SAD/MAD Safety and PK Study of RBN-3143 in Healthy and Atopic Dermatitis Subjects

Atopic Dermatitis Clinical Trial

Official title: A First-in-Human, Randomized, Placebo-Controlled, Phase 1 Single and Multiple Ascending Dose Study to Assess the Safety and Pharmacokinetics of RBN-3143 in Healthy Subjects and as Open-Label in Patients With Atopic Dermatitis Subjects

Status Recruiting

Clinical Trial Summary

RBN-3143 Background: PARP proteins are members of a family of seventeen ADP-ribosyltransferase (ART) enzymes that regulate cellular processes including gene expression, protein degradation, and multiple cellular stress responses. RBN-3143 is a PARP-14 inhibitor. PARP14 is over-expressed in tissues with inflammatory diseases. RBN-3143 is a novel, orally administered PARP14 inhibitor that was developed to be evaluated as therapy for a range of inflammatory diseases, with an initial focus on Atopic Dermatitis.

Study Overview: The study consists of 2 parts. Part A: This part of the study is being conducted in a clinical research unit (CRU) and is enrolling healthy adult subjects to determine the safety of RBN-3143; its absorption, metabolism, and excretion (what the body does to this drug); and will assess its potential pharmacodynamic properties (what the drug does to the body).

There are 3 subsections to this part of the study. The first segment was conducted in a double-blind manner (neither the investigator nor subject knew if placebo or RBN-3143 was given) to assess dosing regimens of RBN-3143 when taken in a fasted state (before food). The last two segments are currently recruiting and are Open Label (all subjects will receive RBN-3143) and will assess RBN-3143 when taken with food, with pantoprazole, a medication that decreases the amount of acid in the stomach, and with midazolam.

Part B: In early 2023 the second part of the study will be conducted in patients with moderate to severe atopic dermatitis to measure the pharmacodynamic activity of RBN-3143 and evaluate preliminary efficacy of 28 days administration of the study drug. All patients will receive the same dose of RBN-3143.

Clinical Trial Description

The study consists of 2 parts.

Part A: This part of the study is being conducted in a clinical research unit (CRU) and will enroll healthy adult subjects to determine the safety of RBN-3143; its absorption, metabolism, and excretion (what the body does to this drug); and will assess its potential pharmacodynamic properties (what the drug does to the body).

There are 3 subsections to this part of the study. The first subsection has completed enrollment and the 2 open-label subsections are now actively enrolling.

1. Double-Blind Cohorts- Fasting: In the first segment of the study, subjects were randomized in a double-blind manner using a 3:1 ratio (RBN-3143: placebo) to receive either RBN-3143 or placebo. Subjects were enrolled in groups of ascending doses.

2. Open Label Cohorts:

1. Food Effect/Proton Pump Inhibitor (FE/PPI) Open Label Cohort:

Twelve (12) additional subjects are being enrolled and will receive RBN-3143 with food (fed), fasted, or with pantoprazole, PPI, a drug to determine if the amount of acid in the stomach, as well as the presence or absence of food changes how RBN-3143 is absorbed. Subjects will be required to stay in the CRU for up to 16 days. Two sequences will be studied, either fasted then fed or fed then fasted with both sequences followed by administration of a proton pump inhibitor.

2. Drug-Drug Interaction (DDI) Open Label Cohort: A further 12 subjects are being enrolled into a DDI cohort, to evaluate the effect of RBN-3143 on the exposure of midazolam, a sensitive CYP3A4 substrate. Subjects will be required to stay in the CRU 19 days. Subjects will also return for a final visit approximately 1 week later. This cohort will have 2 Treatment Periods as follows:

• Treatment Period 1: On Day 1, subjects will be administered a single oral dose of 2 mg midazolam in the fasted state.

• Treatment Period 2: Subjects will be administered RBN-3143 in the fasted state from Day 3 through Day 17 (14- day treatment period). On Day 16, subjects will also receive a single oral dose of 2 mg midazolam in the fasted state.

Part B: In early 2023 the second part of the study will be initiated in approximately 12 patients with moderate to severe atopic dermatitis. All patients will receive the same doses of RBN-3143 for 28 days.

On Day 1 and Day 28 patients will fast overnight until after the morning dose administration then fast for 4 hours post-dose. On all other days fasted state will be 2 hours prior to dosing and 2 hours after dosing. Patients will be required to present at the CRU on Day -1 for required study assessments after which they may return home. Patients will return to the CRU on Day 1 for the day 1 dose and the completion of required study assessments. Patients will then return home with sufficient study drug to complete dosing on Days 2 to Day 27 (inclusive). Patients will be required to attend the CRU for completion of required assessments on Day 7, Day 14, Day 21, and Day 28, and will return any remaining study drug on the Day 28 visit. Patients will return for an EOS/Follow-up visit at 4 weeks after the last dose of study drug.

Collection of data will cease at the time of database lock for final safety and PK analysis. ;

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

• NCT number: NCT05215808
• Study type: Interventional
• Source: Ribon Therapeutics, Inc.
• Contact: Clinical Operations Manager
• Phone: 617-914-8596
• Email: clinicaltrials@ribontx.com
• Status: Recruiting
• Phase: Phase 1
• Start date: March 7, 2022
• Completion date: September 30, 2024