RecruitingPhase 1ACTRN12625000694415

First-time-in-human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RB201 in Healthy Adult Subjects

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

Sponsor

Rarefied Biosciences Australia PTY LTD

Enrollment

88 participants

Start Date

Mar 3, 2025

Study Type

Interventional

Conditions

autoimmunity

Summary

RB201 is being developed by Rarefied Biosciences for the treatment of autoimmune diseases. We hypothesize that this new drug, which is being tested for the first time in healthy volunteers, may adjust the body’s immune system in a way that could help reduce the inflammation of autoimmune diseases. This study (RB201-001) is a randomized, double-blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of escalating single and multiple doses of RB201 in healthy volunteers. This study will be conducted in 2 parts: Single ascending dose and Multiple ascending doses. Up to 88 healthy volunteer subjects total will be entered into the study. RB201 or matching placebo will be administered orally in an observed, inpatient setting to help us learn how the drug behaves in the body, how safe it is, and whether it has any side effects.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 60 Yearss

Inclusion Criteria10

Is male or female, age 18 to 60 years, inclusive, at Screening.
Weight at Screening of greater than or equal to 40 kg and less than or equal to 120 kg
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.
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.
Creatinine clearance based on the Cockcroft-Gault equation of greater than or equal to 80 mL/min.
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.
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.
Males must agree to not donate sperm for 90 days following the last dose of IP.
Able to provide Informed Consent.
Willing and able to comply with this protocol and be available for the entire duration of the study.

Exclusion Criteria16

Any clinically significant underlying illness in the opinion of the Investigator.
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.
Treatment of any infection with IV (within 30 days of Screening) or oral (within 14 days of Screening) antibacterials, antivirals, or antifungals.
History of clinically significant hematologic or bone marrow disease or blood dyscrasias.
History of latent tuberculosis that was not adequately treated as per guidelines
Prior exposure to RB201.
Positive serology for Hepatitis B core antigen, Hepatitis C virus, or HIV at Screening.
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.
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.
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.
History of malignancy, except adequately treated basal cell carcinoma or in situ carcinoma of the uterine cervix.
Smoking greater than 5 cigarettes per month in the 3 months prior to IP administration.
Any female who is pregnant or breastfeeding, or any female who is planning to become pregnant during the study and follow-up period.
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.
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).
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.

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Interventions

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,

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.