Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000744459
Ethics application status
Approved
Date submitted
11/06/2025
Date registered
15/07/2025
Date last updated
15/07/2025
Date data sharing statement initially provided
15/07/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
A clinical study to compare the safety and tolerability of two formulations of a new Systemic Sclerosis drug in Healthy Participants - Part B
Scientific title
A 2-Part, Single-Dose, Multiple Period Crossover Relative Bioavailability Study of Asengeprast Ethanolamine (MEA) Salt Formulation vs Asengeprast Free Acid Formulation in Adult Healthy Volunteers - Part B
Secondary ID [1] 314615 0
CER-Asengeprast-BA-01
Universal Trial Number (UTN)
Trial acronym
SAFARi
Linked study record
This study is a follow-up study with a new Investigational Medicinal Product (IMP) formulation to compare the bioavailability against the IMP investigated in NCT04647890
This study is also part B to ACTRN12625000733471 (part A).

Health condition
Health condition(s) or problem(s) studied:
Systemic sclerosis Scleroderma 337783 0
Condition category
Condition code
Inflammatory and Immune System 334125 334125 0 0
Connective tissue diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is Part B, a randomised sequence, single-dose, three -sequence, five-period, crossover study to assess the relative bioavailability of asengeprast MEA salt formulation vs asengeprast free acid formulation in adult healthy volunteers.

Approximately thirty-three (33) participants will be enrolled in a 3 sequence, 3 treatment period crossover with a single dose of asengeprast 400 mg free acid in a fasted state, and a single dose of MEA salt in both a fed and fasted state. It is anticipated that the selected MEA salt dose will be no more than 500 mg with the exact dose determined in part A of this study (ACTRN12625000733471).

- This study consists of a 28-day screening period before proceeding to 3 treatment periods with follow-up visits.
- In each of the treatment periods, participants will be confined to the clinic and will be discharged following completion of the last study procedure on Day 3. Participants will return to the clinic for an outpatient follow-up visit 7 days after the last dose of study drug.

Participants will be randomised to receive a single oral dose of asengeprast (as free acid in a fasted state, and MEA salt in a fed and fasted state) within a 3 sequence, 3 period crossover study with at least a 7-day washout period between periods..

The treatment arms included in each sequence are;
• 400 mg asengeprast free acid formulation (reference formulation), in a fasted state
• Asengeprast MEA salt (test formulation), in a fasted state.
• Asengeprast MEA salt (test formulation), in a fed state (after high fat high calorie meal).
The Asengeprast MEA salt dose will be the same for fed and fasted treatment arms and will be determined in part A of this study (ACTRN12625000733471). Fasted state requires participants to fast overnight for at least 10 hours prior to dosing and until 4 hours after dosing. According to FDA guidance, a high fat meal consists of 800-1000 calories in which approximately 50% of calories from fat. An example of a high fat breakfast is two eggs fried in butter, two strips of bacon, two slices of toast with butter, four ounces (115 grams) of hash brown potatoes, eight ounces (240 mLs) of whole milk. Fasted and fed state and dose administration adherence will be monitored by the trial site during the confinement period at the Phase I unit.

Pharmacokinetic (PK) blood samples for the analysis of asengeprast concentrations will be collected prior to dosing (0 hour) on Day 1 and up to 192 hours post-dose in each period. Therefore, plasma PK samples will be collected at 1 hour prior to pre-dose, then at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and Day 8: 144 - 192 hours post Day 1 dose in order to characterise the absorption phase.

Adverse events (AEs) and concomitant medications will be assessed and recorded from the time of consent to the completion of the study follow-up visit. Safety and tolerability will be assessed by monitoring and recording of adverse events (AEs) and serious AEs (SAE), clinical laboratory test results, vital sign measurements, 12-lead electrocardiogram (ECG) results, and physical examination findings.

Individual doses in the form of oral capsules will be provided for participants by phase I-unit staff on the day of administration in a suitable container. All participants will receive asengeprast formulations at the study site under the supervision of appropriate study personnel.
Intervention code [1] 331251 0
Treatment: Drugs
Comparator / control treatment
400 mg asengeprast free acid formulation
Control group
Active

Outcomes
Primary outcome [1] 341779 0
To evaluate the relative bioavailability of the oral dose(s) of asengeprast MEA salt vs asengeprast free acid 400 mg fasted dosing in healthy adult male and female participants.
Timepoint [1] 341779 0
At each treatment period PK will be taken on Day 1 at 1 hour prior to pre-dose, then at 1, 2, 3, 4, 6, 8, 12, 24 hours (Day 2), 36 hours (Day 2), 48-hours (Day 3) post-dose and Day 8 (follow-up visit/End of study (EoS) visit): 144 - 192 hours post Day 1 dose.
Secondary outcome [1] 448646 0
To characterise the single-dose pharmacokinetics (PK) of the selected highest oral dose of asengeprast MEA salt vs asengeprast free acid 400 mg in healthy adult male and female participants
Timepoint [1] 448646 0
At each treatment period PK will be taken on Day 1 at 1 hour prior to pre-dose, then at 1, 2, 3, 4, 6, 8, 12, 24 hours (Day 2), 36 hours (Day 2), 48-hours (Day 3) post-dose and Day 8 (follow-up visit/End of study (EoS) visit): 144 - 192 hours post Day 1 dose.
Secondary outcome [2] 448649 0
To assess dose proportionality of asengeprast MEA salt
Timepoint [2] 448649 0
At each treatment period PK will be taken on Day 1 at 1 hour prior to pre-dose, then at 1, 2, 3, 4, 6, 8, 12, 24 hours (Day 2), 36 hours (Day 2), 48-hours (Day 3) post-dose and Day 8 (follow-up visit/End of study (EoS) visit): 144 - 192 hours post Day 1 dose.
Secondary outcome [3] 448650 0
To evaluate the safety and tolerability of oral dosing of asengeprast free acid 400 mg and asengeprast MEA salt formulation in healthy adult male and female participants
Timepoint [3] 448650 0
• Treatment emergent adverse events from first dose of study drug to End of Study (EoS) - Day 1, Day 2, Day 3, Day 4, Day5, Day 6, Day 7 and Day 8/EoS • Physical examination from first dose of study drug - Day -1, Day 1, Day 3, and Day 8/EoS. • Vital signs (respiratory rate, temperature, blood pressure, heart rate and pulse oximetry) from first dose of study drug - Day1, Day 2, Day 3, and Day 8/EoS. On dosing days - Day 1 vitals to be taken within 1 hour prior to dosing, then 30 minutes, 1 hour ± 5 mins, 2 hours ± 5 mins, 4 hours ± 5 mins and 8 hours ± 15 mins post dose. • 12-lead electrocardiograms (ECG) from first dose of study drug - Day 1, Day 3, and Day 8/EoS. On dosing days - Day 1 ECGs are to be performed within 1 hour prior to IMP administration (pre-dose) and then at 2 hours, 4 hours and 8 hours post dose. • Safety laboratory results (haematology, biochemistry, coagulation, and urinalysis) from first dose of study drug - Day -1, Day 2, and Day 8/EoS. • Use of concomitant medications from D-1, Day1, Day 2, Day 3, Day 4, Day5, Day 6, Day 7 and Day 8/EoS.

Eligibility
Key inclusion criteria
Participants must meet all the following criteria:
1. Must be capable of giving signed informed consent
2. Male or female participants between greater than or equal to 18 and less than or equal to 65 years of age (inclusive) at the screening visit.
3. In good general health without clinically significant medical history as determined by the investigator.
4. Body weight greater than or equal to 50 kg for males and greater than or equal to 47 kg for females and body mass index (BMI) within the range of 18.0 – 32.0 kg/m2 (inclusive)
5. Contraceptive Methods
a. Female subjects of child-bearing potential must agree to use highly effective contraceptive methods from the screening period to 90 days after the last dose of the study drug. In addition, they must abstain from egg collection or donation during the same period. The male partner of a female subject also needs to agree to use condoms during this period.
b. Male subjects considered fertile must agree to not plan to father a child, not donate sperm, and take effective contraceptive methods from the screening period to 90 days after the last dose of the study drug. The female partner of male subjects also needs to agree to use a highly effective method of female contraception during this period
6. Ability to follow study instructions and likely to complete all visits as assessed by the investigator.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants are excluded from the study if any of the following criteria apply:
1. Any participant that has been enrolled and given IMP into Part A of the study are excluded from participating in Part B.
2. Have received any Investigational medicinal product (IMP) within 30 days or 5 half-lives prior to Screening, whichever is longer.
3. Have received a live attenuated vaccine within 60 days or a registered vaccine within 30 days prior to the first dose of the IMP or plans to receive such vaccines during the study.
4. Have used any prescription medications within the 14 days (or 5 half-lives, whichever is longer) prior to Day 1, and/or non-prescription drugs and herbal remedies (such as St. John's Wort [Hypericum perforatum]), within the 7 days prior to Day 1, or anticipate needing to take medications during the study period. Over-the-counter multivitamins will be permitted. If needed, paracetamol (less than or equal to 2 grams/day) may be used. Any questions regarding concomitant medications should be directed to the Sponsor.
5. Have a known allergy or sensitivity or contraindication to the IMP or its excipients.
6. Have any clinically significant abnormality at Screening determined by medical history, vital signs, physical examination, blood chemistry, haematology, urinalysis or a 12-lead electrocardiogram (ECG), including but not limited to:
a. Repeated measurement of systolic blood pressure 140 mmHg, diastolic blood pressure < 40 or >90 mmHg (inclusive), or pulse rate 100 bpm, pulse oximetry 1.5 × upper limit of normal (ULN). A single repeat of ALT is allowed within a single screening period to determine eligibility.
c. Bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin 30 mg/g at screening. Note: eGFR calculated using CKD-EPI equation.
7. Have received blood products within 1 month prior to Screening.
8. Have a history of thyroidectomy or thyroid disease that required medication within the past 12 months.
9. Have had serious angioedema episodes within the previous 3 years or requiring angioedema medication in the previous two years.
10. Have a bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with blood draws in the opinion of the investigator, contraindicate blood draws.
11. Altered absorption and/or excretion of orally administered drugs e.g. Crohn’s disease, Gilbert’s syndrome, stomach or intestinal surgery etc.
12. Have a history of or current clinically significant gastrointestinal, hepatic, renal, cardiovascular, respiratory, endocrine, oncological, immunodeficiency, neurological, metabolic, haematological or autoimmune disorder; or a history of or current tuberculosis, epilepsy, diabetes or glaucoma as determined by the investigator.
13. Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, and TB testing: a positive (not indeterminate) QuantiFERON-TB Gold test. NOTE: The QuantiFERON-TB Gold test is dependent on previous treatment(s). This test may not be suitable if previous treatment(s) produced significant immunosuppression.
14. Major surgery within 3 months prior to Day 1 or planned during the study period.
15. Presence of hepatitis B surface antigen or positive hepatitis C antibody or RNA test result at Screening. NOTE: participants with positive hepatitis C antibody due to prior resolved disease can be enrolled if a confirmatory negative hepatitis C RNA test result is obtained. NOTE: The RNA test is optional and participants with negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing.
16. Positive human immunodeficiency virus (HIV) antibody test.
17. Have a positive alcohol breath test or urine screen for drugs of abuse at Screening or Day -1, or evidence of drug or alcohol abuse in the investigator’s opinion.
18. History of drug/chemical or alcohol abuse within 6 months prior to Day -1. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol/spirits) or positive alcohol breath test at screening and Day -1.
19. Use of tobacco or nicotine-containing products in excess of the equivalent of 5 cigarettes per day.
20. Consumption of red wine, grapefruit, or grapefruit -related citrus fruits (e.g., Seville oranges, pomelos, fruit juices) within 7 days prior to the first dose of asengeprast.
21. Are unable to provide a blood sample without undue trauma or distress.
22. Have a history of or current clinically relevant social, clinical, or psychiatric condition which, in the opinion of the investigator, makes the participant unsuitable for participation in the study.
23. Are pregnant, breastfeeding, or plan to become pregnant during the study period.
24. Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
25. Have any other medical condition or significant co-morbidities, or any finding during Screening or Day -1, in the opinion of the investigator, may interfere with the study objectives or put the participants at risk.

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
An independent biostatistician will create a computer-generated randomisation schedule using a permutated block randomisation technique. A manual randomisation process will be followed at site where the next available randomisation number on the randomisation schedule will be assigned to the next eligible participant to determine the assigned treatment sequence, and the randomisation number will be captured in the clinical database.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Bio-availability
Statistical methods / analysis
A unique screening identification (ID) number will be allocated to each participant who provides informed consent.

On Day -1 / Day 1 of Treatment Period 1, participants will be assigned a randomisation number. The number encodes the participant’s treatment sequences, according to the randomisation schedule generated prior to the study by the Statistics Department. Each participant will be dispensed study intervention, labelled with his/her unique randomisation number, throughout the study.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
16/09/2025
Actual
Date of last participant enrolment
Anticipated
20/10/2025
Actual
Date of last data collection
Anticipated
13/11/2025
Actual
Sample size
Target
33
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 28037 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 44241 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 319175 0
Commercial sector/Industry
Name [1] 319175 0
Certa Therapeutics Pty Ltd
Country [1] 319175 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Certa Therapeutics Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 321641 0
None
Name [1] 321641 0
Address [1] 321641 0
Country [1] 321641 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317759 0
Bellberry Human Research Ethics Committee A
Ethics committee address [1] 317759 0
Ethics committee country [1] 317759 0
Australia
Date submitted for ethics approval [1] 317759 0
07/05/2025
Approval date [1] 317759 0
03/06/2025
Ethics approval number [1] 317759 0

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

Contacts
Principal investigator
Name 142042 0
Dr Philip Ryan
Address 142042 0
Nucleus Network Pty Ltd., Level 3, 549 St Kilda Road, Melbourne Victoria 3004
Country 142042 0
Australia
Phone 142042 0
+61385939801
Fax 142042 0
Email 142042 0
[email protected]
Contact person for public queries
Name 142043 0
Darren Kelly
Address 142043 0
Certa Therapeutics Level 9, 31 Queen St, Melbourne, Victoria 3000
Country 142043 0
Australia
Phone 142043 0
+61396570700
Fax 142043 0
Email 142043 0
[email protected]
Contact person for scientific queries
Name 142044 0
Darren Kelly
Address 142044 0
Certa Therapeutics Level 9, 31 Queen St, Melbourne, Victoria 3000
Country 142044 0
Australia
Phone 142044 0
+61396570700
Fax 142044 0
Email 142044 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.