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)
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- UCB Biopharma SRL
- Enrollment
- 107
- Locations
- 10
- Primary Endpoint
- Incidents of treatment-emergent adverse events (TEAEs) during Part A
Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •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)
Exclusion Criteria
- •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)
Arms & Interventions
Part A: Intravenous UCB9741 arm 2
Subjects randomized to this arm will receive a pre-specified single intravenous dose of UCB9741.
Intervention: UCB9741 (Drug)
Part B: Intravenous Placebo arm
Subjects randomized to this arm will receive intravenous Placebo to maintain the blinding.
Intervention: Intravenous Placebo (Drug)
Part A: Intravenous Placebo arm
Subjects randomized to this arm will receive intravenous Placebo to maintain the blinding.
Intervention: Intravenous Placebo (Drug)
Part A: Subcutaneous Placebo arm
Subjects randomized to this arm will receive subcutaneous Placebo to maintain the blinding.
Intervention: Subcutaneous Placebo (Drug)
Part A: Intravenous UCB9741 arm 1
Subjects randomized to this arm will receive a pre-specified single intravenous dose of UCB9741.
Intervention: UCB9741 (Drug)
Part A: Intravenous UCB9741 arm 5
Subjects randomized to this arm will receive a pre-specified single intravenous dose of UCB9741.
Intervention: UCB9741 (Drug)
Part A: Intravenous UCB9741 arm 3
Subjects randomized to this arm will receive a pre-specified single intravenous dose of UCB9741.
Intervention: UCB9741 (Drug)
Part A: Intravenous UCB9741 arm 4
Subjects randomized to this arm will receive a pre-specified single intravenous dose of UCB9741.
Intervention: UCB9741 (Drug)
Part A: Subcutaneous UCB9741 arm 1
Subjects randomized to this arm will receive a pre-specified single subcutaneous dose of UCB9741.
Intervention: UCB9741 (Drug)
Part A: Subcutaneous UCB9741 arm 2
Subjects randomized to this arm will receive a pre-specified single subcutaneous dose of UCB9741.
Intervention: UCB9741 (Drug)
Part B: Intravenous UCB9741 arm
Subjects randomized to this arm will receive pre-specified intravenous doses of UCB9741.
Intervention: UCB9741 (Drug)
Outcomes
Primary Outcomes
Incidents of treatment-emergent adverse events (TEAEs) during Part A
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Secondary Outcomes
- 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)