A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multi-Part, Single Ascending Dose and Multiple Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of ATTO-3712 in Healthy Adult Volunteers and Patients With Atopic Dermatitis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 48
- 试验地点
- 18
- 主要终点
- Incidence of AEs
研究概览
简要总结
The goal of this clinical trial is to assess the safety, tolerability, and pharmacokinetics of ATTO-3712 in healthy adults and patients with atopic dermatitis.
The main questions it aims to answer are:
What medical problems do participants have when taking ATTO-3712? How long does ATTO-3712 stay in the body after dosing? Researchers will compare ATTO-3712 to a placebo (a look-alike substance that contains no drug).
Participants will be dosed with ATTO-3712 or a placebo, visit the clinic for checkups and tests, and keep a diary of their symptoms.
详细描述
This is a 3-part study. Parts 1 and 2 will be a single and multiple ascending dose design, respectively, assessing the safety, tolerability, and PK of ATTO-3712 in healthy adult volunteers. Part 3 will consist of multiple doses in adult patients with atopic dermatitis to assess safety, tolerability, PK, and PD based on biomarkers in the blood.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- 是
入选标准
- •Parts 1&2 (Healthy Volunteers) Key Inclusion Criteria:
- •Any sex or gender who is 18 to 65 years old, inclusive, at Screening.
- •Body weight of 50 to 125 kg and body mass index (BMI) between 18.5 and 35 kg/m2
- •Considered in good general health based on medical history, physical exam, 12-lead ECG, screening clinical laboratory findings, and vital signs
- •Negative pregnancy test for participants of child-bearing potential.
- •Part 3 (Participants with Atopic Dermatitis) Key Inclusion Criteria:
- •Any sex or gender who is 18 to 65 years old
- •Body weight of 50 to 125 kg and BMI between 18.5 and 40 kg/m2
- •Clinically confirmed diagnosis of active AD
- •History of inadequate response to treatment with topical medications
- •Baseline weekly mean of daily PP-NRS ≥ 4 at Day
- •EASI score of ≥ 16 at Screening and Day 1
- •vIGA-AD score of ≥ 3 at Screening and Day 1
- •≥10% of body surface area (BSA) affected by AD at Screening and Day 1
- •Use of topical bland emollient (moisturizer) at least once daily for at least 5 of the 7 days immediately before Day 1 and agrees to continue using that same emollient at the same frequency throughout the study
- •Negative pregnancy test for participants of childbearing potential
- •Parts 1 & 2 (Healthy Volunteers) Key
排除标准
- •Any clinically significant underlying illness
- •History of malignancy within 5 years of Screening
- •History of major surgery within 8 weeks prior to Day 1 or has a major surgery planned during the study
- •History of uncontrolled asthma requiring rescue treatment with a bronchodilator for an increase in symptoms more than twice per week
- •History of hypersensitivity (including anaphylaxis) to a biologic medication, vaccine, an immunoglobulin product (plasma-derived or recombinant, eg, monoclonal antibody), or to any of the IP excipients (sucrose, polysorbate 80, or histidine)
- •Active hepatitis B virus (HBV) or hepatitis C virus (HCV) or is positive for HIV
- •Active or latent tuberculosis infection
- •Smoking more than 20 cigarettes (or cigars, cigarillos, or e-cigarettes equivalent) per day
- •History of drug or alcohol abuse
- •Laboratory values outside of the normal range
- •Part 3 (Participants with Atopic Dermatitis) Key Exclusion Criteria:
- •Any clinically significant underlying illness
- •Presence of skin comorbidities that may interfere with study assessments
- •Has taken prescription medication for the treatment of AD or other prohibited medication within the restricted time limits (defined in the protocol)
- •Has applied topical corticosteroids within 2 weeks prior to dosing.
- •History of malignancy within 5 years of Screening
- •History of major surgery within 8 weeks prior to Day 1 or has a major surgery planned during the study
- •History of uncontrolled asthma requiring rescue treatment with a bronchodilator for an increase in symptoms more than twice per week
- •History of recurrent eczema herpeticum
- •History of known primary immunodeficiency, is considered immunocompromised, history of untreated latent tuberculosis infection, has been treated for active tuberculosis in the past year, or has been treated for a parasitic infection in the past 6 months
- •History of major depression
- •History of hypersensitivity (including anaphylaxis) to a biologic medication, vaccine, an immunoglobulin product (plasma-derived or recombinant, eg, monoclonal antibody), or to any of the IP excipients (sucrose, polysorbate 80, or histidine)
- •Participant has experienced significant flare(s) in AD in the 2 weeks prior to Screening or during the Screening period
- •EASI score for the participant has more than doubled between Screening and Day 1
- •Active HBV or HCV or is positive for HIV
- •Participant is smoking more than 20 cigarettes (or cigars, cigarillos, or e-cigarettes equivalent to approximately 40 mg nicotine) per day
- •Participant has an ECG with a QTcF > 450 msec for males or > 470 msec for females at Screening
- •History of drug or alcohol abuse
- •Laboratory values outside of the normal range
研究组 & 干预措施
ATTO-3712 multiple dose SC
ATTO-3712 administered to dose level cohorts in multiple SC doses
干预措施: ATTO-3712 (Drug)
Placebo multiple dose SC
Placebo preparation to match Experimental Arm administered in multiple SC doses
干预措施: Placebo (Drug)
Placebo single dose IV
Placebo preparation to match Experimental Arm with single dose IV
干预措施: Placebo (Drug)
ATTO-3712 single dose SC
ATTO-3712 dose level cohorts receiving a single dose SC
干预措施: ATTO-3712 (Drug)
Placebo single dose SC
Placebo preparation to match Experimental Arm with single dose SC
干预措施: Placebo (Drug)
ATTO-3712 single dose IV
ATTO-3712 Dose level cohorts receiving a single dose IV
干预措施: ATTO-3712 (Drug)
结局指标
主要结局
Incidence of AEs
时间窗: 0-113 Days for SAD; 0-143 Days for MAD
The primary analysis will describe the incidence of AEs and laboratory abnormalities. AEs will be coded according to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA, version 28.0 or the current version). Their severity will be graded using the NCI CTCAE v5.0 or the current version.
Incidence of laboratory abnormalities
时间窗: 0-113 Days for SAD; 0-143 days for MAD
Clinical laboratory parameters (hematologic and blood chemistry) will be summarized by visit
Incidence of ECG abnormalities
时间窗: 0-113 Days for SAD; 0-143 Days for MAD
ECG findings (including QT abnormalities) will be summarized by visit.
Incidence of vital sign abnormalities
时间窗: 0-113 Days for SAD; 0-143 Days for MAD
Vital signs (systolic and diastolic blood pressure, temperature, heart rate) will be summarized by visit.
次要结局
- Incidence of Anti-Drug Antibodies(0-113 Days for SAD; 0-143 Days for MAD)
- Peak plasma concentration (Cmax) ATTO-3712(0-113 Days for SAD; 0-143 Days for MAD)
- Circulating half-life of ATTO-3712 (t1/2)(0-113 Days for SAD; 0-143 Days for MAD)
- Area Under the Plasma Concentration Versus Time Curve (AUC)(0-113 Days for SAD; 0-143 Days for MAD)
- Clearance Rate (C) of ATTO-3712(0-113 Days for SAD; 0-143 Days for MAD)
- Volume of Distribution (V) of ATTO-3712(0-113 Days for SAD; 0-143 Days for MAD)
- Bioavailability (F) of ATTO-3712(0-113 Days for SAD; 0-143 Days for MAD)