A Study of Single and Multiple Ascending Doses of H021 in Healthy Participants

A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of H021 in Healthy Participants

The primary purpose of this study is to evaluate the safety and tolerability of H021 tablets following oral administration of single and multiple ascending doses in healthy participants.

Study Overview

• Status: Recruiting
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: H021; Drug: H021 Placebo

Detailed Description

This is a single center, Phase 1, randomized, double-blind, placebo controlled, sequential single ascending dose/multiple ascending dose (SAD/MAD) study, with a food-effect arm. The study will be divided into two parts:

• SAD cohorts, with food-effect evaluation
• MAD cohorts The two parts will be completed sequentially but with partial overlapping. The MAD phase can start once safety, tolerability, and pharmacokinetic data from the SAD phase show that single doses of at least 25 mg are acceptable. If the 25 mg dose will be not reached in the SAD phase, the Safety Review Committee (SRC) will set a new starting dose.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Dr. Ofer Gonen; Phone Number: 0385939801; Email: o.gonen@nucleusnetwork.com.au

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Nucleus Network Ply Ltd.
      • Contact: Ofer Gonen; Phone Number: 0385939801; Email: o.gonen@nucleusnetwork.com.au
      • Contact: Dr. Ofer Gonen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male or female, non-smoker (no use of tobacco or nicotine products within 3 months prior to screening), greater than and equal to (>=) 18 and less than and equal to (<=) 55 years of age, with body mass index (BMI) greater than (>)18.5 and less than (<) 32.0 kilograms per square meter (kg/m^2).

2. Healthy as defined by:

   1. the absence of clinically significant illness and surgery within 4 weeks prior to study drug administration.
   2. the absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.

3. Female participants of non-childbearing potential must be:

   1. post-menopausal (spontaneous amenorrhea for at least 12 months prior to dosing) with confirmation by documented follicle-stimulating hormone (FSH) levels >=40 milli-international units per milliliter (mIU/mL); or
   2. surgically sterile (bilateral oophorectomy, bilateral salpingectomy, hysterectomy, or bilateral tubal occlusion) at least 3 months prior to dosing.
4. Participants must be willing not to donate sperm for 90 days or ova (egg) for 6 months after the last dose.
5. Sexually active females of childbearing potential and non-sterile males must be willing to use an acceptable contraceptive method throughout the study.
6. Able to understand the study procedures and provide signed informed consent to participate in the study.

Exclusion Criteria:

1. Any clinically significant abnormal finding at physical examination.
2. Clinically significant abnormal laboratory test results including biochemistry, hematology, urinalysis, and coagulation results, or positive serology test results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen and antibody, or QuantiFERON®-TB test at screening.
3. Positive pregnancy test or lactating female participant.
4. Positive urine drug screen, urine cotinine test, or alcohol breath test at screening or Day -1.
5. History of significant allergic reactions (example, anaphylactic reaction, hypersensitivity, angioedema) to any drug.
6. Clinically significant ECG abnormalities or vital signs abnormalities (systolic blood pressure lower than 90 or over 140 millimetres of mercury (mmHg), diastolic blood pressure lower than 40 or over 90 mmHg, heart rate less than 40 or over 100 beats per minute (bpm), respiratory rate less than 10 or over 22 bpm), or oxygen saturation less than 95 percent (%) oxygen at screening.
7. History of drug abuse within 1 year prior to screening as determined by the investigator.
8. History of alcohol abuse within 1 year prior to screening or regular use of alcohol within 1 month prior to screening that exceeds 10 units of alcohol per week for women and men (1 unit = 375 [milliliter] mL of beer 3.5%, 100 mL of wine 13.5%, or 30 mL of distilled alcohol 40%).
9. History of active tuberculosis or presence of active or latent tuberculosis. Previous latent tuberculosis that has been treated and is no longer active is not exclusionary.
10. History of clinically significant opportunistic infection (example, invasive candidiasis or pneumocystis pneumonia).
11. History of serious local infection (example, cellulitis, abscess) or systemic infection (example, septicemia) within 3 months prior to screening.
12. Presence of fever (body temperature greater than (>) 37.5 degrees Celsius (°C) (example, a fever associated with a symptomatic viral or bacterial infection) within 2 weeks prior to dosing.
13. Use of medications within the timeframes specified.
14. Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or simultaneous participation in an investigational study involving no drug or device administration.
15. Donation of plasma within 7 days prior to dosing or donation or loss of 500 mL or more of whole blood within 8 weeks prior to dosing.
16. Any reason which, in the opinion of the Investigator, would prevent the participant from participating in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAD Cohort 1: H021 6.25 milligrams (mg); Participants will receive H021, 6.25 mg oral tablet, as single-dose on Day 1 under fasting or fed conditions.	Drug: H021; H021 oral tablet.
Experimental: SAD Cohort 2: H021 12.5 mg; Participants will receive H021, 12.5 mg oral tablet, as single-dose on Day 1 under fasting conditions.	Drug: H021; H021 oral tablet.
Experimental: SAD Cohort 3: H021 25 mg; Participants will receive H021, 25 mg oral tablet, as single-dose on Day 1 under fasting conditions.	Drug: H021; H021 oral tablet.
Experimental: SAD Cohort 4: H021 50 mg; Participants will receive H021, 50 mg oral tablet, as single-dose on Day 1 under fasting conditions.	Drug: H021; H021 oral tablet.
Experimental: SAD Cohort 5: H021 100 mg; Participants will receive H021, 100 mg oral tablet, as single-dose on Day 1 under fasting conditions.	Drug: H021; H021 oral tablet.
Experimental: MAD Cohort 6: H021 12.5 mg; Participants will receive H021, 12.5 mg oral tablet once daily from Day 1 to Day 7 under fasting conditions.	Drug: H021; H021 oral tablet.
Experimental: MAD Cohort 7: H021 25 mg; Participants will receive H021, 25 mg oral tablet once daily from Day 1 to Day 7 under fasting conditions.	Drug: H021; H021 oral tablet.
Experimental: MAD Cohort 8: H021 50 mg; Participants will receive H021, 50 mg oral tablet once daily from Day 1 to Day 7 under fasting conditions.	Drug: H021; H021 oral tablet.
Placebo Comparator: SAD-H021 Placebo; Participants will receive H021, placebo oral tablet, as single-dose on Day 1 under fasting or fed conditions.	Drug: H021 Placebo; H021 placebo oral tablet.
Placebo Comparator: MAD-H021 Placebo; Participants will receive H021, placebo oral tablet once daily from Day 1 to Day 7 under fasting conditions.	Drug: H021 Placebo; H021 placebo oral tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs)	An AE is defined as any untoward medical occurrence in a participant or clinical trial participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. Any clinically significant changes in vital signs, electrocardiogram (ECG) measurement, physical examination and clinical laboratory parameters will be recorded as AE.	Up to final follow-up (SAD Part: up to 8 days: MAD Part: up to 14 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SAD Part: Area under the concentration-time curve from time zero until the last observed concentration (AUC0-t) of H021	AUC0-t is an area under the concentration-time curve from time zero (pre-dose) to time of last observed concentration.	pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours post-dose
SAD Part: Area under the concentration-time curve from time zero to infinity (AUC0-infinity) of H021	AUC0-infinity is an area under the concentration-time curve from time zero to infinity (extrapolated).	pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours post-dose
SAD Part: Maximal observed concentration (Cmax) of H021	Cmax is a measure of the maximum amount of drug in the plasma after the dose was given.	pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours post-dose
SAD Part: Time to Reach Cmax (Tmax) of H021	Tmax is a measure of the time to reach the maximum concentration in the plasma after the dose was given.	pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours post-dose
SAD Part: Lag Time (Tlag) of H021	Tlag is time of observation prior to the first observation with a measurable (non-zero) concentration (for food effect cohort only).	pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours post-dose
SAD Part: Residual area of H021	Residual area is calculated as percentage of AUC0-inf due to extrapolation from the time of the last observed concentration to infinity, calculated as [1 - (AUC0-t/AUC0-inf)] x 100.	pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24), and 48 hours post-dose
SAD Part: Terminal elimination half-life (T1/2 el) of H021	T1/2 el is defined as the duration until observation of half of the maximum concentration of drug dose.	pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours post-dose
SAD Part: Terminal elimination rate constant (Kel) of H021	Kel is defined as first-order rate constant associated with the terminal (log-linear) portion of the curve.	pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours post-dose
SAD Part: Apparent clearance (CL/F) of H021	CL/F is apparent total clearance of the drug from plasma after oral administration	pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours post-dose
SAD Part: Apparent volume of distribution (Vz/F) of H021	Vz/F is apparent volume of distribution during terminal phase after non-intravenous administration	pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours post-dose
SAD Part: Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) of H021	Ae0-t is defined as cumulative urinary excretion from time zero to time t, calculated as the sum of the amounts excreted over each collection interval.	pre-dose (spot; within 2 hours) and 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose
SAD Part: Maximal Rate of Urinary Excretion (Rmax) of H021	Rmax is defined as maximal rate of urinary excretion, calculated by dividing the amount of drug excreted in each collection interval by the time over which it was collected.	pre-dose (spot; within 2 hours) and 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose
SAD Part: Time of Maximal Urinary Excretion (TRmax) of H021	TRmax is defined as time of maximal urinary excretion, calculated as the midpoint of the collection interval during which Rmax occurred.	pre-dose (spot; within 2 hours) and 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose
SAD Part: Renal Clearance (CLR) of H021	CLR is renal clearance, calculated as Ae0-t /AUC0-t.	pre-dose (spot; within 2 hours) and 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose
MAD Part: Area under the concentration-time curve from time zero to time 24 hours (AUC0-24) of H021	AUC0-24 is an area under the concentration-time curve from time zero to 24 hours post-dose.	Day 1 at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-first dose; predose on Days 4, 5, 6; Day 7 at predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-last dose
MAD Part: Cmax of H021	Cmax is a measure of the maximum amount of drug in the plasma after the dose was given.	Day 1 at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-first dose; predose on Days 4, 5, 6; Day 7 at predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-last dose
MAD Part: Tmax of H021	Tmax is a measure of the time to reach the maximum concentration in the plasma after the dose was given.	Day 1 at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-first dose; predose on Days 4, 5, 6; Day 7 at predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-last dose
MAD Part: Area under the concentration-time curve for one dosing interval (τ) at steady- state (AUC0-τ) of H021	AUC0-τ is an area under the concentration-time curve for one dosing interval (τ) at steady- state. In this study τ = 24 hours (equivalent to AUC0-24) will be reported.	Day 1 at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-first dose; predose on Days 4, 5, 6; Day 7 at predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-last dose
MAD Part: Cmax ss of H021	Cmax ss is a measure of the maximum amount of drug in the plasma at steady-state after the dose was given.	Day 1 at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-first dose; predose on Days 4, 5, 6; Day 7 at predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-last dose
MAD Part: Tmax ss of H021	Tmax ss is a measure of the time to reach the maximum concentration in the plasma at steady state after the dose was given.	Day 1 at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-first dose; predose on Days 4, 5, 6; Day 7 at predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-last dose
MAD Part: Minimal observed concentration at steady-state (Cmin ss) of H021	Cmin ss is minimal observed concentration at steady-state.	Day 1 at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-first dose; predose on Days 4, 5, 6; Day 7 at predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-last dose
MAD Part: AUC0-t of H021	AUC0-t is an area under the concentration-time curve from time zero (pre-dose) to time of last observed concentration.	Day 1 at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-first dose; predose on Days 4, 5, 6; Day 7 at predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-last dose
MAD Part: AUC0-inf of H021	AUC0-infinity is an area under the concentration-time curve from time zero to infinity (extrapolated).	Day 1 at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-first dose; predose on Days 4, 5, 6; Day 7 at predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-last dose
MAD Part: Residual area of H021	Residual area is calculated as percentage of AUC0-inf due to extrapolation from the time of the last observed concentration to infinity, calculated as [1 - (AUC0-t/AUC0-inf)] x 100.	Day 1 at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-first dose; predose on Days 4, 5, 6; Day 7 at predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-last dose
MAD Part: T½ el of H021	T1/2 el is defined as the duration until observation of half of the maximum concentration of drug dose.	Day 1 at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-first dose; predose on Days 4, 5, 6; Day 7 at predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-last dose
MAD Part: Kel of H021	Kel is defined as first-order rate constant associated with the terminal (log-linear) portion of the curve.	Day 1 at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-first dose; predose on Days 4, 5, 6; Day 7 at predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-last dose
MAD Part: Apparent clearance at steady-state (Clss/F) of H021	Clss/F is apparent clearance at steady-state.	Day 1 at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-first dose; predose on Days 4, 5, 6; Day 7 at predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-last dose
MAD Part: Apparent volume of distribution at steady-state (Vz ss/F) of H021	Vz ss/F is apparent volume of distribution at steady-state.	Day 1 at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-first dose; predose on Days 4, 5, 6; Day 7 at predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-last dose
MAD Part: Accumulation ratio (RAUC)	RAUC is accumulation ratio for AUC.	Day 1 at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-first dose; predose on Days 4, 5, 6; Day 7 at predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-last dose
MAD Part: Accumulation Ratio (RCmax)	RCmax is accumulation ratio for Cmax.	Day 1 at pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-first dose; predose on Days 4, 5, 6; Day 7 at pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours post-last dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
MAD Part: Change From Baseline in Micro-RNA-124 (miR-124) Expression in Peripheral Blood Mononuclear Cells (PBMCs)	Change from baseline in miR-124 expression in PBMCs will be assessed.	Day 1 at predose, and at 12 hours, on Day 5 at predose, and on Day 7 at predose, and at 12 hours post-last dose
MAD Part: Change From Baseline in Interleukin (IL)-6, Tumor Necrosis Factor Alpha (TNF-α), IL-17A, and Interferon Gamma (IFN-γ) in Blood Serum	Change from baseline in IL-6, TNF-α, IL-17A, and IFN-γ in blood serum will be assessed.	Day 1 at predose, and at 12 hours, on Day 5 at predose, and on Day 7 at predose, and at 12 hours post-last dose

Collaborators and Investigators

• Sponsor: Jiangsu Carephar Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2024
• Primary Completion (Estimated): February 27, 2025
• Study Completion (Estimated): February 27, 2025

Study Registration Dates

• First Submitted: October 3, 2024
• First Submitted That Met QC Criteria: October 3, 2024
• First Posted (Actual): October 4, 2024

Study Record Updates

• Last Update Posted (Actual): October 4, 2024
• Last Update Submitted That Met QC Criteria: October 3, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: KFP-2024-H021-HW-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No