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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05105607




Registration number
NCT05105607
Ethics application status
Date submitted
26/10/2021
Date registered
3/11/2021
Date last updated
21/09/2022

Titles & IDs
Public title
A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of D-4517.2 After Subcutaneous Administration in Healthy Participants
Scientific title
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
Secondary ID [1] 0 0
D-4517-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neovascular Age-related Macular Degeneration 0 0
Diabetic Macular Edema 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - D-4517.2

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.

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.

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.

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.


Treatment: Drugs: D-4517.2
Subcutaneous (SC) injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Adverse Events
Timepoint [1] 0 0
Day 1 up to Day 15
Secondary outcome [1] 0 0
Maximum Plasma Concentration (Cmax) of D-4517.2
Timepoint [1] 0 0
Day 1 up to Day 3
Secondary outcome [2] 0 0
Time to Maximum Plasma Concentration (tmax) of D-4517.2
Timepoint [2] 0 0
Day 1 up to Day 3
Secondary outcome [3] 0 0
Apparent Terminal Rate Constant (kel) of D-4517.2
Timepoint [3] 0 0
Day 1 up to Day 3
Secondary outcome [4] 0 0
Apparent Elimination Half-life (t1/2) of D-4517.2
Timepoint [4] 0 0
Day 1 up to Day 3
Secondary outcome [5] 0 0
Area Under the Concentration-time Curve Based On the Last Measurable Concentration (AUC0-t)
Timepoint [5] 0 0
Day 1 up to Day 3
Secondary outcome [6] 0 0
Area Under the Concentration-time Curve from Time Zero to Infinity (AUC0-inf)
Timepoint [6] 0 0
Day 1 up to Day 3
Secondary outcome [7] 0 0
Clearance (CL) of D-4517.2
Timepoint [7] 0 0
Day 1 up to Day 3

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/01/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/08/2022
Sample size
Target
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Nucleus Network (Brisbane) - Brisbane
Recruitment postcode(s) [1] 0 0
4006 - Brisbane

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Ashvattha Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT05105607
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05105607