Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05506540




Registration number
NCT05506540
Ethics application status
Date submitted
9/08/2022
Date registered
18/08/2022
Date last updated
25/08/2022

Titles & IDs
Public title
A First-in-human Single Ascending Dose/Multiple Ascending Dose Study of ENN0403 in Healthy Subjects
Scientific title
A Phase 1, First-in-human, 2-part, Randomized, Double-blind, Placebo-controlled, Parallel-group, Single Ascending Dose and Multiple Ascending Dose (SAD/MAD) Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ENN0403 in Healthy Adult Subjects
Secondary ID [1] 0 0
ENN0403-P1-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ENN0403 1mg
Treatment: Drugs - ENN0403 4mg
Treatment: Drugs - ENN0403 10mg
Treatment: Drugs - ENN0403 20mg
Treatment: Drugs - ENN0403 30mg
Treatment: Drugs - ENN0403 20mg (Fed)
Treatment: Drugs - ENN0403 6mg QD X 14 Days
Treatment: Drugs - ENN0403 12mg QD X 14 Days
Treatment: Drugs - ENN0403 20mg QD X 14 Days
Treatment: Drugs - Placebo

Experimental: Single Ascending Dose, ENN0403 1 mg - Single oral use of ENN0403 at dose level 1 mg, in fasted state.

Experimental: Single Ascending Dose, ENN0403 4 mg - Single oral use of ENN0403 at dose level 4 mg, in fasted state.

Experimental: Single Ascending Dose, ENN0403 10 mg - Single oral use of ENN0403 at dose level 10 mg, in fasted state.

Experimental: Single Ascending Dose, ENN0403 20 mg - Single oral use of ENN0403 at dose level 20 mg, in fasted state.

Experimental: Single Ascending Dose, ENN0403 30 mg - Single oral use of ENN0403 at dose level 30 mg, in fasted state.

Experimental: Single Ascending Dose, ENN0403 20 mg (Fed) - Single oral use of ENN0403 at dose level 30 mg, after high calorie and high-fat breakfast meal.

Experimental: Multiple Ascending Dose, ENN0403 6 mg - ENN0403 capsules for oral administration, 6 mg QD X 14 Days

Experimental: Multiple Ascending Dose, ENN0403 12 mg - ENN0403 capsules for oral administration, 12 mg QD X 14 Days

Experimental: Multiple Ascending Dose, ENN0403 20 mg - ENN0403 capsules for oral administration, 20 mg QD X 14 Days

Placebo Comparator: Single/Multiple Ascending Dose, placebo capsules for oral adminstration - Placebo capsules for oral administration


Treatment: Drugs: ENN0403 1mg
ENN0403 capsules for oral use

Treatment: Drugs: ENN0403 4mg
ENN0403 capsules for oral use

Treatment: Drugs: ENN0403 10mg
ENN0403 capsules for oral use

Treatment: Drugs: ENN0403 20mg
ENN0403 capsules for oral use

Treatment: Drugs: ENN0403 30mg
ENN0403 capsules for oral use

Treatment: Drugs: ENN0403 20mg (Fed)
ENN0403 capsules for oral use

Treatment: Drugs: ENN0403 6mg QD X 14 Days
ENN0403 capsules for oral use

Treatment: Drugs: ENN0403 12mg QD X 14 Days
ENN0403 capsules for oral use

Treatment: Drugs: ENN0403 20mg QD X 14 Days
ENN0403 capsules for oral use

Treatment: Drugs: Placebo
Placebo capsules for oral use
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with treatment emergent adverse events (TEAE) following ENN0403 administration
Timepoint [1] 0 0
From first dose of ENN0403 administration till 7 days after last dose of ENN0403 administration.
Secondary outcome [1] 0 0
Maximum Plasma Concentration [Cmax]
Timepoint [1] 0 0
Single Ascending Dose (SAD) part: up to Day 4, 72 hours post dose; Multiple Ascending Dose (MAD) part: up to Day 17, 72 hours post last dose
Secondary outcome [2] 0 0
Area Under the Curve [AUC]
Timepoint [2] 0 0
Single Ascending Dose (SAD) part: up to Day 4, 72 hours post dose; Multiple Ascending Dose (MAD) part: up to Day 17, 72 hours post last dose

Eligibility
Key inclusion criteria
- Capable of giving signed informed consent.

- 18 to 55 years old (inclusive).

- 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.

- Computerized (12-lead) ECG recording without signs of clinically relevant pathology or
showing no clinically relevant deviations as judged by the PI.

- Test negative for COVID-19.

- Test negative for HBsAg, anti-HBc, anti-hepatitis C virus (HCV) antibodies, anti-human
immuno deficiencyvirus (HIV) 1 and 2 antibodies, and tuberculosis.

- Have a negative urine drug screen and a negative alcohol breath test.

- Nonsmoker or occasional smoker and willingness to refrain from smoking during study.

- Ability and willingness to abstain from alcohol during study.

- not pregnant, not breastfeeding; apply contraception methods for child-bearing
potential subjects.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- 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.

- 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.

- 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.

- 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.

- In the 12-lead ECG assessment, QTcF >450 ms for male subjects or >470 ms for female
subjects.7. Estimated glomerular fltration rate <90 mL /min (using the Cockcroft-Gault
formula) at Screening.

- ALT or aspartate aminotransferase>1.5ULN.

- 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
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
17/02/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/05/2022
Sample size
Target
Accrual to date
Final
69
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 0 0
- Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
EnnovaBio Australia Pharmaceuticals Pty Ltd
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05506540
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/ct2/show/NCT05506540