A Phase 1/2A, Randomized, Placebo-Controlled, Single-Ascending Dose (Part A, Participant- and Investigator-Blind) and Repeat-Dose (Part B, Participant-, Investigator-, and Sponsor-Blind) Study to Investigate the Safety, Pharmacokinetics, and Efficacy (Part B Only) of UCB1381 in Healthy Study Participants (Part A) and in Study Participants With Moderate to Severe Atopic Dermatitis (Part B)
Overview
- Phase
- Phase 1
- Intervention
- UCB1381
- Conditions
- Atopic Dermatitis
- Sponsor
- UCB Biopharma SRL
- Enrollment
- 273
- Locations
- 16
- Primary Endpoint
- Incidents of treatment-emergent adverse events (TEAEs) from Baseline through the End of Study (EOS) Visit (Week 12) in Part A
- Status
- Completed
- Last Updated
- 6 months ago
Overview
Brief Summary
The purpose of the study is to investigate the safety and tolerability of single-ascending doses of UCB1381 (intravenous and subcutaneous) in healthy study participants and after repeat intravenous dosing in study participants with atopic dermatitis. Efficacy will be assessed following repeat intravenous dosing versus placebo in study participants with atopic dermatitis.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Part A Healthy study participants
- •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/m2 (inclusive)
- •Participant can be male or female and must agree to use contraception
- •Part B Participants with moderate to severe Atopic dermatitis (AtD)
- •Participant must be 18 to 65 years of age inclusive at the time of signing the ICF
- •Participant has moderate or severe AtD that has been present for at least 12 months prior to initiating the study (signing of the ICF) and with:
- •A validated Investigator Global Assessment (vIGA) score ≥3 at Screening and Baseline
- •An Eczema Area and Severity Index (EASI) score of ≥14 at Screening and ≥16 at Baseline
Exclusion Criteria
- •Part A Healthy study participants
- •Participant has a history or presence of any medical or psychiatric condition, physical examination finding, laboratory test result, electrocardiogram (ECG), or vital sign that, in the opinion of the investigator, could significantly alter the absorption, metabolism, or elimination of drugs; constitute a risk when taking the study intervention; or interfere with the interpretation of data
- •Participant has a known hypersensitivity to any components of the investigational medicinal product (IMP) or other biologic drugs (including humanized monoclonal antibodies (mAbs)), clinically significant drug allergies, or history of severe adverse reactions after drug administration
- •Participant has a past history of inflammatory bowel disease (includes Crohn's disease and ulcerative colitis)
- •Participant has previously been randomized in this study
- •Participant has participated in another study of an IMP or has received any biologic agent (such as mAbs, including marketed drugs and including biologic agents that target interleukin (IL)-13 or IL-22) within the 30 days prior to Screening or 5 half-lives (whichever is longer), if this information can be validated by the investigator
- •Part B Participants with moderate to severe AtD
- •Participant has a history or presence of any medical or psychiatric condition, physical examination finding, laboratory test result, electrocardiogram (ECG), or vital sign that, in the opinion of the investigator, could significantly alter the absorption, metabolism, or elimination of drugs; constitute a risk when taking the study intervention; or interfere with the interpretation of data
- •Participant has a known hypersensitivity to any components of the IMP or other biologic drugs (including humanized mAbs), clinically significant drug allergies, or history of severe adverse reactions after drug administration
- •Participant has a past history of inflammatory bowel disease (includes Crohn's disease and ulcerative colitis)
Arms & Interventions
UCB1381 dosing regime 1 in Part A
Participants will be randomized to receive a single dose UCB1381 intravenously (iv).
Intervention: UCB1381
UCB1381 dosing regime 5 in Part A
Participants will be randomized to receive a single dose UCB1381 subcutaneously (sc).
Intervention: UCB1381
UCB1381 dosing regime 2 in Part A
Participants will be randomized to receive a single dose UCB1381 intravenously (iv).
Intervention: UCB1381
UCB1381 dosing regime 3 in Part A
Participants will be randomized to receive a single dose UCB1381 intravenously (iv).
Intervention: UCB1381
UCB1381 dosing regime 4 in Part A
Participants will be randomized to receive a single dose UCB1381 intravenously (iv).
Intervention: UCB1381
UCB1381 dosing regime 6 in Part A
Participants will be randomized to receive a single dose UCB1381 subcutaneously (sc).
Intervention: UCB1381
UCB1381 dosing regime 7 in Part A
Participants will be randomized to receive a single dose UCB1381 intravenously (iv).
Intervention: UCB1381
UCB1381 dosing regime 8 in Part A
Participants will be randomized to receive a single dose UCB1381 intravenously (iv).
Intervention: UCB1381
UCB1381 dosing regime 9 in Part B
Participants will be randomized to receive repeated doses UCB1381 intravenously (iv).
Intervention: UCB1381
Placebo iv Arm Part A
Participants will be randomized to receive a single dose of placebo iv to maintain the blinding.
Intervention: Placebo
Placebo sc Arm Part A
Participants will be randomized to receive a single dose of placebo sc to maintain the blinding.
Intervention: Placebo
Placebo iv Arm Part B
Participants will be randomized to receive repeated doses of placebo iv to maintain the blinding.
Intervention: Placebo
Outcomes
Primary Outcomes
Incidents of treatment-emergent adverse events (TEAEs) from Baseline through the End of Study (EOS) Visit (Week 12) in Part A
Time Frame: From Baseline up to Week 12 in Part A
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study medication.
Incidents of treatment-emergent serious adverse events (TESAEs) from Baseline through the EOS Visit (Week 12) in Part A
Time Frame: From Baseline up to Week 12 in Part A
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
Incidents of TEAEs from Baseline through the EOS Visit (Week 22) in Part B
Time Frame: From Baseline up to Week 22 in Part B
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study medication.
≥75% improvement vs Baseline (Yes/No) in Eczema Area and Severity Index score (EASI75) at Week 12 in Part B
Time Frame: From Baseline up to Week 12 in Part B
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 TESAEs from Baseline through the EOS Visit (Week 22) in Part B
Time Frame: From Baseline up to Week 22 in Part B
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
- UCB1381 Cmax from Baseline through the EOS Visit (Week 12) in Part A(From Baseline up to Week 12 in Part A)
- UCB1381 Tmax from Baseline through the EOS Visit (Week 12) in Part A(From Baseline up to Week 12 in Part A)
- UCB1381 AUC(0-t) from Baseline through the EOS Visit (Week 12) in Part A(From Baseline up to Week 12 in Part A)
- UCB1381 F% from Baseline through the EOS Visit (Week 12) in Part A(From Baseline up to Week 12 in Part A)
- Percent change from Baseline in EASI score at Week 12 in Part B(From Baseline up to Week 12 in Part B)
- ≥50% improvements vs Baseline (Yes/No) in EASI score (EASI50) at Week 12 in Part B(From Baseline up to Week 12 in Part B)
- UCB1381 Tmax at week 12 after the final dose in Part B(From Baseline up to Week 12 in Part B)
- UCB1381 AUCtau at week 12 after the final dose in Part B(From Baseline up to Week 12 in Part B)
- UCB1381 AUC from Baseline through the EOS Visit (Week 12) in Part A(From Baseline up to Week 12 in Part A)
- ≥90% improvements vs Baseline (Y/N) in EASI score (EASI90) at Week 12 in Part B(From Baseline up to Week 12 in Part B)
- Validated Investigator Global Assessment (vIGA) score of 0 or 1 (Y/N) at Week 12 in Part B(From Baseline up to Week 12 in Part B)
- UCB1381 Cmax at week 12 after the final dose in Part B(From Baseline up to Week 12 in Part B)