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

This was 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 included 3 cohorts with pre-set dosing regimens. Part B (optional) included up to 2 additional cohorts whose doses and dosing intervals 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 did not exceed the exposures (i.e., doses and/or dosing intervals) included in Part A. Eight subjects were randomized per cohort (6 active, 2 placebo). Thus, a total of 32 subjects were enrolled in the study with 24 subjects in Part A and 8 in Part B.

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