Apparent Elimination Half-life (t1/2) of D-4517.2	Day 1 up to Day 3
Area Under the Concentration-time Curve Based On the Last Measurable Concentration (AUC0-t)	Day 1 up to Day 3
Area Under the Concentration-time Curve from Time Zero to Infinity (AUC0-inf)	Day 1 up to Day 3
Clearance (CL) of D-4517.2	Day 1 up to Day 3

Collaborators and Investigators

• Sponsor: Ashvattha Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2022
• Primary Completion (Actual): August 31, 2022
• Study Completion (Actual): August 31, 2022

Study Registration Dates

• First Submitted: October 26, 2021
• First Submitted That Met QC Criteria: October 26, 2021
• First Posted (Actual): November 3, 2021

Study Record Updates

• Last Update Posted (Actual): September 21, 2022
• Last Update Submitted That Met QC Criteria: September 19, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Diabetic Macular Edema; Neovascular Age-related Macular Degeneration; D-4517.2
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Wet Macular Degeneration
• Other Study ID Numbers: D-4517-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes