Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000234617
Ethics application status
Approved
Date submitted
30/01/2023
Date registered
6/03/2023
Date last updated
1/06/2024
Date data sharing statement initially provided
6/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Part 1 and Part 3: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics of AC-101
Scientific title
A Single Center, Randomized, Double-blind, Placebo-controlled, Sequential Parallel Group, Single and Multiple Ascending Dose Study Following Oral Administration in Healthy Subjects to Evaluate the Safety, Tolerability, Pharmacokinetics of AC-101
Secondary ID [1] 308676 0
AC-101-AU-PhIa
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Inflammatory Bowel Disease 328602 0
Condition category
Condition code
Oral and Gastrointestinal 325614 325614 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Accro Bioscience is developing AC-101, a potent and selective oral small molecule inhibitor of RIPK2, indicated for treatment of inflammatory bowel disease (IBD).
Investigational Product (IP): AC-101
Dosage Form: Tablet
Mode of Administration: Oral
Part 1 Single Ascending Dose: A total of 40 participants in 5 dose levels including 50, 100, 200, 400 and 600 mg will be evaluated;
All doses will be administered after an overnight fast of at least 10 hours for all Cohorts of Part 1
8 Participants 6 (study drug): 2 (placebo) in each cohort.
Cohort 1: 50mg AC-101 single oral administration on Day 1
Cohort 2: 100mg AC-101 single oral administration on Day 1
Cohort 3: 200mg AC-101 single oral administration on Day 1
Cohort 4: 400mg AC-101 single oral administration on Day 1
Cohort 5: 600mg AC-101 single oral administration on Day 1
Part 3 Multiple Ascending Dose: A total of 30 participants in 3 dose levels including 50, 100, 200 mg will be evaluated;
All doses will be administered after an overnight fast of at least 10 hours for all cohorts of Part 3
10 Participants 8 (study drug): 2 (placebo) in Cohort 1, Cohort 2 and Cohort 3
Cohort 1: 50mg AC-101 once daily for a consecutive 7 days i.e., Day 1 to Day 7
Cohort 2: 100mg AC-101 once daily for a consecutive 7 days i.e., Day 1 to Day 7
Cohort 3: 200mg AC-101 once daily for a consecutive 7 days i.e., Day 1 to Day 7
All doses of study drug will be administered orally with approximately 240mL of room temperature water. Water consumption will be restricted from 1 h prior to dosing until 2 h after dosing, when water will be given to maintain adequate hydration. For some participants, they may require extra water. Providing additional water eg. 100mL to be allowed and documented to assist with dose administration if required.
In part 1 and part 3 the participants are dosed at the site, they will receive study treatment directly from the Investigator or designee, under medical supervision. Immediately after dose administration, visual inspection of the mouth and hands will be performed for each subject. The date and time of each dose administered will be recorded in the source documents. The dose of study treatment and study participant identification will be confirmed at the time of dosing by a member of the study site staff other than the person administering the study treatment.
Intervention code [1] 325147 0
Treatment: Drugs
Comparator / control treatment
The placebo tablets will be identical in appearance to the AC-101 and will be administered orally.
Placebo to match consists of microcrystalline cellulose, lactose hydrate, croscarmellose sodium, magnesium stearate and Opadry® II 85F620077.
Control group
Placebo

Outcomes
Primary outcome [1] 333454 0
To evaluate the safety and tolerability of AC-101 following oral dose administration assessed by,
- Incidence and severity of adverse events (AE) will be coded using the Medical Dictionary for Regulatory Activities (MedDRA version 25.1)
- Clinically significant changes from baseline in laboratory evaluations (hematology, blood biochemistry, urine routine and coagulation function tests)
- 12-lead Electrocardiograms (12-lead ECGs)
- Vital signs (systolic/diastolic Blood Pressure using sphygmomanometer, pulse rate, respiratory rate is measured manually by the medical staff using clock, oral temperature is measured using tympanic thermometer and oxygen saturation)
- Physical examinations includes weight is measured weighing scales, general observations, skin examination, lymph nodes examination, head and neck examination, examinations for cardiac, respiratory, abdominal and neurological system
Timepoint [1] 333454 0
Adverse Events:
Part 1 SAD - Daily from Screening to Day 8
Part 3 MAD - Daily from Screening to Day 16

Clinical Laboratory tests (hematology, blood biochemistry, urine routine and coagulation function tests):
Part 1 SAD - Screening, on Day -1, Day 2, Day 3, hematology, liver, kidney function panel and coagulation will be tested on Day 5., Day 8 hematology and Chemistry
Part 3 MAD - Screening, on Day -1, Day 3, Day 6, Day 9, hematology, liver, kidney function panel will be tested on Day 16.

12-lead ECGs:
Part 1 SAD - Screening, on Day -1, Day 1 pre-dose and at 30 min, 1h, 2h, 24h, 48h post-dose.
Part 3 MAD - Screening, on Day -1, and on Day 1 pre-dose and at 30 min, 1h, 2h post-dose; and at 30 min post-dose on Day 2, 3, 4, 5, 6; and Day 7, pre-dose and at 30 min, 1h, 2h, 24h, 48h post-dose

Vital Signs:
Part 1 SAD - Screening, on Day -1, Day 1 pre-dose and at 30 min, 1h, 2h, 24h, 48h post-dose, Day 5 and Day 8
Part 3 MAD - Screening, on Day -1, and on Day 1 pre-dose and at 30 min, 1h, 2h post-dose; and at 30 min post-dose on Day 2, 3, 4, 5, 6; and on Day 7 pre-dose and at 30 min, 1h, 2h, 24h and 48h post-dose, Day 16
Physical Examination:
Part 1 SAD - Screening, on Day -1, Day 2, Day 3, Day 5 and Day 8 post-dose.
Part 3 MAD - Screening, on Day -1, Day 3, Day 6, Day 9, Day 16 post-dose.
Secondary outcome [1] 417160 0
To characterize the pharmacokinetics (PK), and determine the effects of food on PK of AC-101 following oral single and multiple ascending dose administration by collecting blood samples. The parameters for PK assessment are:
- Maximum observed plasma concentration (Cmax)
- Time of maximum observed plasma concentration (Tmax)
- Terminal Phase Elimination Half Life (t1/2)
- Area under the plasma concentration curve from time 0 to last (AUC0-last)
- Area under the plasma concentration curve from time 0 to infinity (AUCinf)
- Area under the plasma concentration curve from time to 0 to t (AUC0-t)
- Mean residence time (MRT)
- Apparent clearance (CL/F)
- Apparent volume of distribution (Vz/F)
- Apparent Terminal Rate Constant (kel)
- Minimum drug concentration at steady-state (Cmin,ss)
- Maximum plasma concentration at steady state (Cmax,ss)
- Average plasma drug concentration during a dosing interval at steady-state (Cav,ss)
- steady-state fluctuation coefficient (DF)
- accumulation ratio (rac)
Timepoint [1] 417160 0
Blood samples for PK assessment are collected at the following timepoints:
Part 1 SAD:
Day 1 - Predose and at 15min, 30 min, 45 min, 1h, 1.5h, 2h, 4h, 8h, 12h post-dose
Day 2 i.e., 24h post-dose
Day 3 i.e., 48h post-dose

Part 3 MAD
Day 1 and Day 7 - Predose and at 15min, 30 min, 45 min, 1h, 1.5h, 2h, 4h, 8h, 12h post-dose
Day 2 and Day 8 - 24h post-dose
Pre-dose (within 1h prior to dosing) on Day 3, Day 4, Day 5, and Day 6
Day 9 - 48h post-dose

Eligibility
Key inclusion criteria
1. Are capable of giving informed consent and complying with study procedures.
2. The age between 18 and 60 years, inclusive.
3. Body mass index (BMI) of 18.0 to 32.0 kg/m2 inclusive and body weight not less than 50 kg for male and 45 kg for female.
4. Female subjects have a negative serum pregnancy test result at screening and Day -1, and meet one of the following criteria:
• Using highly effective method of contraception such as implants, injectables, combined oral contraceptives, intrauterine devices (IUDs), intrauterine hormone-releasing system (IUS) at least 1 month prior to screening and willing to continue the control for the duration of the study, and until 3 months after dosing with the study drug.
• Surgically sterile for at least 3 months prior to screening by one of the following means:
- Bilateral salpingectomy (with or without oophorectomy)
- Surgical hysterectomy
- Vasectomized partner
- Bilateral oophorectomy (with or without hysterectomy)
• Postmenopausal, defined as the following:
- Last menstrual period greater than 12 months prior to screening
- Postmenopausal status confirmed by serum follicle stimulating hormone (FSH) level of greater than or equal to 40 IU/L at screening.
5. Male subjects with female partners of child bearing potential must agree to use condoms and use highly effective method of contraception with female partner for the duration of the study and until 3 months after dosing with the study drug and must refrain from donating sperm for this same period.
6. Subjects who are exclusively in same-sex relationships (contraception is not required for female participants who are in same-sex) and subjects who abstain completely for the duration of the study and for 3 months after the last study treatment are acceptable;
7. Considered healthy by the Investigator, based on subject’s reported medical history, full physical examination, clinical laboratory tests, 12-lead ECG, and vital signs;
8. Willing and able to adhere to study restrictions and to be confined at the clinical research center.
Minimum age
18 Years
Maximum age
60 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 food intolerances; mild and inactive hay fever is permitted), 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 subject at an unacceptable risk as a participant in this study;
2. Has had an acute illness considered clinically significant by the Investigator within 30 days prior to screening, minor colds are permitted;
3. 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. One retest of an exclusionary laboratory result is allowed at the discretion of the Investigator.
4. Taken any drug that inhibits or induces liver drug-metabolizing enzymes 30 days prior to screening; Excessive consumption of special diets (including dragon fruit, mango, grapefruit, grapefruit juice, pomelo, star fruit, Seville oranges, Seville orange marmalade or other products containing grapefruit, pomelo, star fruit or Seville oranges etc.) and/or xanthine-rich diets (including chocolate, tea, coffee, cola, etc.) or other effects that affect the absorption, distribution, metabolism, excretion and other factors of the drug 7 days prior to study drug administration;
5. Clinically significant history with sequelae of gastrointestinal tract, liver, kidney, or other diseases known to interfere drug absorption, distribution, metabolism or excretion.
6. Prolongation of QTcF (greater than 450 msec for males and greater than 470 msec for females) at screening.
7. Known current or history of malignancy.
8. Positive blood screen for hepatitis C antibody, hepatitis B surface antigen or human immunodeficiency virus (HIV) antibody.
9. A hospital admission or major surgery within 90 days prior to screening.
10. A history of prescription drug abuse, or illicit drug use within 3 months prior to screening.
11. A history of alcohol abuse according to medical history within 3 months prior to screening.
12. Has more than 5 cigarettes/week within 30 days prior to screening or intends to use any product containing nicotine during the course of the study;
13. A positive screen for alcohol, cotinine, and/or drugs of abuse at screening or Day -1.
14. An unwillingness or inability to comply with food and beverage restrictions during study participation (ie lactose intolerance; vegans and vegetarians are permitted in Part 1 and 3), and refrain from ingestion of dragon fruit, mango, grapefruit, grapefruit juice, pomelo, star fruit, Seville oranges, Seville orange marmalade or other products containing grapefruit, pomelo, star fruit or Seville oranges from 7 days prior to study drug administration to the end of the study;
15. Has had any immunizations (live vaccines) in the 4 weeks prior to screening.
16. Has used medications that affect GI motility or gastric emptying within 30 days prior to Day 1.
17. Has used any prescription or over-the-counter medication (with exception of acetaminophen at less than 2 g/day until 48 hours prior to dosing), vitamins/herbal supplements (with the exception of hormonal contraceptives) within 14 days or 5 half-lives of the drug (whichever is longer) prior to Day 1.
18. Poor venous access.
19. Has lost or donated greater than 450 mL of whole blood or blood products within 30 days prior to screening.
20. Taken any investigational drug within 30 days, or 5 half-lives whichever is longer.
21. Female who are pregnant, or breastfeeding, Positive pregnancy test result.
22. Any condition or finding that in the Investigators’ opinion would put the subject or study conduct at risk if the subject were to participate in the study.

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
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
3/04/2023
Actual
12/04/2023
Date of last participant enrolment
Anticipated
10/07/2023
Actual
28/08/2023
Date of last data collection
Anticipated
2/11/2024
Actual
Sample size
Target
70
Accrual to date
Final
70
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 23767 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 39212 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 312910 0
Commercial sector/Industry
Name [1] 312910 0
Accro Bioscience (Australia) Pty Ltd
Country [1] 312910 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Accro Bioscience (Australia) Pty Ltd
Address
Level 7, 330 Collins Street, Melbourne Victoria 3000
Country
Australia
Secondary sponsor category [1] 314588 0
None
Name [1] 314588 0
Address [1] 314588 0
Country [1] 314588 0
Other collaborator category [1] 282515 0
Commercial sector/Industry
Name [1] 282515 0
Novotech (Australia) Pty Limited
Address [1] 282515 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 282515 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312184 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 312184 0
Ethics committee country [1] 312184 0
Australia
Date submitted for ethics approval [1] 312184 0
23/01/2023
Approval date [1] 312184 0
02/03/2023
Ethics approval number [1] 312184 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 123770 0
Dr Ofer Gonen
Address 123770 0
Nucleus Network Melbourne
Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, Victoria,
Australia
Country 123770 0
Australia
Phone 123770 0
+61 0385939800
Fax 123770 0
Email 123770 0
[email protected]
Contact person for public queries
Name 123771 0
Ofer Gonen
Address 123771 0
Nucleus Network Melbourne
Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, Victoria,
Australia
Country 123771 0
Australia
Phone 123771 0
+61 0385939800
Fax 123771 0
Email 123771 0
[email protected]
Contact person for scientific queries
Name 123772 0
Xiaohu Zhang
Address 123772 0
Accro Bioscience (Australia) Pty Ltd
Level 7, 330 Collins Street, Melbourne, Victoria, Australia 3000
Country 123772 0
Australia
Phone 123772 0
+61451332620
Fax 123772 0
Email 123772 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.