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Trial registered on ANZCTR


Registration number
ACTRN12625000694415
Ethics application status
Approved
Date submitted
13/02/2025
Date registered
1/07/2025
Date last updated
1/07/2025
Date data sharing statement initially provided
1/07/2025
Type of registration
Retrospectively registered

Titles & IDs
Public title
First-time-in-human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RB201 in Healthy Adult Subjects
Scientific title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Two-Part (Single-Ascending Dose and Multiple-Ascending Dose), First-time-in-human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RB201 in Healthy Adult Subjects
Secondary ID [1] 313856 0
RB201-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
autoimmunity 336515 0
Condition category
Condition code
Inflammatory and Immune System 333024 333024 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: RB201 - small molecule inhibitor of MALT1
Dosage Formulation: Capsule
Route: Oral

Experimental:
Part 1: Single ascending dose (SAD) in up to six dose cohorts (10 mg, 25 mg, 75, 150, 250, and 375 mg by mouth once daily), including one cohort to evaluate the effect of high-fat food on the PK profile (the 150 mg cohort). Total of eight subjects per dose cohort (including the food effect cohort): the first two subjects will be sentinel subjects, randomized 1:1 to receive RB201 or placebo. The next six subjects will be randomized 5:1 to receive RB201 or placebo. Subjects will be housed at the Phase 1 unit and dosing administered and verified (to ensure adherence) by the staff.

Part 1 (food effect): The food effect cohort will have one dose administered in a fasted state as in all the other SAD cohorts. Then after a suitable washout period as determined by half-life PK data from prior cohorts, another dose will be administered but this time following a high-fat high-calorie breakfast to eat prior to the second dose. This meal will
contain standard high-fat breakfast foods such as eggs, bacon, toast with butter, hash browns and a cup of full cream milk. The participants are instructed to "finish as much of the meal as you can within 30 minutes prior to dosing." They will then undergo safety assessments and PK testing.

Part 2: Multiple ascending doses (MAD) for 7 days in two dose cohorts (provisionally 75 mg and 150 mg). These doses will be determined by the sponsor after discussion with the SMC based on safety and PK data from the SAD cohorts. Within each cohort, eight subjects are randomized two to receive placebo and six to receive RB201. The MAD cohorts will be initiated once the equivalent SAD cohort has been completed through Day 7 and the SMC has approved dose-escalation to the next or later SAD cohort(s), such that the anticipated steady state PK exposure in the MAD cohort is estimated to be less than or equal to the PK exposures that demonstrated safety in the SAD portion of the study. Subjects will be housed at the Phase 1 unit and dosing administered and verified (to ensure adherence) by the staff.
Intervention code [1] 330473 0
Treatment: Drugs
Comparator / control treatment
Healthy adult volunteers will receive placebo (capsules containing microcrystalline cellulose 102)
Control group
Placebo

Outcomes
Primary outcome [1] 340686 0
To assess the safety of single and multiple doses of RB201 when administered by the oral route at escalating doses in healthy volunteers
Timepoint [1] 340686 0
SAD: Baseline, Day 1 (treatment day) through day 14. MAD: Baseline. Day 1 to Day 7 (treatment days) through day 21
Primary outcome [2] 340926 0
To assess the tolerability of single and multiple doses of RB201 when administered by the oral route at escalating doses in healthy volunteers
Timepoint [2] 340926 0
SAD: Baseline, Day 1 (treatment day) through day 14. MAD: Baseline. Day 1 to Day 7 (treatment days) through day 21
Secondary outcome [1] 444854 0
To assess the pharmacokinetics (PK) of single and multiple doses of RB201 when administered by the oral route
Timepoint [1] 444854 0
Timepoints for pharmacokinetics (PK) for SAD are Predose, Day 1 (0.25 h, 0.5 h, 1 h, 2 h, 4 h, 8 h, 12 h), Day 2, Day 3, Day 4, and Day 7. Timepoints for SAD Food Effect PK are Predose, Day 1 and Day 4 (0.25 h, 0.5 h, 1 h, 2 h, 4 h, 8 h, 12 h), Day 2, Day 3, Day 5, Day 6, Day 7, and Day 14. Timepoints for MAD PK are Predose, Day 1 and Day 7 (0.25 h, 0.5 h, 1 h, 2 h, 4 h, 8 h, 12 h), Day 2, Day 4, Day 8, Day 9, and Day 14.
Secondary outcome [2] 444938 0
Exploratory: To assess the pharmacodynamics (PD) of single and multiple doses of RB201
Timepoint [2] 444938 0
Timepoints for pharmacodynamics (PD) for SAD are Predose, Day 1 (4 h), Day 2, and Day 7. Timepoints for MAD PD are Predose, Day 1 and Day 7 (4 h), Day 9, and Day 14.
Secondary outcome [3] 445477 0
Exploratory: To assess the relationship of pharmacodynamics (PD) of single and multiple doses of RB201 to PK. MALT1 has protease and scaffolding functions, and determining how the drug level influences these molecular functions and at what drug level they saturate is not a straightforward linear relationship. We will assess the relationships of PK to each PD through assays (proteolytic cleavage of target proteins, cytokine production, NFKB activation).
Timepoint [3] 445477 0
Timepoints for pharmacodynamics (PD) for SAD are Predose, Day 1 (Tmax), Day 2, and Day 7. Timepoints for MAD PD are Predose, Day 1 (Tmax) and Day 7 (accumulated), Day 9, and Day 14.

Eligibility
Key inclusion criteria
1. Is male or female, age 18 to 60 years, inclusive, at Screening.
2. Weight at Screening of greater than or equal to 40 kg and less than or equal to 120 kg
3. In good general health, determined by no clinically significant findings in the opinion of the Investigator from medical history, physical examination, 12-lead electrocardiogram (ECG), clinical laboratory findings, and vital signs at Screening and Check-in.
4. Hemoglobin, hematocrit, white blood cell count, absolute neutrophil count, absolute lymphocyte count, platelet count, ALT and AST results all not clinically significant as per the Investigator at the Screening Visit. Tests may be repeated at the discretion of the Investigator to confirm abnormalities.
5. Creatinine clearance based on the Cockcroft-Gault equation of greater than or equal to 80 mL/min.
6. Females of childbearing potential and males must practice effective contraception per national regulatory guidelines for clinical trials from Screening until 90 days after the EOS visit.
7. Females of childbearing potential must have a test confirming absence of pregnancy at Screening and within 24 hours prior to dosing of study drug; for putative post-menopausal subjects, a blood sample will also be tested for follicle stimulating hormone to confirm post-menopausal status.
8. Males must agree to not donate sperm for 90 days following the last dose of IP.
9. Able to provide Informed Consent.
10. Willing and able to comply with this protocol and be available for the entire duration of the study.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Any clinically significant underlying illness in the opinion of the Investigator.
2. Any history or sign of significant chronic active or recurrent infection, or screening laboratory evidence consistent with a significant chronic active or recurrent infection requiring treatment with antibacterials, antivirals, or antifungals.
3. Treatment of any infection with IV (within 30 days of Screening) or oral (within 14 days of Screening) antibacterials, antivirals, or antifungals.
4. History of clinically significant hematologic or bone marrow disease or blood dyscrasias.
5. History of latent tuberculosis that was not adequately treated as per guidelines
6. Prior exposure to RB201.
7. Positive serology for Hepatitis B core antigen, Hepatitis C virus, or HIV at Screening.
8. History of drug or alcohol abuse within 1 year of Screening in the opinion of the investigator, or a positive test for drugs of abuse or alcohol at Screening or Check-in.
9. Received any type of live attenuated vaccine < 1 month prior to Screening or is planning to receive any such live attenuated vaccine over the course of the study.
10. Use of any prescription or OTC medications, including food supplements, herbal medications (e.g., St. John’s wort), and cannabis, with the exception of contraceptive medications and as needed (prn) paracetamol (not exceeding 2 grams/day) within 7 days prior to IP administration.
11. History of malignancy, except adequately treated basal cell carcinoma or in situ carcinoma of the uterine cervix.
12. Smoking greater than 5 cigarettes per month in the 3 months prior to IP administration.
13. Any female who is pregnant or breastfeeding, or any female who is planning to become pregnant during the study and follow-up period.
14. Any condition that, in the investigator’s opinion, may compromise study participation, present a safety risk to the subject, or may confound the interpretation of the study results.
15. A QT duration corrected for heart rate by Fridericia's formula (QTcF) > 450 milliseconds (msec) for males and females based on either single or averaged QTcF values of triplicate ECGs obtained over a 3-minute interval (at Screening).
16. Currently enrolled in another investigational device or drug study, or less than 30 days or 5 half-lives of the prior investigational agent (whichever is longer) have passed since ending another investigational device or drug 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)
Paper-based randomisation with concealment
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation with fixed blocks
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Sequential groups based on escalating doses
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Summaries will be presented separately for SAD and MAD parts of the study, by dose level within study part, and overall within study part. For descriptive statistics, continuous data will be summarized by dose level and time point. Discrete data will be summarized using counts and percentages. PK samples will be collected at pre-specified timepoints for analysis of parameters including Cmax, Tmax, AUC, CL, and half life.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
3/03/2025
Date of last participant enrolment
Anticipated
5/07/2025
Actual
Date of last data collection
Anticipated
31/07/2025
Actual
Sample size
Target
88
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 318322 0
Commercial sector/Industry
Name [1] 318322 0
Rarefied Biosciences Australia PTY LTD
Country [1] 318322 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Rarefied Biosciences Australia PTY LTD
Address
Country
Australia
Secondary sponsor category [1] 320835 0
None
Name [1] 320835 0
Address [1] 320835 0
Country [1] 320835 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316957 0
Bellberry Human Research Ethics Committee L
Ethics committee address [1] 316957 0
Ethics committee country [1] 316957 0
Australia
Date submitted for ethics approval [1] 316957 0
18/12/2024
Approval date [1] 316957 0
17/02/2025
Ethics approval number [1] 316957 0
HREC2024-12-2113

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

Contacts
Principal investigator
Name 139562 0
Dr Christopher Argent
Address 139562 0
Scientia Clinical Research, Bright Building Corner High, Level 5 Avoca St, Randwick NSW 2031, Australia
Country 139562 0
Australia
Phone 139562 0
+61 2 9382 5800
Fax 139562 0
Email 139562 0
[email protected]
Contact person for public queries
Name 139563 0
Georgia Forrest
Address 139563 0
Scientia Clinical Research, Bright Building Corner High, Level 5 Avoca St, Randwick NSW 2031, Australia
Country 139563 0
Australia
Phone 139563 0
+61 1800 727 874
Fax 139563 0
Email 139563 0
[email protected]
Contact person for scientific queries
Name 139564 0
Georgia Forrest
Address 139564 0
Scientia Clinical Research, Bright Building Corner High, Level 5 Avoca St, Randwick NSW 2031, Australia
Country 139564 0
Australia
Phone 139564 0
+61 1800 727 874
Fax 139564 0
Email 139564 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No
No IPD sharing reason/comment: Aggregated data will be shared. Sharing individual data for a small trial of healthy volunteers does not offer scientific benefit. In addition, regulatory review of the trial data may limit access to individual data until the process is complete.



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.