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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Placebo; Drug: UPB-101

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Hammersmith Medicines Research
  • London, United Kingdom
    • Richmond Pharmacology
  • London, United Kingdom
    • Queen Anne Street Medical Centre
  • Manchester, United Kingdom
    • Medicines Evaluation Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Upstream Bio Inc.
• Investigators: Study Director: Chaim M Brickman, MD, Upstream Bio

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2022
• Primary Completion (Actual): August 15, 2023
• Study Completion (Actual): October 5, 2023

Study Registration Dates

• First Submitted: June 29, 2022
• First Submitted That Met QC Criteria: July 3, 2022
• First Posted (Actual): July 7, 2022

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: UPB-CP-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No