Phase 1 controlled multiple ascending dose study of UPB-101 in subjects with asthma
Research type
Research Study
Full 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
IRAS ID
1005306
Contact name
Leslie Dowling
Contact email
Sponsor organisation
Upstream Biotherapeutics Inc.
Eudract number
2022-000132-36
Clinicaltrials.gov Identifier
Research summary
Research Summary
The aim of this clinical study being conducted in asthma patients is to investigate the safety and tolerability of a potential new medicine called UPB-101 being developed as a treatment for asthma. This study will evaluate how well it is tolerated in patients, when given at different doses and at different lengths of time between doses. Patients may receive either UPB-101, or a matching dummy medicine called a placebo, and neither the patients nor the investigators will know which treatment they are receiving (this is called a double-blind study). This ensures that the outcome of the study will not be influenced by patients or study staff knowing who is receiving which treatment. This study will be conducted at three sites in England, and has two parts, A and B. The design of part B will be modified depending upon the outcome of part A. In part A, participants will be given, at specified times, UPB-101 or placebo by injection under the skin (subcutaneously), with the dose and time between doses changing according to the group (cohort) to which a participant is allocated. Participants will undergo physical and clinical examinations to assess their general health and their diagnosis of asthma, and blood samples will also be taken from participants as part of the health checks and to measure the levels of UPB-101 in the blood. The study is open to both male and female participants between 18 and 55 years of age, with a diagnosis of mild-to-moderate asthma and who are stable on their current asthma medication which they would continue taking as usual during the study, who are willing to use contraception for the duration of the study, and who do not have any other illnesses which would exclude them from participating in this clinical study. The length of study participation is up to 35 weeks, including screening (3 wks), dosing (8-12 wks), and post-treatment visits (20-24 wks). The study is funded by the developer, Upstream Bio, and is recruiting at 3-5 sites in the UK.
Summary of Results
Researchers want to see if a new medicine called UPB-101 is safe and effective when used to treat patients with an illness called asthma, which is a swelling (inflammation) in the airways of these patients’ lungs. Some patients with asthma may have a hard time breathing and sometimes have coughing spells. In some patients, asthma can be quite severe and interfere with their daily lives or even be life-threatening. But first, the company must see if UPB-101 is safe and what effects it has on the body by treating a small group of people with asthma.
UPB-101 is a specific type of laboratory-made antibody that is similar to the antibodies our bodies make. UPB-101 was designed to attach to a receptor found on some cells called thymic stromal lymphopoietin receptors (TSLPRs). This attachment blocks the action of TSLP, a protein that plays a role in producing inflammation in patients with asthma. This may help improve breathing in these patients. The researchers wanted to see how different doses of UPB-101 given at different time intervals affects a participant’s immune system, how much UPB-101 ends up in the blood, and how UPB-101 affects different markers of asthma.
During the study, there were 5 groups: 6 participants received 100 mg UPB-101 every 4 weeks for 8 weeks, 6 participants received 200 mg UPB-101 every 4 weeks for 8 weeks, 6 participants received 300 mg UPB-101 at study start and after 12 weeks, 6 participants received 25 mg UPB-101 at the beginning only, 8 participants received placebo. The participants were given information about the study to help them decide if they wanted to join. Participants read a document called an Informed Consent Form or Participant Information Sheet and listened as the document was read in their native language. If they wanted to join, they signed the document. The study doctor or staff at the site checked the participant’s health and took blood samples. Participants with asthma who were otherwise healthy were allowed to proceed. The participants were randomly assigned (like flipping a coin) to 1 of the 5 treatment groups. After receiving treatment and leaving the clinic, the participants came back over the next few months to give blood samples and have their health checked.
This study took place in four clinical study sites in the United Kingdom from 27 June 2022 to 05 October 2023. The study included 32 participants with asthma. Of these: Most were white (23 out of 32) or Asian (5 out of 32). Age ranged from 21 to 55 years. Half were women and half were men (16 of 32 participants each). Participants were in the study for approximately 9 months. The entire study took about 15 months to complete. To see how UPB-101 acted in the body, researchers measured the amount of UPB 101 in blood samples taken at different times during the study, after the first dose and after the last dose.
The results showed that some of the UPB-101 was still in the blood when given to participants every 4 weeks but was mostly gone from the blood when given after 12 weeks. Tests showed that low levels of antibodies to UPB-101 were produced in half of the participants (12 of 24) who received UPB-101 and none of the participants who received placebo. However, these levels of antibodies did not appear to affect the levels of UPB-101 in the blood and did not appear to cause any side effects. UPB-101 caused a decrease in some biomarkers that are elevated in participants with asthma. FeNO (fractional exhaled nitric oxide) levels, a gas measured in a participant’s breath, dropped within 1 week by approximately 40% to 50%. Blood eosinophils, a type of blood cell that can increase inflammation in some patients with asthma, dropped within 1 2 weeks by about 20% to 50%. Blood IgE levels (a type of antibody the immune system makes that can increase symptoms of asthma) and IL-5 levels (a protein that increases blood eosinophil levels) also decreased. The levels of other blood biomarkers and other tests did not appear to change following treatment with UPB-101.
Researchers recorded any medical problems (called side effects) that the participants had while on the study. The most common side effects possibly related to treatment were headache and upper respiratory virus infection, reported by 2 participants each. All side effects were mild to moderate in severity. In addition, skin reactions at the site where the drug was injected occurred in 11 of 32 participants. These skin reactions resolved on their own and were mild to moderate in severity. A side effect is considered serious if it was life-threatening or resulted in hospitalization. participants had any serious side effects. None of the participants dropped out of the study because of side effects.
The results of this study have helped researchers learn more about using UPB-101 given over different time periods to people with asthma and will help researchers design future clinical studies of UPB-101.REC name
Wales REC 1
REC reference
22/WA/0112
Date of REC Opinion
26 May 2022
REC opinion
Further Information Favourable Opinion