Clinical trial NCT05448651: Safety and Biologic Impact (Pharmacodynamics) of Repeated Injections and Increasing Amounts of UPB-101 in Asthmatics
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Lead sponsor: Upstream Bio Inc.
Sponsor class: INDUSTRY
First posted: 2022-07-07
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Male or female, aged 18 to 60, and has physician-diagnosed asthma
2. Body mass index (BMI) between 18 and 35 kg/m2
3. 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
4. Agrees to follow the required contraceptive techniques
5. 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
6. Able to perform spirometry (breathing tests)
7. Asthma and non-biologic asthma medication have been stable for the past 2 months

Exclusion Criteria:

1. Employee, consultant, and/or immediate family member of any person involved in the conduct of the study
2. Previous exposure to the study drug or known allergy/sensitivity to any of its ingredients
3. Pregnant or breastfeeding female
4. Unable to fast and avoid strenuous exercise for 9 hours prior to each site visit
5. Serious allergic reaction to any injected drug
6. Significantly abnormal clinical laboratory test results or a significant medical condition
7. Recently donated blood (including blood products) or experienced significant loss of blood
8. Has pacemaker or a significantly abnormal electrocardiogram
9. An active or a serious infection in the past 8 weeks
10. Poorly-controlled diabetes or abnormal kidney function
11. Tests positive to illicit drugs or nicotine and cannot limit alcohol consumption
12. Tests positive for human immunodeficiency virus antibodies (HIV), hepatitis B, hepatitis C antibodies, or tuberculosis
13. Received any vaccine within the past month
14. Received any immunosuppressant therapies in the past
15. Received an antibody or therapeutic biologic product in the last 6 months
16. Received steroids (other than inhaled) in the past 2 months
17. Participated recently in a clinical study
18. Current tobacco smokers or has smoked within the last year
19. Tested positive for COVID-19 in the past month

Primary outcomes:
measure: Number of Treatment-emergent Adverse Events and Serious Adverse Events
timeFrame: Baseline through 24 weeks
Secondary outcomes:
measure: Incidence of Anti-drug Antibodies
timeFrame: Baseline through Week 32
measure: Maximum Observed Concentration of UPB-101
timeFrame: First Dose = Day 1. Last Dose = Baseline through 32 weeks.
measure: Time to Maximum Observed Concentration of UPB-101
timeFrame: Baseline through 32 weeks
measure: Area Under the Concentration-time Curve Under One Dosing Interval of UPB-101
timeFrame: Baseline through 32 weeks
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Hammersmith Medicines Research
city: London
country: United Kingdom
facility: Queen Anne Street Medical Centre
city: London
country: United Kingdom
facility: Richmond Pharmacology
city: Manchester
country: United Kingdom
facility: Medicines Evaluation Unit
Study officials:
affiliation: Upstream Bio
name: Sumathi Sivapalasingam, MD
role: STUDY_DIRECTOR
References: