Phase 1 Study of QX-4533 in Healthy Volunteers and Patients With Moderate-to-Severe Atopic Dermatitis

A Phase 1 Study With a Single Ascending Dose-escalation in Healthy Volunteers to Assess the Safety, Tolerability, and Pharmacokinetics of QX-4533 and a Randomized, Double-Blind, Placebo-Controlled, Parallel Group to Assess the Safety, Pharmacokinetics, and Preliminary Efficacy of QX-4533 in Participants With Moderate-to-Severe Atopic Dermatitis

The goal of this clinical trial is to evaluate the safety and tolerability of QX-453, an investigational treatment, in healthy Chinese volunteers and patients with moderate-to-severe atopic dermatitis. The study will assess how the drug is absorbed and processed by the body, and check for any side effects. Participants will receive single or repeated oral doses of QX-453 under close medical supervision, with regular safety and clinical assessments throughout the trial.

Inclusion Criteria:

- Part 1: Eligibility Criteria for HVs

Inclusion criteria:

Participants are eligible to be included in Part 1 of the study only if all of the following criteria apply:

1. Fully understanding the purpose, nature, method, and possible adverse reactions of the trial, voluntarily participating as a clinical trial participant, and signing the ICF;
2. Being willing and able to comply with the study protocol and cooperate in completing the visit procedures throughout the study;
3. Males and females aged 18 to 55 years (inclusive, at the time of signing the ICF) at screening;
4. Body mass index (BMI) of 18 to 28 kg/m2 (inclusive); weight not less than 50 kg for male and 45 kg for female;
5. Participants in good general health as judged by the Investigator based on their medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory findings (normal or abnormal but not clinically significant) at screening and on Day -1;
6. Female participants must be non-pregnant and non-lactating, and female participants of childbearing potential must agree to use contraception from the signing of the ICF until at least 40 days after the last dose (10 days [approximately 5 t1/2] plus 30 days). Male participants with female partners of childbearing potential must agree to use contraception from the signing of the ICF until at least 100 days after the last dose (10 days [approximately 5 t1/2] plus a 90-day spermatogenesis cycle) (by taking medically approved effective contraceptive measures. See Appendix 3 Contraceptive Measures and Definition of Women of Childbearing Potential for details). Male participants must refrain from donating sperm for at least 150 days after the last dose. Female participants must refrain from donating eggs for at least 40 days after the last dose.

Part 2: Eligibility Criteria for Participants with AD Inclusion Criteria

Participants are eligible to be included in Part 2 of the study only if all of the following criteria apply:

1. Fully understanding the purpose, nature, method, and possible adverse reactions of the trial, voluntarily participating as a participant, and signing the ICF;
2. Being willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures and questionnaires, including completing the electronic diaries and questionnaires, for the duration of the study as required by the study protocol;
3. Males and females aged 18 to 65 years (inclusive) at screening;
4. Participants with chronic AD diagnosed by the Eichenfield revised criteria of Hannifin and Rajka and with a confirmed diagnosis for at least one year prior to the screening visit;
5. Participants with inadequate response, intolerance, or contraindication to topical corticosteroids and/or topical calcineurin inhibitors;
6. Participants must be able and willing to regularly use a mild, inactive ingredient-free emollient twice daily for at least 7 consecutive days before randomization and continue to use it during the study;
7. Female participants must be non-pregnant and non-lactating, and female participants of childbearing potential must agree to use contraception from the signing of the ICF until at least 40 days after the last dose (10 days [approximately 5 t1/2] plus 30 days). Male participants with female partners of childbearing potential must agree to use contraception from the signing of the ICF until at least 100 days after the last dose (10 days [approximately 5 t1/2] plus a 90-day spermatogenesis cycle) (by taking medically approved effective contraceptive measures. See Appendix 3 Contraceptive Measures and Definition of Women of Childbearing Potential for details). Male participants must refrain from donating sperm for at least 150 days after the last dose. Female participants must refrain from donating eggs for at least 40 days after the last dose.

Exclusion Criteria:

Part 1:

1. Participants who are mentally or legally incapacitated, have a history of psychosis, or have significant emotional or psychological problems at the time of the study according to the Investigator;
2. Participants with dysphagia, oesophageal stenosis, or gastrointestinal diseases that cause clinically significant symptoms such as nausea, vomiting, diarrhoea, or malabsorption syndrome, or with a history of severe vomiting or diarrhoea within one week before the screening period;
3. Participants who have previously undergone surgeries that the Investigator deems may affect drug absorption, distribution, metabolism, or excretion (e.g., gastrectomy, cholecystectomy, gastric bypass, duodenal resection, colectomy);
4. Participants with a history of any ongoing medical condition requiring treatment with prescription medication within two weeks prior to screening;
5. Participants with a history of any infection requiring treatment with a prescription anti-infective in the past 4 weeks prior to screening;
6. Use of any prescription medications, health supplements, herbal supplements, traditional Chinese medicines (TCMs), Chinese patent medicines, or over-the-counter (OTC) medications (except for routine vitamin supplements) within two weeks prior to dosing;
7. Participants with history of malignancy, except fully resolved basal cell carcinoma (BCC), squamous cell carcinoma (SCC), or in situ carcinoma of the uterine cervix;
8. History of invasive, opportunistic infections such as histoplasmosis, listeriosis, coccidioidomycosis, candidiasis, Pneumocystis jirovecii pneumonia, and aspergillosis (including resolved cases); John Cunningham (JC) virus (progressive multifocal leukoencephalopathy), or any active or parasitic infection in the prior 30 days;
9. Participants who have undergone surgery, experienced significant blood loss, or donated more than one unit of whole blood (200 mL) within 8 weeks prior to screening, or who have donated more than one unit of plasma (100 mL) within 7 days prior to screening, or who plan to donate blood during the trial;
10. Participants who have smoked more than 10 cigarettes (or equivalent nicotine-containing products) per week on average within 90 days prior to screening and are unwilling to quit smoking during hospitalization or restrict smoking to no more than 10 cigarettes (or equivalent nicotine-containing products) per week during the post-discharge period;
11. Participants who have consumed more than 14 units of alcohol per week (1 unit = 360 mL of beer; 150 mL of wine; 45 mL of spirits) within 90 days prior to screening;
12. Participants who have consumed tea, coffee and/or other caffeine-containing beverages, grapefruit juice, or other beverages that affect liver enzyme activity (more than 8 cups, 1 cup = 250 mL) daily within 3 months prior to screening or are unable to abstain during the trial;
13. Participants with special dietary requirements or unable to follow a uniform diet (such as intolerance to standard meal foods, etc.); or participants who refuse to stop consuming pomelo/grapefruit or drinks made thereof, coffee, tea, or any food or beverage containing caffeine or rich in xanthine (such as animal offal, seafood, soy products, etc.) from 48 hours prior to dosing until the EOS;
14. Participants who drink alcohol or perform strenuous physical activities (including but not limited to strenuous weightlifting, running, and cycling) from 48 hours prior to dosing until the EOS;
15. Participants who are unable to complete the study due to their own reasons or are judged by the Investigator to be unsuitable for study participation for other reasons;

Part 2:

1. Participants who have required oral or intravenous antibiotics, anti-virals, anti-parasitics, anti-protozoals, or anti-fungals for the treatment of chronic or acute infection within 4 weeks prior to the screening visit;
2. Planned major surgical procedure during the length of the study;
3. Participants who are unable to complete the study due to their own reasons or are judged by the Investigator to be unsuitable for study participation for other reasons;