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

Asthma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05448651
• Other study ID #: UPB-CP-01
• Status: Completed
• Phase: Phase 1
• Start date: July 8, 2022
• Est. completion date: October 5, 2023

Study information

• Verified date: October 2023
• Source: Upstream Bio Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: October 5, 2023
• Est. primary completion date: August 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• UPB-101
Subcutaneous injection
• Placebo
Subcutaneous injection

Locations

Country	Name	City	State
United Kingdom	Hammersmith Medicines Research	London
United Kingdom	Queen Anne Street Medical Centre	London
United Kingdom	Richmond Pharmacology	London
United Kingdom	Medicines Evaluation Unit	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Upstream Bio Inc.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-emergent adverse events and serious adverse events		Baseline through 24 weeks
Secondary	Incidence of anti-drug antibodies		Baseline through 24 weeks
Secondary	Titer of anti-drug antibodies		Baseline through 24 weeks
Secondary	Maximum observed concentration of UPB-101		Baseline through 24 weeks
Secondary	Time to maximum observed concentration of UPB-101		Baseline through 24 weeks
Secondary	Area under the concentration-time curve under one dosing interval of UPB-101		Baseline through 24 weeks