Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

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 registered on ANZCTR


Registration number
ACTRN12622001507774
Ethics application status
Approved
Date submitted
6/10/2022
Date registered
2/12/2022
Date last updated
2/12/2022
Date data sharing statement initially provided
2/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase I, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Oral Doses of ACT004 in Healthy Adult Subjects
Scientific title
A Phase I, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Oral Doses of ACT004 in Healthy Adult Subjects
Secondary ID [1] 307902 0
NA
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Kidney fibrosis 327535 0
Condition category
Condition code
Renal and Urogenital 324638 324638 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomized, double-blind, placebo-controlled dose-escalation study to evaluate the safety, tolerability and Pharmacokinetics (PK) of ACT004 after administration of single (Part A) and multiple (Part B) oral doses in healthy adult subjects. Approximately five sequential dose cohorts (single oral doses of 100, 200, 400, 600 and 800 mg ACT004) will be evaluated as single ascending doses (SAD) in Part A. Select appropriate dose cohort(s) (seven consecutive days for respectively daily oral) based on the Part A and safety review committee (SRC), which will be evaluated as multiple ascending doses (MAD) in Part B. For each dose cohort in this study, ten healthy subjects will be randomized in an 8:2 ratio to receive either ACT004 or a placebo in SAD and MAD. Based on the safety, tolerability, and PK data of the previous dose cohort, the SRC will make decisions on whether to proceed with dose escalations, dosage adjustments, use of sentinel subjects or termination of the study, etc. Higher dose cohort(s) may be attempted additionally if judged necessary by the SRC. Each subject will receive only one dosing regimen in this study. The proposed doses/dosing frequency of ACT004 may be adjusted over the course of the whole study, and cohorts may be added or removed depending on the exposure of ACT004 in humans.

* Part A - SAD study (Cohort A1-A5) Approximately 35 days: Healthy subjects will be screened within 28 days prior to dosing. Subjects will be admitted to the clinical site on Day -1 and dosed orally on Day 1 under fasting conditions (fasting for at least 10 hours) with approximately 240 mL of warm water . Following completion of all safety assessments and sampling for Pharmacokinetic analysis, subjects will be monitored at clinical site and discharged on Day 4 and return for an end of study (EOS) visit on Day 7. EOS visit will also be the early termination (ET) visit if required (to be completed within 3 days of ET wherever possible). ACT004 capsule will be administered to subjects orally at a starting dose of 100 mg and increased to 200, 400, 600 and 800 mg in sequential dosing cohorts. Dose escalation will be based on the SRC review of blinded safety data including Adverse Event (AE) data, clinical laboratory results, ECGs, vital signs and physical examinations findings, and PK data up to and including Day 7. Once a minimum of 10 subjects randomized in a given cohort complete the Day 7 study visit, all safety and PK data will be reviewed by the SRC prior to dose escalation to the next dose cohort. For the safety of subjects, two sentinel subjects will be randomly dosed (ACT004: placebo = 1:1) at least 24 hours prior to the remaining subjects in each cohort. Once safety is confirmed, the remaining 8 subjects will be dosed at 7:1 to receive ACT004 or a placebo.

*Part B - MAD study (Cohort B1) Approximately 45 days : MAD cohorts may commence at the discretion of the SRC, after the safety data from a SAD cohort at a higher dose (and hence higher exposure) have been evaluated. Dosing will commence with the lowest dose cohort (B1). subjects will receive either ACT004 capsule or placebo once daily with approximately 240 mL of warm water for 7 consecutive days from Day 1 to Day 7. Subjects should receive ACT004 or placebo once daily at the same time whenever possible. Subjects will be required to take the study drug on an empty stomach (fasting for at least 10 h) in the morning of Day 1 and Day 7, and have breakfast 2 hour after dosing, lunch and dinner 4 and 10 hours after dose. The planned dose regimen for Part B (MAD study) may be adjusted by the SRC according to safety, tolerability, and PK results of Part A. Healthy subjects will be screened within 28 days prior to dosing and admitted to the clinical site on Day -1. Eligible subjects will be randomized into appropriate dose cohort(s) in an 8:2 ratio to receive ACT004 or placebo on Day 1 to Day 7. Following completion of all PK sample collection and safety assessments, subjects will be discharged on Day 10 and followed up on Day 14. Dose escalation will be based on SRC review of blinded safety data including AE data, clinical laboratory results, ECGs, vital signs and physical examinations findings up to and including Day 14 along with PK data up to and including Day 10. Once a minimum of 10 subjects randomized in a given cohort complete the Day 14 study visit, all safety and PK data will be reviewed by the SRC prior to dose escalation to the next dose cohort.

Telemetry monitoring will be performed continuously from pre-dose to 6 hour post dose in both Part A and Part B. Telemetry monitoring includes blood pressure, heart rate, and respiratory rate. During telemetry monitoring items as vital signs or 12 Lead- ECG can be monitored once.

Adherence to the intervention will be done via Drug Accountability.
Intervention code [1] 324480 0
Treatment: Drugs
Comparator / control treatment
Placebo will be supplied as gelatin capsules in bottles and labeled in accordance with International Committee on Harmonization of Good Clinical Practice (ICH GCP) and any other local regulatory requirements. Placebos are composed of 102mg of lactose hydrate, 1 mg of sucorse octaacetate and 1mg of polyethylene glycol 6000.

* Part A - SAD study: For the safety of subjects, two sentinel subjects will be randomly dosed (ACT004: placebo = 1:1) at least 24 hours prior to the remaining subjects in each cohort. Once safety is confirmed, the remaining 8 subjects will be dosed in 7:1 to receive ACT004 or placebo..

* Part B - MAD study: MAD cohorts may commence at the discretion of the SRC, after the safety data from a SAD cohort at a higher dose have been evaluated. Healthy subjects will be screened within 28 days prior to dosing and admitted to the clinical site on Day -1. Eligible subjects will be randomized into appropriate dose cohort(s) in an 8:2 ratio to receive ACT004 or placebo on Day 1 to Day 7. Following completion of all PK sample collection and safety assessments, subjects will be discharged on Day 10 and followed up on Day 14.
Control group
Placebo

Outcomes
Primary outcome [1] 332611 0
To evaluate the safety and tolerability of ACT004 following single and multiple oral dose administration in healthy adult subjects. The parameters assessed for the safety endpoints include:
- incidence and severity of AEs - AEs and SAEs will be assessed for severity and causality (relationship of the event to the investigational product) by the study investigator using the specified grading definitions Common Terminology Criteria for Adverse Events (CTCAE) (V5.0) as 5 grades.
- incidence of abnormalities of laboratory tests (hematology, blood biochemistry, coagulation and urinalysis) .Subjects should be fasting for at least 8 hours (no food consumption, but water is allowed) prior to blood draws for blood biochemistry assessments.
- ECGs - One 12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals.
- vital signs - including blood pressure, pulse, respiratory rate and body temperature. It is recommended that vital signs measurement method follows routine clinical practice at the study site and the methodology should be consistent for each subject for the duration of the study. The observed values will be recorded and assessed as 'normal', 'abnormal not clinically significant' or 'abnormal clinically significant'
- physical examinations - A complete physical examination will be required at screening, and an abbreviated physical examination will be acceptable for all the other visits. A complete physical examination will include, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. An abbreviated physical examination will include, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen).
Timepoint [1] 332611 0
Assessed during single ascending doses at the following time points:
- Adverse events (AEs) - AEs assessment will be performed throughout the study period. The severity of AEs will be graded as per common terminology criteria for adverse events (CTCAE) (V5.0) as 5 grades: Grade 1, Grade 2, Grade 3, Grade 4, and Grade 5. AEs will be collected from the time written informed consent is signed until the time when the subject has completed or withdrawn from the clinical study.
- Laboratory tests- Laboratory tests including hematology, blood biochemistry, coagulation and urinalysis are performed at Screening, Day -1, Day 2 post dose, Day 4 post dose, and at End of the Study Visit (EOS) on Day 7. Subjects should be fasting for at least 8 hours (no food consumption, but water is allowed) prior to blood draws for blood biochemistry assessments.
- ECGs- ECGs are performed at Screening, 1 hour prior to study drug administration, 0.5 hour, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after study drug administration, on Day 4 (discharge day) and End of Study/ End of Termination Visit on Day 7.
- Physical Examination- Physical examination (including height and weight; a complete physical examination will be required at screening, and an abbreviated physical examination will be acceptable for all the other visits). A physical examination will be performed at Screening pre dose, Day -1 pre dose, Day 4 (discharge day) post-dose and EOS/ET visit on Day 7 post dose.
- Vital Signs - Vital signs include measurements of blood pressure, pulse, respiratory rate, and body temperature. Vital Signs are performed at screening, 1 hour prior to and 0.5 hour, 1 hour, 2 hours, 4 hours, 6 hours,8 hours, 24 hours, 48 hours after study drug administration, on discharge day on Day 4, and on End of study visit/ End of Termination visit on Day 7. Measurements will be taken in duplicate at screening and on Day -1, an average of which will be used for inclusion/ exclusion criteria check. At all other time points as single measurements.

Assessed during Multiple ascending doses at the following time points:
- Adverse events (AEs) - AEs assessment will be performed throughout the study period. The severity of AEs will be graded as per common terminology criteria for adverse events (CTCAE) (V5.0) as 5 grades: Grade 1, Grade 2, Grade 3, Grade 4, and Grade 5. AEs will be collected from the time written informed consent is signed until the time when the subject has completed or withdrawn from the clinical study.
- Laboratory tests- 'Laboratory tests including hematology, blood biochemistry, coagulation, and urinalysis. Laboratory tests can be performed either before or after study drug administration and the time point will be determined by the PI. Tests completed at Screening, Day -1 (admission - except for when the previous results are within 7 days), Day 2/Day 4/Day 6, Day 8, Day 10 (discharge), and at End of Study Visit (EOS) on Day 14.
- ECGs- ECGs are performed at Screening, Day -1 (admission), 1 hour prior to study drug administration, 0.5 hour, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours after study drug administration on Day 1, 1 hour prior to study drug administration on Day 2/Day 4/Day 6, Day 8 and Day 10 (discharge) and End of Study/End of Termination Visit on Day 14.
- Vital Signs - Vital signs include measurements of blood pressure, pulse, respiratory rate and body temperature. Vital signs are performed at screening, 1 hour prior to and 0.5 hour 1 hour, 2 hours, 4 hours, 6 hours, 8 hours after study drug administration on Day 1, 1 h prior to study drug administration from Day 2 to Day 9, on discharge at Day 10 and on EOS/ET visit on Day 14. Measurements will be taken in duplicate at screening and on Day -1, an average of which will be used for inclusion/ exclusion criteria check. At all other time points as single measurements.
- Physical Examination- 'Physical Examination is performed at Screening, Day -1 (admission), Day 2/Day 4/Day 6, Day 8, Day 10 (discharge) and EOS/ET visit on Day 14. Physical examinations can be performed either before or after study drug administration and the time point will be determined by the PI. The timepoint of physical examination has to be consistent throughout the study. Significant findings presented prior to the first dose of the study drug will be recorded as Medical History and significant findings made after the first dose of the study product that meets the definition of TEAE will be recorded as an Adverse Event/ Serious Adverse Event (AE/SAE).
Secondary outcome [1] 414048 0
To evaluate the PK characteristics of ACT004 after administration of single and multiple oral doses in healthy adult subjects.
Pharmacokinetic parameters of ACT004 including but not limited to, maximum concentration (Cmax), time to reach maximum concentration (Tmax), area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf), area under the plasma concentration-time curve from time 0 to the time t of last quantifiable concentration (AUC0-t), apparent volume of distribution (Vd/F), elimination half-life (t1/2), clearance (CL/F), mean residence time (MRTinf), and elimination rate constant (Lambda-z) will be evaluated.

Blood and Urine Samples are used for assessing the above PK characteristics.
Timepoint [1] 414048 0
PK is assessed during single ascending doses at the following timepoints:
Day 1 at Predose (-1 to 0 hour), 0.25 hour, 0.5 hour, 1 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 12 hour post dose and 24 hour post dose.

PK is assessed during Multiple ascending doses at the following timepoints:
Day 1 at Predose (-1 to 0 hour), 0.25 hour, 0.5 hour, 1 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 12 hour post dose, Day 2 Predose (-1 to 0 hour). Day 5 Predose (-1 to 0 hour) , Day 6 Predose (-1 to 0 hour) and on Day 7 Predose (-1 to 0 hour), 0.25 hour, 0.5 hour, 1 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 12 hour post dose and Day 8 at 24 hours. The PK sampling time point on Day 2 corresponds to the point 24 hours after dosing on Day 1. The PK sampling time point on Day 8 corresponds to the point 24 hours after dosing on Day 7. The PK sampling times might need to be adjusted for subsequent cohorts in order to better characterize PK profile of ACT004. The PK sampling time point on Day 7 corresponds to the point 24 hours after dosing on Day 6. The PK sampling times might need to be adjusted for subsequent cohorts in order to better characterize PK profile of ACT004.

Pharmacokinetic Assessments Urine sample are assessed at following timepoints:
- Part A - Day 1 Predose (-1 to 0 hour), 0-4 hour post dose, 4-8 hour post dose, 8-12 hour post dose, 12-24 hour post dose.
- Part B- Day 1 Predose (-1 to 0 hour), 0-4 hour post dose, 4-8 hour post dose, 8-12 hour post dose, 12-24 hour post dose.
- Part B- Day 7 Predose (-1 to 0 hour), 0-4 hour post dose , 4-8 hour post dose, 8-12 hour post dose, 12-24 hour post dose.

Eligibility
Key inclusion criteria
1. Healthy male and female subjects, 18-55 years of age (both inclusive) at the time of screening.
2. Subjects able to provide a signed and dated informed consent and/or assent document indicating that the subject has been informed of all pertinent aspects of the study before any assessment is performed.
3. Subjects who agree to comply with protocol restrictions, including refraining from consuming alcohol, caffeinated beverages (e.g., tea, coffee, etc.), and tobacco or nicotine containing products from 24 hours before Day 1 until the last PK blood sample collection is finished; able to remain in house for the confinement period of the study without interruption.
4. Body mass index (BMI, weight [kg]/height2 [m2]) within 18.0-28.0 kg/m2 (both inclusive).
5. A female participant is eligible to participate if she is not pregnant and intending to become pregnant or breastfeeding, and at least one of the following conditions applies:
- surgically sterile (by means of hysterectomy and/or bilateral oophorectomy) or post-menopausal for at least one year, defined as amenorrhea for 12 consecutive months without another cause and with a follicle stimulating hormone (FSH) level greater than or equal to 40 mIU/mL at screening.
- a woman of childbearing potential and using a contraceptive method that is highly effective, with a failure rate of less than 1%, during the treatment period and for at least 1 month after the last dose of study treatment.
6. Male subjects must be willing to remain abstinent (when this is in line with their preferred and usual lifestyle), or, if engaging in sexual intercourse with a female partner of childbearing potential, willing to use a condom in addition to having the female partner use a highly effective method of female contraception from the time of the first study drug administration until 30 days following the last dose of study drug. This requirement does not apply to subjects in a same-sex relationship, subjects with female partners of non-childbearing potentials, or vasectomized subjects who have not undergone any reversal procedure. Male subjects must also be willing to not donate sperms from the time of the first study drug administration until 30 days after the last dose of study drug.
7. No clinically significant abnormal values on vital signs, B-ultrasound and 12-lead ECG. QT interval corrected for heart rate according to Fridericia's formula (QTcF) must be within the following ranges: QTcF less than or equal to 450 msec for male subjects, and QTcF less than or equal to 470 msec for female subject. Assessment may be repeated once if deemed appropriate by the Investigator.
8. No clinically significant abnormal findings noted during screening for medical history and physical examination, or clinically significant abnormal results during screening clinical laboratory tests, including white blood cells (WBCs), liver function and kidney function. Assessment may be repeated once if deemed appropriate by the Investigator.
9. Negative urine drug screen and alcohol breath testing at screening and on Day -1.
10. Ability to swallow all study drugs.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Subjects who have a clinically relevant intolerance or allergy to drugs, or are known or suspected to have hypersensitivity to any ingredient in the study drugs;
2. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs;
3. History or clinical manifestations of any clinically significant gastrointestinal, renal, urologic, bronchopulmonary, neurological, psychiatric, cardiovascular, endocrinological, hematological or allergic disease, metabolic disorder or cancer, at the discretion of the Investigator;
4. Current or chronic history of liver disease or known hepatic or biliary abnormalities, including ALT, aspartate aminotransferase (AST), alkaline phosphatase and bilirubin greater than upper limit of normal (ULN);
5. Current or history of clinically significant cardiac arrhythmias (symptomatic or asymptomatic);
6. Subjects who have had any significant acute infection, e.g., influenza, local infection, acute gastrointestinal symptoms or any other clinically significant illness within two weeks of dose administration. Subjects with a mild upper respiratory infection may be enrolled at the discretion of the Investigator;
7. Creatinine clearance less than 90 mL/min (using the Cockcroft-Gault method based on serum creatine and actual body weight) at screening;
8. Major illness or surgery (except for minor outpatient surgery) within past 3 months of study Day 1, or planned surgery during the study period;
9. Intolerance to direct venepuncture;
10. Participation in any clinical study with an investigational drug, biologic or device within 4 weeks or 5 times the half-life of the specific product if applicable (whichever is longer) since the last dosing or the last use of the investigation drug, biologic or device, prior to the first dosing of ACT004;
11. Donated blood greater than 400 mL or significant blood loss equivalent to 400 mL, or received blood transfusion within 1 months of screening, or have plans to donate blood during the study;
12. History of malignancy within 5 years of screening visit (excluding non-melanoma skin cancer that has been resected);
13. Positive test at screening of any of the following: serum hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV RNA or HCV Ab) or human immunodeficiency virus 1 and 2 (HIV Ab);
14. Recent administration or plans to receive administration of any live vaccine within 12 weeks before Day 1;
15. Use of any other drug, including prescription and over-the-counter medications, within one week of first dosing or within 5 times the elimination half-life of the medication (whichever is longer) prior to first dosing. Exceptions may be made on a case-by-case basis following discussion and agreement between the Investigator and the sponsor.
- Paracetamol at a dose of less than 2 g in 24 hours but no more than 1 g in 4 hours is permitted;
- Dietary vitamins may be allowed at the discretion of the Investigator (e.g., vitamin D taken at a standard replacement dose and at a time remote from IP administration);
- Herbal supplements are not permitted;
16. Unwilling to refrain from caffeinated beverages (i.e., tea, coffee, etc.) from 24 hours before Day -1 until completion of the confinement period;
17. Use of food or beverages likely to influence liver metabolism or inhibit CYP2C9, within 14 days prior to the first dose of the study drug (e.g., star fruit, pomelos, grapefruit & Seville oranges);
18. History of significant alcohol abuse within 6 months of screening or any indication of regular use of more than 14 units of alcohol per week for female subjects and 21 units of alcohol per week for male subjects (1 Unit = 360 mL of beer or 45 mL of alcohol 40% or 150 mL of wine) and, unwilling to refrain from consumption of alcohol from 24 hours before Day -1 until completion of the confinement period;
19. Use of tobacco or nicotine products or smoking within 30 days (more than 5 cigarettes per day) prior to screening, and, unwilling to refrain from 24 hours before Day -1 until completion of the confinement period;
20. Known or suspected history of drug abuse (e.g., amphetamines [AMP], Methamphetamines [MET], methadone [MTD], barbiturates [BAR], benzodiazepines [BZO], cocaine [COC], opiates [OPI], methyl enedioxy, methamphetamine [MDMA], phencyclidine [PCP], tetrahydrocannabinol [THC]) within the past 2 years or presence of drug abuse within 3 months before screening, or evidence of such abuse on laboratory assays at screening unless explained by a therapeutic dose of a prescribed medication that was ceased at least 14 days prior to Day 1. Drug screening may be repeated once at the discretion of the Investigator;
21. Pregnant (positive pregnancy test) or lactating women;
22. Any factor, which in the opinion of the Investigator would jeopardize the evaluation or safety or be associated with poor adherence to the protocol, rendering the subject unsuitable for participating 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)
This is a randomized, double-blind, placebo-controlled study with limited access to the randomization code. ACT004 and placebo capsules will be identical in physical appearance. The treatment each participant will receive will not be disclosed to the Investigator, study centre personnel, subject, Sponsor and their representatives. Emergency unblinding should only be performed when necessary, in order to treat the participant in an emergency. During the treatment period unblinding can be performed via IWRS by the Investigator in case of medical emergency when it is essential for effective treatment of the participant.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The treatment codes will be held according to the interactive web response system (IWRS).

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
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Pharmacokinetic analysis:
Plasma concentration-time profiles will be obtained by plotting mean concentrations against blood sampling time points. Plasma concentrations at each blood sampling time point are subject to descriptive statistical analysis.
Descriptive statistical analyses will be performed for PK parameters by groups.

Safety analysis:
AEs will be coded using the preferred terms (PT) from Medical Dictionary for Regulatory Activities (MedDRA) of the most recent version at the time of database lock and grouped by system organ class (SOC). The severity of AEs will be graded. The number of events, number and percentage of subjects will be summarized for all treatment-emergent adverse events (TEAEs, defined as any AE occurring from the start of dosing to the end of the study), SAEs, study drug-related TEAEs, study drug-related SAEs, and TEAEs leading to study discontinuation by SOC, PT, and group. In addition, the severity of TEAEs, SAEs and their relationship to study drug will also be summarized by SOC, PT, and cohort.
Descriptive statistical analyses will be performed for the baseline values, post-dose values, and changes from baseline for vital signs, physical examinations, laboratory tests, and 12-lead ECG.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2023
Actual
Date of last participant enrolment
Anticipated
1/11/2023
Actual
Date of last data collection
Anticipated
15/02/2024
Actual
Sample size
Target
82
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 23217 0
Nucleus Network - Geelong
Recruitment hospital [2] 23219 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 38585 0
3004 - Melbourne
Recruitment postcode(s) [2] 38586 0
3220 - Geelong

Funding & Sponsors
Funding source category [1] 312175 0
Commercial sector/Industry
Name [1] 312175 0
Accendatech AU Pty Ltd.
Country [1] 312175 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Accendatech AU Pty Ltd.
Address
Accendatech AU Pty Ltd.
Suite 2903, 201 Elizabeth St. Sydney NSW 2000
Country
Australia
Secondary sponsor category [1] 313845 0
Commercial sector/Industry
Name [1] 313845 0
Avance Clinical Pty Ltd
Address [1] 313845 0
Avance Clinical Pty Ltd
Level 1, Ann Nelson Drive
Thebarton, SA 5031, Australia
Country [1] 313845 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311560 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 311560 0
55 commercial Road, Melbourne, VIC 3004
Ethics committee country [1] 311560 0
Australia
Date submitted for ethics approval [1] 311560 0
31/08/2022
Approval date [1] 311560 0
31/10/2022
Ethics approval number [1] 311560 0

Summary
Brief summary
This is a randomized, double-blind, placebo-controlled dose-escalation study to evaluate the safety, tolerability and PK of ACT004 after administration of single (Part A) and multiple (Part B) oral doses in healthy adult subjects. Approximately five sequential dose cohorts (single oral doses of 100, 200, 400, 600 and 800 mg ACT004) will be evaluated as single ascending doses (SAD) in Part A. Select appropriate dose cohort(s) (seven consecutive days for respectively daily oral) based on the Part A and safety review committee (SRC), which will be evaluated as multiple ascending doses (MAD) in Part B. For each dose cohort in this study, ten healthy subjects will be randomized in an 8:2 ratio to receive either ACT004 or placebo in SAD and MAD. Based on the safety, tolerability, and PK data of the previous dose cohort, the SRC will make decisions on whether to proceed with dose escalations, dosage adjustments, use of sentinel subjects or termination of the study, etc. Higher dose cohort(s) may be attempted additionally if judged necessary by the SRC. Safety data up to Day 7 in SAD study and up to Day 14 in MAD study will be reviewed prior to dose escalation by the SRC. Dosing will be escalated in a sequential fashion if approved by the SRC. Dose escalations will be terminated when there are 1/2 or more subjects with grade 2 adverse events (AEs), or 1/3 or more subjects with grade 3 AEs, or 1 or more subjects with serious adverse events (SAEs) related to the study drug in the current dose cohort.
Each subject will receive only one dosing regimen in this study. The proposed doses/dosing frequency of ACT004 may be adjusted over the course of the whole study, and cohorts may be added or removed depending on the exposure of ACT004 in humans.
For the safety of subjects, two sentinel subjects will be randomly dosed (ACT004: placebo=1:1) at least 24 hours prior to the remaining subjects in each cohort. Once safety is confirmed, the remaining 8 subjects will be dosed in 7:1 to receive ACT004 or placebo.
Trial website
Trial related presentations / publications
Public notes
This is the first clinical study of ACT004 to evaluate the safety, tolerability and PK profile in a population. The selection of healthy adult volunteers for this human study meets ethical requirements. At the same time, the sample homogeneity of healthy people is high, which can reduce the influence of individual differences on safety and PK characteristics results; on the other hand, selecting healthy people can avoid the impact of disease burden and concomitant medications on the safety evaluation of experimental drugs, and healthy people can help researchers observe more reliable toxicity data. This study is also randomized and double-blinded with regard to treatment with ACT004 and matching placebo in order to prevent bias in treatment allocation and in the assessment of effect. The Investigator, as well as the Sponsor and their representatives involved in the monitoring or conducting the study, and the subjects will all be blinded to the study drug codes.

Step 7 -Recruitment- (This will be deleted)- Date of last data collection - the longest one for data collection is the 3 months of pregnancy. Therefore, this has been updated as 15-Feb-2024

Contacts
Principal investigator
Name 121542 0
Dr Sam Francis
Address 121542 0
Nucleus Network Melbourne
Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, VIC
Country 121542 0
Australia
Phone 121542 0
+61 7 3707 2720
Fax 121542 0
Email 121542 0
s.francis@nucleusnetwork.com.au
Contact person for public queries
Name 121543 0
Ms Nucleus Network Melbourne
Address 121543 0
Nucleus Network Melbourne
Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, VIC
Country 121543 0
Australia
Phone 121543 0
+61 1800 243 733
Fax 121543 0
Email 121543 0
melbourne@nucleusnetwork.com
Contact person for scientific queries
Name 121544 0
Dr Sam Francis
Address 121544 0
Dr Sam Francis
Nucleus Network Melbourne
Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, VIC
Country 121544 0
Australia
Phone 121544 0
+61 385939800
Fax 121544 0
Email 121544 0
s.francis@nucleusnetwork.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Privacy and Intellectual property rights considerations


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.