A Phase I/IIA, Randomized, Placebo-Controlled, Single-Ascending Dose (Part A, Participant- and Investigator-Blind) and Repeated-Dose (Part B, Participant-, Investigator-, and Sponsor-Blind) Study to Investigate the Safety, Pharmacokinetics, and Efficacy of UCB9741 in Healthy Study Participants (Part A) and in Study Participants With Moderate-to-Severe Atopic Dermatitis (Part B)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 107
- 试验地点
- 10
- 主要终点
- Incidents of treatment-emergent adverse events (TEAEs) during Part A
研究概览
简要总结
The purpose of the study is to investigate the safety and tolerability of single-ascending doses of UCB9741 administered by intravenous infusion or subcutaneous injection to healthy study participants and following repeat dosing at a single dose level in study participants with atopic dermatitis. Furthermore, the clinical efficacy outcome in study participants with atopic dermatitis after administration of UCB9741 by intravenous infusion will be investigated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- •Participant must be 18 to 55 years of age inclusive at the time of signing the informed consent form (ICF)
- •Participant must be overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring
- •Participant has a body mass index (BMI) within the range 18 to 30 kg/m^2 (inclusive)
- •Participant can be male or female
- •A male participant must agree to use contraception during the Treatment Period and for at least 90 days after the final dose of investigational medicinal product (IMP), and refrain from donating sperm during this period
- •A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
- •i) Not a woman of childbearing potential (WOCBP) OR ii) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 90 days after the final dose of IMP
- •Participant must be 18 to 65 years of age inclusive at the time of signing the ICF
- •Participant has a documented history of moderate or severe atopic dermatitis (AtD) that has been present for at least 12 months prior to initiating the study (signing of the ICF) and with:
- •validated Investigator Global Assessment (vIGA) score ≥3 at Screening (Visit 1) and Baseline (Visit 2)
- •Eczema Area and Severity Index (EASI) score of ≥14 at Screening (Visit 1) and ≥16 at Baseline (Visit 2)
- •Pruritus Numerical Rating Scale (NRS) score ≥ 3 at Screening (Visit 1) and Baseline (Visit 2)
- •≥10% body surface area (BSA) of AtD involvement at Screening (Visit 1) and Baseline (Visit 2)
- •Either documented recent history (within 6 months before the Screening Visit) of inadequate response to treatment with topical medications (regular use of topical corticosteroids [TCS] or topical calcineurin inhibitors [TCIs]) or when topical treatments are confirmed to be otherwise medically inadvisable (eg, because of important side effects or safety risks). Inadequate response is defined as failure to achieve and maintain remission or low disease remission or a low disease activity state (validated Investigator Global Assessment (vIGA) 0=clear to vIGA 2=mild) despite treatment with a daily regimen of TCS of medium to higher potency (±TCI as appropriate), applied for at least 4 weeks or for the maximum duration recommended by the product prescribing information (eg, 2 weeks for high potency TCS), whichever is shorter
- •Participant has a body mass index (BMI) within the range 18 to 32 kg/m^2 (inclusive)
- •Participant can be male or female
- •A male participant must agree to use contraception during the Treatment Period and for at least 60 days after the final dose of IMP, and refrain from donating sperm during this period
- •A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
- •i) Not a woman of childbearing potential (WOCBP) OR ii) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 60 days after the final dose of IMP
排除标准
- •Participant has a known hypersensitivity to any components of the investigational medicinal product (IMP) or other biologic drugs as stated in this protocol
- •Participant has a significant allergy to humanized monoclonal antibodies (mAbs)
- •Participant has clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe posttreatment hypersensitivity reactions
- •Participant has abnormal blood pressure (BP) (outside the normal range) in a supine position after 5 minutes rest
- •Participant has alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) >1.0x upper limit of normal (ULN)
- •Participant has a recent history or currently active clinically-significant bacterial, fungal, endoparasite, or viral (including hospitalization for coronavirus disease 2019 (COVID-19)) infection (within 6 months of the Screening Visit)
- •Participant has a history of inflammatory bowel disease (includes Crohn's disease and ulcerative colitis)
- •Participant has a history of diabetes
- •Participant has a corrected QT interval (QTc) >450 msec
- •Participant has received any prescription or nonprescription medicines, including over the counter remedies and herbal and dietary supplements (other than vitamins within recommended daily dose limits), within 14 days (or 5 half-lives of the respective drug, whichever is longer) prior to the Baseline Visit, other than contraceptives (oral, implants, or intrauterine devices) or occasional use of analgesics, such as paracetamol (acetaminophen, with or without caffeine, with a maximal dose of 4 g/day and 10 g/14 days)
- •Participant has received Bacillus Calmette-Guerin vaccinations within 1 year prior to the Baseline Visit or within 90 days after the final dose of IMP
- •Participant has been treated with biologic agents (such as mAbs, including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to the Baseline Visit
- •Participant has participated in another study of an IMP within the previous 90 days or 5 half-lives of the IMP (whichever longer), or is currently participating in another study of an IMP
- •Participant has sensitivity to heparin or heparin-induced thrombocytopenia
- •Participant has a known hypersensitivity to any components of the IMP or other biologic drugs as stated in this protocol
- •Participant has significant allergies to humanized mAbs
- •Participant has clinically significant multiple or severe drug allergies, or severe posttreatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear Immunoglobulin A (IgA) dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis)
- •Participant has abnormal BP (outside the normal range) in a supine position after 5 minutes rest
- •Participant has ALT, AST, or ALP >1.5xULN
- •Participant has a recent history of or clinically active clinically-significant, as judged by the Investigator, bacterial, fungal, endoparasite, or viral (or any history of hospitalization for COVID-19) infection (within 6 months of the Screening Visit)
- •Participant has a history of inflammatory bowel disease (includes Crohn's disease and ulcerative colitis)
- •Participant has a history of diabetes that is not well controlled with diet
- •Participant has a mean QT interval (QTc) >450 msec for male study participants or >470 msec for female study participants
- •Participant has received any prescription or nonprescription medicines, including over the counter remedies and herbal and dietary supplements (other than vitamins within recommended daily dose limits) within 14 days (or 5 half-lives of the respective drug, whichever is longer) prior to the Baseline Visit, other than contraceptives (oral, implants, or intrauterine devices) or occasional use of analgesics such as paracetamol (acetaminophen, with or without caffeine, with a maximal dose of 4 g/day and 10 g/14 days) or intranasal corticosteroids for seasonal rhinitis or inhaled bronchodilators and low dose inhaled corticosteroids for mild asthma
- •Participant has received Bacillus Calmette-Guerin vaccinations within 1 year prior to the Baseline Visit or is anticipated to do so within 60 days after the final dose of IMP
- •Participant has been treated with biologic agents (such as mAbs, including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to the Baseline Visit
- •Participant has participated in another study of an IMP within the previous 30 days or 5 half-lives of IMP (whichever longer) from the Baseline Visit or is currently participating in another study of an IMP
- •Participant has sensitivity to heparin or heparin-induced thrombocytopenia
研究组 & 干预措施
Part A: Intravenous UCB9741 arm 2
Subjects randomized to this arm will receive a pre-specified single intravenous dose of UCB9741.
干预措施: UCB9741 (Drug)
Part B: Intravenous Placebo arm
Subjects randomized to this arm will receive intravenous Placebo to maintain the blinding.
干预措施: Intravenous Placebo (Drug)
Part A: Intravenous Placebo arm
Subjects randomized to this arm will receive intravenous Placebo to maintain the blinding.
干预措施: Intravenous Placebo (Drug)
Part A: Subcutaneous Placebo arm
Subjects randomized to this arm will receive subcutaneous Placebo to maintain the blinding.
干预措施: Subcutaneous Placebo (Drug)
Part A: Intravenous UCB9741 arm 1
Subjects randomized to this arm will receive a pre-specified single intravenous dose of UCB9741.
干预措施: UCB9741 (Drug)
Part A: Intravenous UCB9741 arm 5
Subjects randomized to this arm will receive a pre-specified single intravenous dose of UCB9741.
干预措施: UCB9741 (Drug)
Part A: Intravenous UCB9741 arm 3
Subjects randomized to this arm will receive a pre-specified single intravenous dose of UCB9741.
干预措施: UCB9741 (Drug)
Part A: Intravenous UCB9741 arm 4
Subjects randomized to this arm will receive a pre-specified single intravenous dose of UCB9741.
干预措施: UCB9741 (Drug)
Part A: Subcutaneous UCB9741 arm 1
Subjects randomized to this arm will receive a pre-specified single subcutaneous dose of UCB9741.
干预措施: UCB9741 (Drug)
Part A: Subcutaneous UCB9741 arm 2
Subjects randomized to this arm will receive a pre-specified single subcutaneous dose of UCB9741.
干预措施: UCB9741 (Drug)
Part B: Intravenous UCB9741 arm
Subjects randomized to this arm will receive pre-specified intravenous doses of UCB9741.
干预措施: UCB9741 (Drug)
结局指标
主要结局
Incidents of treatment-emergent adverse events (TEAEs) during Part A
时间窗: From Baseline up to the End of Study Visit (Week 12)
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Incidents of treatment-emergent serious adverse events (TESAEs) during Part A
时间窗: From Baseline up to the End of Study Visit (Week 12)
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: * Results in death * Is life-threatening * Requires inpatient hospitalisation or prolongation of existing hospitalisation * Results in persistent or significant disability/incapacity, or * Is a congenital anomaly/birth defect * Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above
≥75% improvement vs Baseline in Eczema Area and Severity Index (EASI75) score during Part B
时间窗: Baseline, Week 12
The Eczema Area and Severity Index (EASI) is a validated scoring system that grades the physical signs of atopic dermatitis/eczema. A participant's EASI is scored through evaluation of 4 body regions: Head and neck; Trunk; Upper extremities; Lower extremities The severity of disease is evaluated by assessing each of 4 clinical signs for each area: Erythema; Edema/papulation; Excoriation; Lichenification The severity of each clinical sign is scored as: 0=None, 1=Mild, 2=Moderate, 3=Severe.
Incidents of TEAEs during Part B
时间窗: From Baseline up to the End of Study Visit (Week 18)
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Incidents of TESAEs during Part B
时间窗: From Baseline up to the End of Study Visit (Week 18)
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: * Results in death * Is life-threatening * Requires inpatient hospitalisation or prolongation of existing hospitalisation * Results in persistent or significant disability/incapacity, or * Is a congenital anomaly/birth defect * Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above
次要结局
- Cmax from Baseline through the End of Study (EoT) Visit of Part A(From Baseline through the End Of Study Visit (Week 12))
- AUC(0-t) from Baseline through the End of Study (EoT) Visit of Part A(From Baseline through the End of Study Visit (Week 12))
- Tmax from Baseline through the End of Study (EoT) Visit of Part A(From Baseline through the End of Study Visit (Week 12))
- ≥50% improvement vs Baseline in EASI score (EASI50) at Week 12 during Part B(Baseline, Week 12)
- ≥90% improvement vs Baseline in EASI score (EASI90) at Week 12 during Part B(Baseline, Week 12)
- AUCtau at Week 12 of Part B(Week 12)
- F% from Baseline through the End of Study (EoT) Visit of Part A(From Baseline through the End of Study Visit (Week 12))
- AUC from Baseline through the End of Study (EoT) Visit of Part A(From Baseline through the End of Study Visit (Week 12))
- Percent change from Baseline in the Eczema Area and Severity Index (EASI) score at Week 12 of Part B(Baseline, Week 12)
- Cmax after the final dose of Part B(Week 12)
- Tmax after the final dose of Part B(Week 12)