Safety and Biologic Impact (Pharmacodynamics) of Repeated Injections and Increasing Amounts of UPB-101 in Asthmatics

Study Overview
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Brief Summary
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The goals of this clinical study are to assess the safety, tolerability, blood levels, and disease impact of UPB-101 when given to adults with mild asthma. Eligible participant will be consecutively assigned to 1 of 3 to 5 planned treatment groups. Each treatment group will consist of 8 individuals, six of whom will receive active drug (UPB-101) and 2 who will be given placebo. Neither the study doctors nor the participants will know which participants were assigned to active study drug and which were assigned to placebo. The study will be performed at 3-4 experienced research sites in the United Kingdom.

Detailed Description
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This is a two-part phase 1b, multi-center randomized, double-blind (Investigator and Subject blinded; Sponsor unblinded), placebo-controlled, multiple ascending-dose study to assess the safety, tolerability, immunogenicity, pharmacokinetics (PK), and pharmacodynamics (PD) of UPB-101 administered subcutaneously (SC) to adult subjects with asthma. The study consists of Part A and Part B. Part A includes 3 cohorts with pre-set dosing regimens. Part B (optional) includes up to 2 additional cohorts whose doses and dosing intervals will be decided based upon the safety, PK, and PD results from Part A (i.e., an adaptive design), as applicable. The regimens selected for Part B will not exceed the exposures (i.e., doses and/or dosing intervals) included in Part A. Eight subjects will be randomized per cohort (6 active, 2 placebo). Thus, a total of approximately 24 to 40 subjects will be enrolled in the study with 24 subjects in Part A and up to 16 if Part B cohorts are implemented.

Official Title
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A Phase 1, Randomized, Double-blind, Placebo-controlled, Multiple Ascending-Dose Study to Assess the Safety, Tolerability, Immunogenicity, Pharmacokinetics and Pharmacodynamics of UPB-101 in Subjects With Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: UPB-101
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 18 to 60, and has physician-diagnosed asthma Body mass index (BMI) between 18 and 35 kg/m2 Blood eosinophil cell count ≥200 (OR ≥150 combined with fractional exhaled nitric oxide [a measure of lung airway inflammation] >25) at one screening visit and ≥150 at the other screening Agrees to follow the required contraceptive techniques Female or male participant agrees not to donate eggs or sperm, respectively, for a period of 120 days after the last dose of the study drug Able to perform spirometry (breathing tests) Asthma and non-biologic asthma medication have been stable for the past 2 months Exclusion Criteria: Employee, consultant, and/or immediate family member of any person involved in the conduct of the study Previous exposure to the study drug or known allergy/sensitivity to any of its ingredients Pregnant or breastfeeding female Unable to fast and avoid strenuous exercise for 9 hours prior to each site visit Serious allergic reaction to any injected drug Significantly abnormal clinical laboratory test results or a significant medical condition Recently donated blood (including blood products) or experienced significant loss of blood Has pacemaker or a significantly abnormal electrocardiogram An active or a serious infection in the past 8 weeks Poorly-controlled diabetes or abnormal kidney function Tests positive to illicit drugs or nicotine and cannot limit alcohol consumption Tests positive for human immunodeficiency virus antibodies (HIV), hepatitis B, hepatitis C antibodies, or tuberculosis Received any vaccine within the past month Received any immunosuppressant therapies in the past Received an antibody or therapeutic biologic product in the last 6 months Received steroids (other than inhaled) in the past 2 months Participated recently in a clinical study Current tobacco smokers or has smoked within the last year Tested positive for COVID-19 in the past month

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active substance 1<br>UPB-101 Cohort 1 | Drug: UPB-101<br>* Subcutaneous injection<br>* Other names: Formerly ASP7266;Drug: Placebo<br>* Subcutaneous injection<br>* Other names: 0.9% saline solution;|
| Experimental: Active substance 2<br>UPB-101 Cohort 2 | Drug: UPB-101<br>* Subcutaneous injection<br>* Other names: Formerly ASP7266;Drug: Placebo<br>* Subcutaneous injection<br>* Other names: 0.9% saline solution;|
| Experimental: Active substance 3<br>UPB-101 Cohort 3 | Drug: UPB-101<br>* Subcutaneous injection<br>* Other names: Formerly ASP7266;Drug: Placebo<br>* Subcutaneous injection<br>* Other names: 0.9% saline solution;|
| Experimental: Active Substance 4<br>UPB-101 Cohort 4 | Drug: UPB-101<br>* Subcutaneous injection<br>* Other names: Formerly ASP7266;Drug: Placebo<br>* Subcutaneous injection<br>* Other names: 0.9% saline solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-emergent adverse events and serious adverse events |  | Baseline through 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of anti-drug antibodies |  | Baseline through 24 weeks | 
| Titer of anti-drug antibodies |  | Baseline through 24 weeks | 
| Maximum observed concentration of UPB-101 |  | Baseline through 24 weeks | 
| Time to maximum observed concentration of UPB-101 |  | Baseline through 24 weeks | 
| Area under the concentration-time curve under one dosing interval of UPB-101 |  | Baseline through 24 weeks |