A Phase I Study of QLS12010 Capsules: Safety, Tolerability, PK, PD, and Food Effects in Healthy Adults and Moderate to Severe Atopic Dermatitis Patients

Shanghai Qilu Pharmaceutical Research and Development Center LTD

Status and phase: Enrolling; Phase 1

Conditions: Atopic Dermatitis; Rheumatoid Arthritis (RA); Hidradenitis Suppurativa (HS)

Treatments: Drug: Placebo; Drug: QLS12010

Study type: Interventional

Funder types: Industry

Identifiers

NCT06946641

QLS12010-101

Details and patient eligibility

About

The goal of this clinical trial is to evaluate the safety, tolerability, PK, and PD of single and multiple ascending doses of QLS12010 Capsules and the effect of food on their PK profiles in healthy adult participants and participants with atopic dermatitis. This study consists of four parts: Part A is a single ascending dose (SAD) study, once sufficient safety and PK data are obtained from the SAD cohorts, the SMC will determine the dosage of initial cohort in Part B, which consists of three multiple ascending doses (MAD) cohorts of QLS12010 Capsules. Part C is a randomized, open-label, two-cycle, crossover food effect study under fasting and fed (high-fat meal) conditions. Part D is to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) characteristics, and preliminary efficacy of QLS12010 Capsules following multiple oral administrations in adult participants with atopic dermatitis (AD).

Enrollment: 102 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria for Parts A-C:

• Males and females aged 18-45 (inclusive),
• Weight: ≥ 50 kg for males and ≥ 45 kg for females, body mass index (BMI): 18.0-30.0 kg/m2 (inclusive),

Inclusion Criteria for Part D:

• Female or male participants between the ages of 18 to 75 years of age.
• Chronic AD diagnosed by the criteria of Hannifin and Rajka that has been present for at least 6 Months before the Screening Visit.
• At screening and baseline: EASI score ≥ 16, vIGA-AD™ score ≥ 3, and BSA affected by AD ≥ 10%;
• The weekly mean score of PP NRS ≥ 4 prior to the first administration (with assessment results for at least 4 days during the week before the first administration [D-7 to D-1]);
• As judged by the investigator, within 6 months prior to screening, the patient had an inadequate response to topical medication therapy.

General Exclusion Criteria:

• Participants with diseases that should be excluded as judged by the investigator at screening, including but not limited to the nervous system, psychiatric system, cardiovascular system, blood and lymphatic system, immune system, respiratory system, digestive system, urinary system, metabolic and skeletal system disorders,
• The 12-lead ECG at screening shows QTcF (QT corrected using Fridericia's formula) > 450 ms. If QTcF is > 450 ms, the 12-lead ECG should be repeated 2 more times (at least 3 min apart), and the mean of the 3 measurements will be used to determine whether the participant meets the inclusion criteria,
• Participants who smoke more than 5 cigarettes per day on average within 6 months before screening or are currently using e-cigarettes,
• Participants who consume more than 14 units of alcohol per week (1 unit = 360 mL of beer, 45 mL of 40% spirits, or 150 mL of wine) within 6 months before screening or have a positive breath alcohol test at screening,
• Participants who have donated more than 400 mL of blood within 3 months or more than 200 mL of blood within 4 weeks before screening, or plan to donate blood during the study,
• Participants who have received any strong inhibitor or inducer of CYP3A4 within 4 weeks before screening,
• Participants who have received any prescription drugs, OTC drugs, traditional medicines, and dietary supplements within 2 weeks before the first dose or 5 half-lives (whichever is longer).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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102 participants in 4 patient groups

Single ascending dose cohorts in healthy participants

Experimental group

Description:

Healthy volunteer subject cohorts randomized 6:2 receiving a single dose of QLS12010 or placebo. The starting dose will be 25 mg of QLS12010 or placebo.

Treatment:

Drug: QLS12010

Drug: Placebo

Multiple ascending dose cohorts in healthy subjects

Experimental group

Description:

Healthy volunteer subject cohorts randomized 8:2 to receive QLS12010 or placebo QD for 14 continuous days. The starting dose of QLS12010 or placebo is based on upcoming data from SAD part.

Treatment:

Drug: QLS12010

Drug: Placebo

Food Effect Cohort in healthy subjects

Experimental group

Description:

Part C is a two-cycle, crossover study under fasting and fed (high-fat meal) conditions. In Cycle 1, 12 healthy adult participants will be randomly divided into two groups on D-1, with 6 participants in each group receiving a single oral dose of QLS12010 Capsules under fasting or fed conditions, respectively. After completing washout, they will receive crossover administration for the Cycle 2 study.

Treatment:

Drug: QLS12010

Early Efficacy in patients with AD

Experimental group

Description:

Part D of the study plans to enroll 12 adults with moderate to severe atopic dermatitis (AD). Eligible subjects (after screening) will be sequentially assigned to two dose groups (Dose 1 and Dose 2) in the order of their enrollment. Enrollment of Dose 2 may commence only after Dose 1 has completed enrollment of 6 subjects.

Treatment:

Drug: QLS12010