Clinical trial NCT06260527: Safety and Pharmacokinetic Study of ARTS-011 in Chinese Healthy Volunteers
Official title: A Phase 1, Randomized, Double-blind, Third-party Open, Placebo-controlled Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Food Effect After Single and Multiple Oral Doses of ARTS-011 In Chinese Health Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chinese Healthy Volunteer
Lead sponsor: Allorion Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2024-02-15
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Single ascending dose (SAD) following by multiple ascending dose (MAD) and food effect study
Primary purpose: TREATMENT

Brief summary: This single- and multiple-ascending dose study is a Phase 1, first in human study of ARTS-011. The goal of the study is to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and food effect of ARTS-011 after single and multiple oral doses of ARTS-011 in Chinese healthy volunteers.

Detailed description: ARTS-011 is an oral potent Tyrosine kinase 2 (TYK2) inhibitor with a good selectivity profile over other human kinase. TYK2 is required for signal transduction and cellular functions downstream of interferons (IFN), IL-23, and IL-12 which are involved in the initiation and pathogenesis of psoriatic diseases. ARTS-011 is being developed for treatment of moderate-severe psoriasis and other autoimmune diseases.

Eligibility criteria: Inclusion Criteria:

* Healthy female and male subjects between the ages of 18 and 55 years.
* Body Mass Index (BMI) of 19.0 to 28.0 kg/m2; and a total body weight male ≥50.0 kg, female ≥45.0 kg.
* Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
* Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
* No evidence or history of clinically significant abnormalities of , vital signs (body temperature, pulse and blood pressure), laboratory tests (blood hematology and biochemistry, urine and coagulation function), 12-lead ECG and other examinations.
* Subjects has no fertility and sperm donation, egg donation plan and takes highly effective contraception during correctly for the duration of the active treatment period and for at least 90 days after the last dose of investigational drugs.

Exclusion Criteria:

* Evidence or history of clinically significant hematological, renal, endocrine pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
* Any condition possibly affecting drug absorption (eg, gastrectomy).
* A positive urine drug screen.
* History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1 drink = 150 mL) of wine or 360 mL of beer or 45 mL of hard liquor within 3 months of screening.
* History of tobacco/nicotine containing products in excess of \>5 cigarettes/day within 3 months of screening.
* Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of investigational product, whichever is longer.
* 12-lead ECG demonstrating QTc \>450, or a QRS interval \>120 msec at Screening. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTc (or QRS) values should be used to determine the subject's eligibility.
* Screening laboratory abnormalities as defined by the protocol.
* Unwilling or unable to comply with the Lifestyle Guidelines as defined by the protocol.
* Subjected is not appropriate to be enrolled in the study per investigator's assessment.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs) and Discontinuation Due to AEs
timeFrame: SAD Cohort: Baseline up to Day 8, MAD Cohort: Baseline up to Day 14, Food Effect Cohort: Baseline up to Day 15
measure: Number of Adverse Events (AEs) according to severity
timeFrame: SAD Cohort: Baseline up to Day 8, MAD Cohort: Baseline up to Day 14, Food Effect Cohort: Baseline up to Day 15
measure: Number of participants with change from baseline in vital signs (blood pressure, pulse rate, oral temperature)
timeFrame: SAD Cohort: Baseline up to Day 8, MAD Cohort: Baseline up to Day 14, Food Effect Cohort: Baseline up to Day 15
measure: Number of participants with change from baseline in 12-Lead Parameters (PR Interval, QRS Complex, QT Interval, QTC Interval)
timeFrame: SAD Cohort: Baseline up to Day 8, MAD Cohort: Baseline up to Day 14, Food Effect Cohort: Baseline up to Day 15
measure: Number of participants with change from baseline physical examination
timeFrame: SAD Cohort: Baseline up to Day 8, MAD Cohort: Baseline up to Day 14, Food Effect Cohort: Baseline up to Day 15
measure: Incidence and magnitude of treatment emergent clinical laboratory abnormalities
timeFrame: SAD Cohort: Baseline up to Day 8, MAD Cohort: Baseline up to Day 14, Food Effect Cohort: Baseline up to Day 15
measure: Number of participants with change in 24-hour creatine clearance from baseline
timeFrame: SAD Cohort: Baseline and Day 1, MAD Cohort: Baseline and Day 7
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of ARTS-011 in Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD)
timeFrame: SAD: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours postdose on Day 1; MAD: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 and Day 7
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of ARTS-011 in Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD)
timeFrame: SAD: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours postdose on Day 1; MAD: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 and Day 7
measure: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of ARTS-011 in Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD)
timeFrame: SAD: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours postdose on Day 1; MAD: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 and Day 7
measure: Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last) of ARTS-011 in Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD)
timeFrame: SAD: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours postdose on Day 1; MAD: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 and Day 7
measure: Plasma Decay Half-Life (t1/2) of ARTS-011 in Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD)
timeFrame: SAD: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours postdose on Day 1; MAD: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 and Day 7
measure: Apparent Volume of Distribution (Vz/F) of ARTS-011 in Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD)
timeFrame: SAD: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours postdose on Day 1; MAD: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 7
measure: Apparent Clearance (CL/F) of ARTS-011 in Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) if data permit
timeFrame: SAD: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours postdose on Day 1; MAD: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 7
measure: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of ARTS-011 in Single Ascending Dose (SAD)
timeFrame: SAD: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours postdose on Day 1
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of ARTS-011 in Multiple Ascending Dose (MAD)
timeFrame: MAD: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 7
measure: Dose Normalized Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf[dn]) of ARTS-011 in Single Ascending Dose (SAD)
timeFrame: SAD: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours postdose on Day 1
measure: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau[dn]) of ARTS-011 in Multiple Ascending Dose (MAD)
timeFrame: MAD: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 7
measure: Maximum Observed Plasma Concentration (Cmax) of ARTS-011 in Food Effect Cohort
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 and Day 8
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of ARTS-011 in Food Effect Cohort
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 and Day 8
measure: Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last) of ARTS-011 in Food Effect Cohort
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 and Day 8
measure: Plasma Decay Half-Life (t1/2) of ARTS-011 in Food Effect Cohort
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 and Day 8
measure: Apparent Clearance (CL/F) of ARTS-011 in Food Effect Cohort if data permit
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 and Day 8
measure: Apparent Volume of Distribution (Vz/F) of ARTS-011 in Food Effect Cohort if data permit
timeFrame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 and Day 8
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
Study officials:
affiliation: Beijing Friendship Hospital, Capital Medical University, China
name: Ruihua Dong, MD
role: PRINCIPAL_INVESTIGATOR
References: