Clinical trial NCT05843422: A First-in-Human Study of QY211 Gel in Adult Subjects
Official title: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Efficacy of Single and Multiple Topical Doses of QY211 Gel in Healthy Chinese Subjects and Patients With Mild to Moderate Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Atopic Dermatitis
Lead sponsor: E-nitiate Biopharmaceuticals (Hangzhou) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-05-06
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase Ia/Ib,Randomized, Double-Blind, Placebo-Controlled Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Efficacy of Single and Multiple Topical Doses of QY211 Gel in Healthy Chinese Subjects and Patients with Mild to Moderate Atopic Dermatitis


Eligibility criteria: Inclusion Criteria:

Part 1

1. Male or female subjects (male or female) aged 18-45 years (inclusive);
2. Body weight ≥ 50.0 kg for males and ≥ 45.0 kg for females; body mass index (BMI) within the range of 18.0 to 27.0 kg/m2 (including the cut-off value);
3. the investigator determined vital signs, physical examination, clinical laboratory test values (blood routine, urine routine, blood biochemistry, coagulation function, pregnancy test (female), hepatitis, HIV, syphilis), routine 12-lead ECG results in line with healthy subjects
4. the subject fully understood the purpose, nature, methods and possible adverse reactions of the trial, volunteered to participate, and signed informed consent before the start of any study procedures;
5. the subject was able to communicate well with the investigator, and understand and comply with the requirements of this study.

Part 2

1. Male and female patients aged 18-65 years (including the boundary value);
2. Meet Hanifin-Rajka diagnostic criteria at screening and have a history of AD for at least 6 months ;
3. IGA score of 2 (mild) or 3 (moderate) at screening and baseline;
4. The total area of atopic dermatitis lesions is 5% -20% BSA
5. Patients fully understand the purpose, nature, methods and possible adverse reactions of the trial, voluntarily participate, and sign an informed consent form before the start of any study procedures;
6. Patients can communicate well with the investigator and comply with the study and follow-up procedures;

Exclusion Criteria:

Part 1

1. Allergic constitution, such as allergic to two or more drugs and food; or known to be allergic to the composition of this drug (QY201 and excipients: carbomer (homopolymer type B 974P NF), edetate disodium, sodium hydroxide, propylene glycol and purified water);
2. Patients who have received surgery within 3 months before screening, or plan to undergo surgery during the study period, or have received surgery that will affect drug absorption, distribution, metabolism and excretion;
3. Previous or current cardiovascular, liver, kidney, respiratory, blood and lymphatic, endocrine, immune, mental, neurological, gastrointestinal system, metabolism and bone diseases, and the investigators believe that the subjects have clinical significance, not suitable for the trial;
4. Patients who can not tolerate venipuncture, have a history of fainting needle, halo blood;
5. History or presence of clinically relevant skin diseases that, in the opinion of the investigator, contraindicate the study or affect the assessment of the site of administration, including psoriasis, eczema, acne, atopic dermatitis, dysplastic mole, other skin lesions, history of skin cancer, or skin diseases that affect the safety evaluation of the test drug;
6. Vaccination with live (attenuated) vaccines within 2 months prior to screening;
7. Smoking or drinking within 3 months before screening (smoking: \> 10 cigarettes/day; drinking: \> 15 g pure alcohol/day, equivalent to 450 mL beer, 150 mL wine or 50 mL low-grade liquor), or alcohol and drug abuse (morphine/methylamphetamine/ketamine/methylenedioxyamphetamine/tetrahydrocannabinolic acid/cocaine) test positive;
8. Participated in other drug or device clinical trials within 3 months before screening;
9. Non-physiological blood loss ≥ 400 mL (including trauma, blood collection, blood donation) within 3 months before screening, or plan to donate blood during the study or within 1 month after the end of the study;
10. Pregnant women, lactating women, or subjects who have plans to donate sperm or eggs, or (including male and female subjects) refuse to voluntarily take effective contraceptive measures from the screening period to 6 months after the end of the last dose;
11. Use of any other drugs, including oral or topical drugs such as prescription drugs, over-the-counter drugs, and herbal medicines, except vitamins and/or paracetamol, within 2 weeks before screening;
12. Drinking excessive tea, coffee and/or caffeine-rich beverages (more than 8 cups, 1 cup = 250 mL) every day within 3 months before screening;
13. Subjects have skin conditions in the target application area (back, lateral arm area) that affect the tolerability assessment of the study, such as tattoos;
14. Subjects who are judged unsuitable for participation by other investigators;

Part 2

1. Patients with or suspected active tuberculosis, latent untreated tuberculosis, incompletely cured tuberculosis or Mycobacterium tuberculosis infection (except for treatment records that prove that patients have been adequately treated, according to the medical judgment of the investigator and/or infectious disease experts, can enter this study) as judged by the investigator and/or infectious disease specialist (combined with medical history, symptoms, signs, laboratory tests, T-spot test, imaging examination);
2. Hepatitis B surface antigen (HBsAg) positive or hepatitis C virus antibody (HCV-Ab) positive during screening; or HIV antibody or Treponema pallidum antibody positive;
3. Patients with any clinical symptoms of bacterial, viral, parasitic or fungal infection requiring treatment during the screening period;
4. Previous disseminated herpes zoster (single attack), or disseminated herpes simplex (single attack), or recurrent (≥ 2 attacks) local herpes zoster;
5. Patients with a history of mental illness or genetic history of mental illness or epilepsy, the use of antipsychotic drugs, sedative drugs;
6. In addition to a history of atopic dermatitis, previous history of other connective tissue diseases, or severe cardiovascular, liver, kidney, digestive tract, nerve, skin and other diseases, or patients with malignant tumors (except completely removed cervical carcinoma in situ or non-metastatic cutaneous squamous cell carcinoma or basal cell carcinoma), systemic sex hormone therapy or other interventions may be required, and participation in this study may be at risk as judged by the investigator;
7. Patients with non-immune factors (such as hyperlipidemia, diabetes, thyroid disease, severe heart abnormalities, etc.);
8. Patients who have previously suffered from lymphatic diseases, or have signs or symptoms of lymphoproliferative diseases, including but not limited to lymph nodes or splenomegaly;
9. In addition to atopic dermatitis, suffering from other skin diseases that affect the evaluation of the test results, or the presence of large tattoos, birthmarks, skin scars and other conditions in the skin lesions;
10. Known immunodeficiency disease or first-degree relatives with hereditary immunodeficiency disease;
11. Patients with cerebral hemorrhage or cerebral infarction within 1 year;
12. Patients with previous thromboembolism (including deep venous thrombosis, pulmonary embolism, arterial thrombosis, etc.) or other high-risk groups prone to thromboembolism;
13. Previous or planned organ transplantation (such as liver and kidney transplantation);
14. Clinical or laboratory tests judged by the investigator as abnormal with clinical significance;
15. History of alcoholism or drug abuse within 6 months before screening;
16. Participated in any investigational drug 4 weeks (or 5 half-lives, whichever is longer) before screening or participated in any medical device clinical trial within 3 months;
17. Non-physiological blood loss ≥ 400 mL (including trauma, blood sampling, blood donation) within 3 months before screening, or plan to donate blood during the study or within 1 month after the end of the study;
18. Patients with the following cardiac abnormalities:

    1. Acute myocardial infarction, unstable angina pectoris, coronary artery bypass grafting or coronary stent implantation within 3 months prior to screening;
    2. Severe arrhythmia (e.g., second-degree type 2 or third-degree atrioventricular block, long QT syndrome or QTcF abnormalities: male \> 470 ms female \> 480 ms, atrial fibrillation, frequent premature beats);
    3. Decompensated cardiac insufficiency (NYHA class III or IV);
    4. Other cardiac diseases requiring treatment and assessed by the investigator as inappropriate for participation in this study;
19. Systemic or local use of JAK inhibitors (eg, Ruxolitinib, Tofacitinib, Baricitinib, Filgotinib, Lestaurtinib, Pacritinib, Delgocitinib, Upadacitinib, Abrocitinib, etc) within 3 months prior to screening;
20. Major surgical procedures or serious trauma within 8 weeks prior to screening or anticipation of major surgical procedures during the trial (defined as major surgical procedures referring to Grade 3 and 4 procedures as specified in the Measures for the Management of Clinical Applications of Medical Technology implemented on November 1, 2018), and all surgical or major trauma-related AEs had not recovered (recovered to CTCAEv5.0 ≤ Grade 1 or baseline) before screening.
21. Received biological therapy for atopic dermatitis (including but not limited to dupilumab) within 8 weeks (or 5 elimination half-lives, whichever is longer) before randomization;
22. Received live (attenuated) vaccine within 4 weeks before randomization, or planned to receive live (attenuated) vaccine during treatment and within 4 weeks after the last use of investigational product;
23. Patients who have used long-acting anticoagulants (such as warfarin, dabigatran, etc.) or need to continue anticoagulant therapy (except aspirin ≤ 100 mg/day) within 4 weeks before randomization;
24. Receiving systemic therapy (including glucocorticoids, cyclosporine, mycophenolate mofetil, interferon γ, azathioprine, methotrexate, tripterygium wilfordii tablets and other Chinese herbal medicines) known or likely to affect atopic dermatitis within 4 weeks (or 5 half-lives, whichever is longer) before randomization, phototherapy (such as UVB, PUVA, etc.) or receiving antihistamines within 2 weeks before randomization;
25. Patients who have received topical drugs known or likely to affect atopic dermatitis within 2 weeks before randomization, including but not limited to topical glucocorticoids (TCS), calcineurin inhibitors (TCI), topical phosphodiesterase 4 (PDE 4) inhibitors;
26. Use of topical antibiotics, antibacterial soap, sodium hypochlorite in the target application area within 7 days before randomization, or use of emollients not provided by the sponsor or designated by the investigator within 12 hours before baseline;
27. Allergic constitution or suspected allergy to the active ingredients or excipients of the investigational drug;
28. Pregnant women, lactating women, or patients (including male and female patients) refuse to voluntarily take effective contraceptive measures during the screening period until 6 months after the end of the last dose (see Appendix 2 for details);
29. Do not avoid prolonged exposure to natural or artificial ultraviolet (UV) radiation, or plan to perform such exposure during the study, and the investigator believes that it may affect atopic dermatitis;
30. Any patient considered unsuitable for participation in this clinical study by the investigator.

Primary outcomes:
measure: Part1:Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 to Day 13
measure: Part1:Number of Participants With Clinical Laboratory Abnormalities
timeFrame: Day 3 to Day 13
measure: Part1:Number of Participants With Clinically Significant Changes Form Baseline in Physical Examination
timeFrame: Day 3 to Day 13
measure: Part1:Number of Participants With Clinically Significant Treatment-emergent Electrocardiogram (ECG) Findings
timeFrame: Day 3 to Day 13
measure: Part 1:Number of Participants With Clinically Significant Changes Form Baseline in Vital Signs
timeFrame: Day 1 to Day 13
measure: Part 1:Severity of local skin irritation
timeFrame: Day 1 to Day 13
measure: Part 2:Number of Participants With Adverse Events (AEs) and Serious Adverse Events
timeFrame: Day 1 to Day 31
measure: Part2:Number of Participants With Clinical Laboratory Abnormalities
timeFrame: Day 8 to Day 29
measure: Part2:Number of Participants With Clinically Significant Changes Form Baseline in Physical Examination
timeFrame: Day 8 to Day 29
measure: Part2:Number of Participants With Clinically Significant Treatment-emergent Electrocardiogram (ECG) Findings
timeFrame: Day 8 to Day 29.
measure: Part 2:Number of Participants With Clinically Significant Changes Form Baseline in Vital Signs
timeFrame: Day 8 to Day 30
Secondary outcomes:
measure: Rate of change from baseline in Eczema Area and Severity Index (EASI) in patients（part 2 only）
timeFrame: Up to 4 weeks
measure: Proportion of patients with at least a 2-point improvement in IGA score from baseline（part 2 only）
timeFrame: Up to 4 weeks
measure: Percentage of Participants Achieving >=50%/75%/90% Improvement From Baseline in Eczema Area and Severity Index (EASI-50/EASI-75/EASI-90) Response（part2 only）
timeFrame: Up to 4 weeks
measure: Change from baseline in Peak daily Pruritus NRS score (PP-NRS) （part 2 only）
timeFrame: Up to 29 days
measure: Rate of change from baseline in SCORAD score （part 2 only）
timeFrame: Up to 4 weeks
measure: Change from baseline in total score of Dermal Quality of Life Index Questionnaire (DLQI) （part 2 only）
timeFrame: Up to 4 weeks
measure: Rate of change from baseline in atopic dermatitis in BSA（part 2 only）
timeFrame: Up to 4 weeks
measure: Tmax of QY211-Single and Multiple Dose Drugs
timeFrame: Up to 29 days
measure: Cmax of QY211-Single and Multiple Dose Drugs
timeFrame: Up to 29 days
measure: t1/2 of QY211-Single and Multiple Dose Drugs
timeFrame: Up to 29 days
measure: AUC QY211-Single and Multiple Dose Drugs
timeFrame: Up to 29 days
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan Hospital Affiliated to Fudan University
state: Shanghai
Study officials:
References: