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

Phase 1

Completed

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

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Number of Treatment-emergent Adverse Events and Serious Adverse Events	Baseline through 24 weeks	Overall Summary of Treatment-emergent Adverse Events (TEAEs) and Adverse Events (AEs) up to Week 24 (Safety Population)

Secondary Outcome Measures

Name	Time	Method
Incidence of Anti-drug Antibodies	Baseline through Week 32	Blood samples were analyzed for the presence of ADAs using validated assays. Low titer ADA responses were detected toward the end of the concentration vs time profile. There was no evident effect of ADAs on drug exposure and no immune-related adverse events
Maximum Observed Concentration of UPB-101	First Dose = Day 1. Last Dose = Baseline through 32 weeks.	Blood samples were collected and analyzed using a validated assay to determine the Cmax (ug/mL) of UPB-101. The pharmacokinetic (PK) parameters were estimated using non-compartmental analysis.
Time to Maximum Observed Concentration of UPB-101	Baseline through 32 weeks	Blood samples were collected and analyzed using a validated assay to determine the Tmax (days) of UPB-101. The pharmacokinetic (PK) parameters were estimated using non-compartmental analysis.
Area Under the Concentration-time Curve Under One Dosing Interval of UPB-101	Baseline through 32 weeks	Blood samples were collected and analyzed using a validated assay to determine the AUClast (d.ug/mL) of UPB-101. The pharmacokinetic (PK) parameters were estimated using non-compartmental analysis.

Locations (4): Hammersmith Medicines Research
🇬🇧
London, United Kingdom
Queen Anne Street Medical Centre
🇬🇧
London, United Kingdom
Richmond Pharmacology
🇬🇧
London, United Kingdom
Medicines Evaluation Unit
🇬🇧
Manchester, United Kingdom
Hammersmith Medicines Research
🇬🇧London, United Kingdom