A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase Ⅰb Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Different Concentrations of ZYG24002 Lotion in Adult Patients With Mild to Moderate Seborrheic Dermatitis
概览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Supportive Safety Endpoints - The incidence rate of Adverse Events (AE) (including Grade 1-2)
概览
简要总结
This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase Ib clinical trial conducted in adult patients with mild to moderate seborrheic dermatitis (IGA-SD score of 2-3 points). The study aims to evaluate the safety, tolerability, and steady-state pharmacokinetic (PK) profiles of three concentrations (0.5%, 0.75%, and 1.0%) of ZYG24002 Lotion following continuous topical application once daily (QD) or twice daily (BID) for 28 days, and to conduct a preliminary exploration of the drug's efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 (inclusive) to 65 (inclusive) years, of either sex. Male subjects must have no childbearing potential or agree to adopt contraceptive measures until 3 months after the end of the study; female subjects of childbearing potential must be non-pregnant and non-lactating, and adopt reliable contraceptive measures during the study period and within 3 months after the last dose.
- •Diagnosed with seborrheic dermatitis by a dermatologist (diagnostic criteria refer to the Expert Consensus on Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Seborrheic Dermatitis (2024 Edition) and the 2015 Asian Consensus on Seborrheic Dermatitis), with a disease duration of ≥ 3 months; baseline Investigator's Global Assessment for Seborrheic Dermatitis (IGA-SD) score (0-4 point scale) of 2 (mild) or 3 (moderate); at baseline, the overall scores for erythema and scaling are at least mild severity (score 1) respectively. The involved body surface area (BSA%) is ≤ 10%, and skin lesions are distributed in at least two anatomical sites such as the scalp, face, and trunk.
- •No obvious signs of infection at the test site (e.g., pustules, crusts caused by bacterial infection). The subject is in good general skin condition at enrollment, with no other active skin lesions that may interfere with the clinical assessment.
- •Has not participated in any other clinical trials or used any investigational drugs within the past 3 months.
- •Study participants provide informed consent to participate in this study, sign the informed consent form (ICF), are able to understand the study requirements, and are willing to complete all scheduled visits and examinations in accordance with the investigator's instructions.
排除标准
- •Severe active seborrheic dermatitis: IGA-SD score of 4 points or extensive skin lesions (BSA \> 10%), accompanied by obvious exudation and infection, requiring systemic therapy. Participants whose disease activity is deemed unsuitable for study enrollment by the investigator (including but not limited to situations where 4 weeks of placebo-only treatment may lead to unacceptable disease progression).
- •Comorbidities of other skin diseases that may interfere with study assessments, such as psoriasis, severe acne, rosacea, atopic dermatitis, etc., which would confound the observation of seborrheic dermatitis lesions.
- •Administration of systemic glucocorticoids, systemic retinoids, immunosuppressants, oral/intravenous antifungals, phototherapy, PDE-4 inhibitors, or JAK inhibitors within 4 weeks; topical glucocorticoids, calcineurin inhibitors, PDE-4 inhibitors, antifungals, retinoids, keratolytics, selenium/tar-containing preparations on the study area within 2 weeks; any biologic agents within 6 months; or potent CYP3A4 inhibitors/inducers within 4 weeks.
- •Receipt of physical or chemical cosmetic treatments on the head and face within the past month (e.g., intense pulsed light, glycolic acid peels), resulting in temporary skin barrier dysfunction that has not yet recovered to normal.
- •A history of known severe hypersensitivity or severe adverse reactions to ZYG24002 or its excipients.
- •Comorbidities of other skin diseases that may increase the systemic absorption of ZYG24002, such as Netherton syndrome or erythroderma.
- •Current use of immunosuppressants or diagnosis of immune deficiency.
- •A history of malignancy within 5 years prior to screening or at screening.
- •Poorly controlled chronic diseases, including but not limited to endocrine disorders (e.g., diabetes mellitus with significantly elevated fasting blood glucose and obvious clinical symptoms, hyperthyroidism); a history of severe cardiovascular and cerebrovascular diseases (e.g., myocardial infarction, stroke); active peptic ulcers or chronic inflammatory bowel disease, etc.
- •Abnormal liver function: ALT or AST \> 2 × upper limit of normal (ULN), or total bilirubin \> 1.5 × ULN at screening; abnormal renal function: serum creatinine \> 1.5 × ULN; or other clinically significant abnormal laboratory findings that are deemed unsuitable for enrollment by the investigator.
研究组 & 干预措施
ZYG24002 0.5%， BID
Participants apply 0.5% concentration or placebo ZYG24002 Lotion twice daily (BID) for a consecutive period of 28 days.
干预措施: ZYG24002 0.5% (Drug)
ZYG24002 0.5%， BID
Participants apply 0.5% concentration or placebo ZYG24002 Lotion twice daily (BID) for a consecutive period of 28 days.
干预措施: ZYG24002 Placebo (Drug)
ZYG24002 0.75% ,BID
Participants apply 0.75% concentration or placebo ZYG24002 Lotion twice daily (BID) for a consecutive period of 28 days.
干预措施: ZYG24002 0.75% (Drug)
ZYG24002 0.75% ,BID
Participants apply 0.75% concentration or placebo ZYG24002 Lotion twice daily (BID) for a consecutive period of 28 days.
干预措施: ZYG24002 Placebo (Drug)
ZYG24002 1%, BID
Participants apply 1% concentration or placebo ZYG24002 Lotion twice daily (BID) for a consecutive period of 28 days.
干预措施: ZYG24002 1% (Drug)
ZYG24002 1%, BID
Participants apply 1% concentration or placebo ZYG24002 Lotion twice daily (BID) for a consecutive period of 28 days.
干预措施: ZYG24002 Placebo (Drug)
ZYG24002 1%, QD
Participants apply 1% concentration or placebo ZYG24002 Lotion once daily (QD) for a consecutive period of 28 days.
干预措施: ZYG24002 1% (Drug)
ZYG24002 1%, QD
Participants apply 1% concentration or placebo ZYG24002 Lotion once daily (QD) for a consecutive period of 28 days.
干预措施: ZYG24002 Placebo (Drug)
结局指标
主要结局
Supportive Safety Endpoints - The incidence rate of Adverse Events (AE) (including Grade 1-2)
时间窗: Through study completion, an average of 1 year
Record the types, incidence rates, severity, and drug-relatedness of all adverse events (AE) (including Grade 1-2) occurring during the treatment period (Day 1 - Day 35 ± 2)
The incidence rates of Serious Adverse Events (SAE) during the trial period
时间窗: Through study completion, an average of 1 year
Safety assessment will include the types and incidence rates of all serious adverse events (SAE) occurring during the study period; and the causal relationship between SAE and the study drug (assessed using a five-level evaluation method: Definite, Probable, Possible, Unlikely, Unrelated).
The incidence rate of adverse events (AE) occurring during the treatment period with severity grade ≥ 3
时间窗: Through study completion, an average of 1 year
Calculate the incidence rate of adverse events (AE) occurring during the treatment period with severity grade ≥ 3 (per CTCAE V5.0 criteria) ; record the specific types, severity, and causal relationship with the study drug of the aforementioned treatment-emergent adverse events (TEAE).
The incidence rate of adverse events (AE) occurring during the treatment period resulting in treatment discontinuation
时间窗: Through study completion, an average of 1 year
Calculate the incidence rate of adverse events (AE) occurring during the treatment period with resulting in treatment discontinuation; record the specific types, severity, and causal relationship with the study drug of the aforementioned treatment-emergent adverse events (TEAE).
Local Tolerability (LT) Indicator: the proportion of study participants with local cutaneous reactions of severity grade ≥ 2 during the study period
时间窗: Through study completion, an average of 1 year
Calculate the proportion of study participants with local cutaneous reactions (including stinging sensation, burning sensation, pruritus, erythema, and edema/papules) of severity grade ≥ 2 during the study period
Local Tolerability (LT) Indicator: the proportion of study participants with treatment interruption or discontinuation due to local tolerability adverse reactions
时间窗: Through study completion, an average of 1 year
Record the proportion of study participants with treatment interruption or discontinuation due to local tolerability adverse reactions, as well as the occurrence frequency, types, and trends of change of the aforementioned local tolerability reactions.
Supportive Safety Endpoints - the incidence rate of abnormalities in vital signs (blood pressure [BP], heart rate [HR], body temperature [BT])
时间窗: Through study completion, an average of 1 year
Calculate the incidence rate of abnormalities in vital signs (blood pressure \[BP\], heart rate \[HR\], body temperature \[BT\]); Record the changes in vital signs (blood pressure \[BP\], heart rate \[HR\], body temperature \[BT\]) and their clinical significance among study participants in each dose group during the treatment and follow-up periods
Supportive Safety Endpoints - The incidence rate of abnormalities in laboratory test indicators (including blood routine, blood biochemistry, urine routine)
时间窗: Through study completion, an average of 1 year
Calculate the incidence rate and severity of abnormalities in laboratory test indicators (including blood routine, blood biochemistry, urine routine) among study participants in each dose group during the treatment and follow-up periods
Supportive Safety Endpoints - The incidence rate of abnormalities in electrocardiogram (ECG) examinations
时间窗: Through study completion, an average of 1 year
Calculate the incidence rate of abnormalities in electrocardiogram (ECG) examinations and their clinical significance among study participants in each dose group during the treatment and follow-up periods
次要结局
- Time to peak concentration (Tmax)(Up to 24 hours after first dose)
- Single-dose exposure (Area Under the Curve from 0 to τ, AUC0-τ, τ=24 h for QD, τ=12 h for BID)(Up to 24 hours after first dose)
- Steady-state peak concentration (Cmax,ss)(Day 29)
- Steady-state trough concentration (Cmin,ss)(Day 29)
- Accumulation ratio (Rac): The ratio of steady-state Cmax,ss to single-dose Cmax(Day 29)
- Accumulation ratio (Rac): the ratio of steady-state AUC to single-dose AUC(Day 29)
- Change in Total Scaling Score on Day 29(Day 29)
- Change in Worst Itch Intensity (WI-NRS) on Day 15±1(Day 15)
- Change in Worst Itch Intensity (WI-NRS) on Day 29(Day 29)
- Change in DLQI Score(Day 29)
- Peak concentration (Cmax)(Up to 24 hours after first dose)
- IGA-SD Treatment Success Rate after treatment on Day 15±1(Day 15)
- IGA-SD Treatment Success Rate after treatment on Day 29(Day 29)
- Change in Total Erythema Score on Day 15±1(Day 15)
- Change in Total Erythema Score on Day 29(Day 29)
- Change in Total Scaling Score on Day 15±1(Day 15)