None listed
Conditions
Brief summary
This is a FIH, randomized, double-blind, placebo-controlled, dose-escalation study to investigate the safety, tolerability, PK, and PD of ENN0403 after single and multiple oral dose administration in healthy adult subjects. The study will include 2 parts which will proceed in a parallel staggered manner: Part A, a single ascending dose (SAD) study and Part B, a multiple ascending dose (MAD) study. Approximately 80 healthy adult subjects will be enrolled at a single site in Australia, in up to 6 cohorts in Part A (SAD study), including a Food Effect (FE) study, and up to 4 cohorts in Part B (MAD study). Part A is for the single dose use of IP, while Part B is once daily use for 14 consecutive days. Each cohort will include 8 subjects (6 receiving ENN0403 and 2 receiving placebo). Each subject will be enrolled in only 1 cohort and receive only one dose regimen in this study. Dosing will be escalated in a sequential fashion, contingent on a review of safety, tolerability, and available PK data of the previous dose level by a Safety Review Committee (SRC). The proposed dose levels/dosing frequency of ENN0403 may be adjusted over the course of the whole study and cohorts may be added or removed depending on the emerging safety, tolerability, and available PK data.
Interventions
Treatment Drug: ENN0403 oral capsules
1. Part A, Single Ascending Dose (SAD) Arms: Part A evaluates single-dose administration of ENN0403 at dose levels 1, 4, 10, 20 and 30 mg respectively in cohort A1-A5. The dose level of 20 mg has also been evaluated in a preliminary Food Effect (FE) study in cohort A6. While cohrot A1-A5 will receive a single dose of investigational drug under fasted state (after an overnight fast of at least 10 hours prior to dosing), cohort A6 will receive a high calorie (
Treatment Drug: ENN0403 oral capsules 1. Part A, Single Ascending Dose (SAD) Arms: Part A evaluates single-dose administration of ENN0403 at dose levels 1, 4, 10, 20 and 30 mg respectively in cohort A1-A5. The dose level of 20 mg has also been evaluated in a preliminary Food Effect (FE) study in cohort A6. While cohrot A1-A5 will receive a single dose of investigational drug under fasted state (after an overnight fast of at least 10 hours prior to dosing), cohort A6 will receive a high calorie (approximately 800 to 1000 calories) and high-fat (approximately 50% of total caloric content of the meal) breakfast meal following an overnight fast of at least 10 hours; the investigational drug will be administered 30 minutes after the start of the meal. 2. Part B, Multiple Ascending Dose (MAD) Arms: Part B evaluates multiple dose administration of ENN0403 at 6, 12, and 20 mg once daily (QD) for 14 consecutive days, respectively in cohort B1-B3. Each cohort included 8 subjects (6 receiving ENN0403 and 2 receiving placebo). Each subject will be enrolled in only 1 cohort and receive only one dose regimen in this study. Dosing will be escalated in a sequential fashion, contingent on a review of safety, tolerability, and available PK data of the previous dose level by a Safety Review Committee (SRC). The MAD study will commence only after SRC review of the data from Cohort A3 in Part A (SAD study) and cumulative data from previous completed cohorts. Further dose level decisions for Part B will be guided by the emerging safety, tolerability, PK, and PD data from Part A as well as completed cohorts of Part B. All dose administrations will be performed at the study site under the supervision of appropriately trained staff. A hand and mouth check will be performed following each dose administration to make sure the dose has been swallowed. The details of investigational drug administration will be recorded in both the source documents and eCRF(electronic Case Report Form).
Sponsors
EnnovaBio Australia Pharmaceuticals Pty Ltd
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Capable of giving signed informed consent 2. 18 to 55 years old (inclusive) 3. BMI of 18 to 30 kg/m2 (inclusive); body weight >50 to <100 kg for male subjects or >45 to <100 kg for female subjects 4. Computerized (12-lead) ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the PI 5. Test negative for COVID-19 6. Test negative for HBsAg, anti-HBc, anti-hepatitis C virus (HCV) antibodies, anti-human immunodeficiency virus (HIV) 1 and 2 antibodies, and tuberculosis. 9. Have a negative urine drug screen and a negative alcohol breath test. 10. Nonsmoker or occasional smoker and willingness to refrain from smoking during study. 11. Ability and willingness to abstain from alcohol during study. 13. not pregnant, not breastfeeding; apply contraception methods for child-bearing potential subjects.
Exclusion criteria
1. History of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease in the opinion of the Investigator within 12 months prior to Screening. 2. Any disease or take any medication that affects IP absorption, distribution, metabolism, and excretion. 3. Family history of sudden death or of congenital prolongation of the QTc interval or known congenital prolongation of the QTc interval or any clinical condition known to prolong the QTc interval. 4. Presence of malignancy including hematological malignancies. Subjects with a history of basal cell or squamous cell carcinoma that has been treated with no evidence of recurrence within 3 years of Screening will be allowed for inclusion, as judged by the Investigator. 5. Any current active infections, including localized infections, or any recent history (within 1 week prior to IP administration) of active infections, cough or fever; or a history of recurrent or chronic infections. 6. In the 12-lead ECG assessment, QTcF >450 ms for male subjects or >470 ms for female subjects. 7. Estimated glomerular filtration rate <90 mL/min (using the Cockcroft-Gault formula) at Screening. 8. ALT or aspartate aminotransferase >1.5 × ULN. 9. Have received any live vaccines (bacterial or viral) within 12 weeks prior to Screening or intend to receive a live vaccine during the study period or within 30 days after the last dose of the IP.
Outcome results
None listed