A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of UCB8600 in Healthy Participants, Atopic Participants, and Chronic Spontaneous Urticaria Participants

Sponsor

UCB Biopharma SRL (Industry)

Overall Status

Terminated

CT.gov ID

NCT04444466

Collaborator

(none)

Enrollment

Location

Arms

13.1

Actual Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to assess safety, tolerability and pharmacokinetics (PK) of oral UCB8600.

Condition or Disease	Intervention/Treatment	Phase
Healthy Study Participants Chronic Spontaneous Urticaria	Drug: UCB8600 Other: Placebo	Phase 1

Detailed Description

The Study was only open for recruitment of Healthy Study Participants (Part A) prior to termination and did not enroll any patient population.

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Cohort designCohort design

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

This is an investigator- and participant-blind study.

Primary Purpose:

Basic Science

Official Title:

A First-In-Human, Randomized, Participant-Blind, Investigator-Blind, Placebo-Controlled, Single- and Multiple-Dose, Dose-Escalating Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of UCB8600 in Healthy Participants, Atopic Participants, and Chronic Spontaneous Urticaria Participants

Actual Study Start Date :

Jun 30, 2020

Actual Primary Completion Date :

Aug 2, 2021

Actual Study Completion Date :

Aug 2, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: UCB8600 Study participants randomized to this arm will receive various single doses and multiple doses of UCB8600 administered to various cohorts.	Drug: UCB8600 Study participants will receive UCB8600 in a pre-specified sequence during the Treatment Period.
Placebo Comparator: Placebo Study participants randomized to this arm will receive various single doses and multiple doses of Placebo administered to various cohorts.	Other: Placebo Study participants will receive Placebo in a pre-specified sequence during the Treatment Period matching UCB8600. Other Names: PBO

Arm

Intervention/Treatment

Experimental: UCB8600

Study participants randomized to this arm will receive various single doses and multiple doses of UCB8600 administered to various cohorts.

Drug: UCB8600

Study participants will receive UCB8600 in a pre-specified sequence during the Treatment Period.

Placebo Comparator: Placebo

Study participants randomized to this arm will receive various single doses and multiple doses of Placebo administered to various cohorts.

Other: Placebo

Study participants will receive Placebo in a pre-specified sequence during the Treatment Period matching UCB8600.

Other Names:

PBO

Outcome Measures

Primary Outcome Measures

Incidence of treatment-emergent adverse events (TEAEs) [From Baseline (Day 1) until the End of Study (up to Day 42)]
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A treatment-emergent adverse event is characterized according to the intake of the study medication.

Secondary Outcome Measures

The maximum plasma concentration (Cmax) of a single dose UCB8600 [Plasma samples will be taken predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 216 hours postdose]
Cmax: Maximum observed plasma concentration
Time to maximum plasma concentration (tmax) of a single dose UCB8600 [Plasma samples will be taken predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 216 hours postdose]
tmax: Time to maximum observed plasma concentration
The area under the curve (AUC) of a single dose UCB8600 [Plasma samples will be taken predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 216 hours postdose]
AUC0-infinity: Area under the plasma concentration time curve from time 0 to infinity
The maximum plasma concentration (Cmax) of multiple doses UCB8600 [Plasma samples will be taken on Day 1, 9 and 14 at: predose, 0.5, 1, 2, 3, 6, 12, 24 hours postdose]
Cmax: Maximum observed plasma concentration
Time to maximum plasma concentration (tmax) of multiple doses UCB8600 [Plasma samples will be taken on Day 1, 9 and 14 at: predose, 0.5, 1, 2, 3, 6, 12, 24 hours postdose]
tmax: Time to maximum observed plasma concentration
The area under the curve (AUCtau) over a dosing interval on Day 1 of multiple doses UCB8600 [Plasma samples will be taken on Day 1 at: predose, 0.5, 1, 2, 3, 6, 12, 24 hours postdose]
AUCtau: Area Under the Curve over a dosing interval
The area under the curve (AUCtau) over a dosing interval on Day 9 of multiple doses UCB8600 [Plasma samples will be taken on Day 9 at: predose, 0.5, 1, 2, 3, 6, 12, 24 hours postdose]
AUCtau: Area Under the Curve over a dosing interval
The area under the curve (AUCtau) over a dosing interval on Day 14 of multiple doses UCB8600 [Plasma samples will be taken on Day 14 at: predose, 0.5, 1, 2, 3, 6, 12, 24 hours postdose]
AUCtau: Area Under the Curve over a dosing interval

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Applicable to Parts A-D

Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent
Participants who are overtly healthy (in the opinion of the investigator) as determined by medical evaluation including medical history (any chronic and acute illness), physical examination, vital signs, 12-lead electrocardiogram (ECG), and laboratory screening tests at the Screening Visit
Body weight 45 kg or greater and body mass index (BMI) within the range 19 and 30 kg/m^2 (inclusive)

Part B-specific

Study participants must have a Screening serum immunoglobulin E (IgE) of ≥30 kU/L and ≤700 kU/L for inclusion in Cohort 1 through Cohort 4a and >700 kU/L for inclusion in Cohort 4b
Study participants must be documented to be sensitized to at least 1 common aeroallergen confirmed by (skin prick test (SPT) at Screening)

Part C-specific

Study participants must have a diagnosis of chronic spontaneous urticaria (CSU) diagnosed by a dermatologist, allergist or clinical immunologist and have persistent symptoms most days of the week for the last 6 weeks despite regular use of an H1 antihistamine according to the EAACI/GA²LEN/EDF/WAO guideline
Study participants must have a documented 7-day Urticaria Assessment Score (UAS7) score of 16 or above and an 7-day Itch Severity Score (ISS7) of 8 or above at Visit 2 (Day -1, Admission)
Study participants must have a Screening serum immunoglobulin E (IgE) of ≥30 kU/L

Exclusion Criteria:

Applicable to Parts A-D

Participant has any (acute or chronic [including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection]) medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the study participant's ability to participate in this study
Study participant has 12-lead electrocardiogram (ECG) with changes considered to be clinically significant (eg, QT interval corrected using Fridericia's formula (QTcF)

450 msec , left bundle branch block, or evidence of myocardial ischemia) at the Screening Visit or Day -1 (Admission)

A history of additional risk factors for Torsades de pointes (TdP) (eg, heart failure, hypokalemia, family history of Long QT Syndrome)
Study participant has a history of atopy, allergic rhinitis, urticaria, angioedema, asthma, food allergies, or anaphylaxis
Study participant has a known hypersensitivity to any components of the study medication or comparative drugs as stated in this protocol
Study participant has a history of drug allergy or other allergy that, in the opinion of the investigator or UCB Study Physician, contraindicates his/her participation
Study participants with evidence of helminthic parasitic infection as evidenced by stools being positive for a pathogenic organism according to local guidelines. All participants will be screened at Screening. If stool testing is positive for pathogenic organism, the participants will not enter Treatment Period and will not be allowed to rescreen
Study participant has received prescription or nonprescription medicines (including over-the-counter medicines and herbal and dietary supplements [including St John's Wort]) that have been taken within 14 days prior to Screening. Drugs that are strong or moderate inhibitors or inducers of cytochrome P450 (CYP)3A4 and/or P-glycoprotein (Pgp) are prohibited
The use of concomitant medications that prolong the QT/QTc interval
Study participant has donated more than 500 mL of blood or blood products within 90 days prior to Admission (Day -1) or plans to donate blood during the study (20 weeks post Screening)
Study participant has consumed any grapefruit, grapefruit juice, grapefruit-containing products, or star fruit within 14 days prior to administration of UCB8600

Part B-specific

Study participant has:

a history of angioedema, severe asthma, severe food allergies, or anaphylaxis
a personal or family history of cardiomyopathy

A Screening forced expiratory volume (FEV1) <80% predicted (highest of 3)
Study participant has:

Allergen immunotherapy, also known as desensitization or hyposensitization at a maintenance licensed dose (depending on the type of immunotherapy [subcutaneous or sublingual]) for ≥3 months prior to Screening and then throughout the study
Severe positive reaction to Screening skin prick test

Topical or systemic corticosteroids, including high dose oral (>5 mg prednisolone), in the past 14 days prior to Screening and throughout the study
Topical immunosuppressants in the past 14 days prior to Screening and throughout the study
Tricyclic antidepressants, prescription antihistamines, over-the-counter antihistamines, and heartburn medications in the past 14 days prior to Admission
Systemic immunosuppressants such as azathioprine, methotrexate, cyclosporine, and mycophenolate mofetil in the past 4 weeks prior to Screening and throughout the study
Biologics such as omalizumab for the past 6 months prior to Screening and throughout the study

Part C-specific

Study participant has:

a history of angioedema, severe asthma, severe food allergies, or anaphylaxis
a personal or family history of cardiomyopathy

Study participants with a serum IgE level of >1000 kU/L
A screening FEV1 <80% predicted (average of 3)
Allergen immunotherapy, also known as desensitization or hyposensitization at a maintenance licensed dose (depending on the type of immunotherapy [subcutaneous or sublingual]) for ≥3 months prior to Screening and then throughout the study
Topical or systemic corticosteroids, including high dose oral (>5 mg prednisolone), in the past 14 days prior to Screening and throughout the study
Topical immunosuppressants in the past 14 days prior to Screening and throughout the study
Systemic immunosuppressants such as azathioprine, methotrexate, cyclosporine, and mycophenolate mofetil in the past 4 weeks prior to Screening and throughout the study
Biologics such as omalizumab for the past 6 months prior to Screening and throughout the study