Efficacy and Safety Evaluation of Verekitug (UPB-101) in Adults with Severe Asthma: A Phase 2 Randomized, Double-blind, Placebo-controlled Study
- Trial ID
- 2023-507410-27-00
- Protocol
- UPB-CP-04
- Sponsor
- Upstream Bio Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the effect of **verekitug (UPB-101)** on asthma exacerbations compared to placebo in adult participants with severe asthma. This is clinically relevant as reducing asthma exacerbations can significantly improve patient outcomes and quality of life, as well as reduce healthcare utilization and costs associated with severe asthma management.
Secondary objectives include:
- Assessing the effect of verekitug (UPB-101) on lung function compared to placebo, which is important for understanding the potential benefits of the treatment on respiratory capacity and overall pulmonary health.
- Evaluating the effect of verekitug (UPB-101) on an airway inflammation biomarker compared to placebo, providing insights into the drug's impact on underlying inflammatory processes associated with severe asthma.
- Assessing the effect of verekitug (UPB-101) on asthma control compared to placebo, which is crucial for determining the treatment's efficacy in managing symptoms and improving daily functioning for patients.
Participants
The clinical trial investigating the effects of verekitug (UPB-101) on asthma exacerbations compared to placebo involves a total of **299 participants**. The study population includes both **male and female** subjects, aged between **18 to 80 years**, who have been diagnosed with **severe asthma**. Participants were selected based on specific inclusion criteria, such as having a physician-diagnosed asthma for at least 12 months and a body mass index between 18 and 40 kg/m². The trial also considers lifestyle factors, requiring participants to have stable asthma medication regimens and compliance with daily diaries. The study includes a vulnerable population, ensuring that all participants have provided informed consent. Key inclusion criteria include evidence of bronchodilator reversibility and a history of asthma exacerbations. The trial does not specify any particular dietary or physical activity requirements for participants.
Plans and Procedures
The clinical trial is a **Phase 2**, randomized, double-blind, placebo-controlled, multi-center study designed to evaluate the efficacy and safety of Verekitug (UPB-101) in adult participants with **severe asthma**. The primary objective is to assess the effect of Verekitug on asthma exacerbations compared to placebo. The trial is expected to last approximately 60 weeks, with participant recruitment anticipated to begin in June 2024 and conclude by February 2026.
Participants will be randomly assigned to receive either the investigational product, Verekitug, or a matching placebo, both administered via subcutaneous injection. The study will include several key visits: an initial screening visit to confirm eligibility, followed by a series of follow-up visits to monitor safety and efficacy, and a final end-of-study visit. The inclusion criteria require participants to be between 18 and 80 years of age, with a physician-diagnosed history of asthma for at least 12 months, and specific lung function parameters. Participants must also demonstrate compliance with background asthma medication and daily diary entries during the run-in period.
The expected duration of participant involvement is approximately 60 weeks, during which they will undergo regular assessments to evaluate lung function, asthma control, and any adverse events. Conditions that may lead to early termination from the study include non-compliance with study procedures, withdrawal of consent, or any adverse event that poses a risk to the participant's health. The primary endpoint is the annualized asthma exacerbation rate over the treatment period, with secondary endpoints including changes in pre-bronchodilator FEV1, FeNO levels, and ACQ-6 scores from baseline to week 60.
Treatment
The clinical trial involves the administration of **Verekitug (UPB-101)**, a **human IgG1 kappa monoclonal antibody against CRLF2**. This experimental medication is provided in the form of a **solution for injection**. The route of administration is **subcutaneous use**. The dosing schedule is designed to ensure participant safety and compliance, with a maximum treatment period of 60 days. The specific dosage and frequency of administration are determined based on the study protocol, although the maximum daily and total dose amounts are not specified in the provided data. The medication is developed by UPSTREAM BIO, INC., and is not a pediatric formulation.
In addition to the experimental treatment, the study includes a **placebo** group. The placebo is a matching solution for subcutaneous injection, designed to have no active treatment effect. This ensures the study maintains a double-blind, placebo-controlled design, allowing for an accurate assessment of the efficacy and safety of Verekitug (UPB-101) in comparison to the placebo. The placebo is administered in the same manner as the experimental drug, with the same maximum treatment period of 60 days. Participant compliance is monitored throughout the study to ensure adherence to the dosing schedule and to maintain the integrity of the trial results.
Efficacy
The efficacy of Verekitug (UPB-101) in the treatment of severe asthma will be assessed through a series of predefined endpoints. The primary endpoint is the **Annualized Asthma Exacerbation Rate (AAER)** over a 60-week treatment period. This endpoint will provide a quantitative measure of the frequency of asthma exacerbations experienced by participants during the trial.
Secondary endpoints include changes from baseline to Week 60 in several key parameters: pre-bronchodilator forced expiratory volume in one second (pre-BD FEV1), fractional exhaled nitric oxide (FeNO), and the Asthma Control Questionnaire-6 (ACQ-6) score. These secondary endpoints will offer additional insights into the treatment's impact on lung function, airway inflammation, and overall asthma control.
Data collection will occur at specified timepoints throughout the trial, with baseline measurements taken prior to the initiation of treatment and subsequent assessments conducted at regular intervals up to Week 60. The use of validated scales and laboratory tests will ensure the reliability and accuracy of the efficacy assessments. The analysis of these parameters will be conducted in a manner consistent with standard clinical trial practices to determine the therapeutic benefit of Verekitug (UPB-101) compared to placebo.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant has signed, dated, and received a copy of the approved written informed consent form (ICF)
- Participant is aged 18 to 80 years of age (inclusive) at the time of signing the ICF
- Body mass index between 18 and 40 kg/m2 (inclusive) at Visit 1
- Participant has physician-diagnosed asthma for at least 12 months prior to Visit 1
- Participant has evidence of bronchodilator (BD) reversibility as documented by either: a) Historical reversibility of FEV1 ≥ 12% and ≥ 200 mL in the 12 months prior to Visit 1; OR b) Reversibility of FEV1 ≥ 12% and 200 mL, post-BD (15-30 minutes after administration of four puffs of albuterol/salbutamol) at Visit 2
- Participant has been on background asthma medication(s) as described below for at least 12 weeks prior to Visit 1, with stable dose regimen for at least 4 weeks prior to Visit 1 and throughout the Screening/Run-in Period: a) Medium dose ICS and at least one additional controller (eg, long-acting beta agonists [LABA], leukotriene receptor antagonists [LTRA], long-acting muscarinic antagonist [LAMA], theophylline, OCS); b) High-dose ICS (with or without additional asthma controller(s))
- Participant has documented (defined below†) history within 12 months of Visit 1 of: a) ≥ 2 asthma exacerbation events, OR b) 1 asthma exacerbation event combined with a FeNO of ≥ 50 ppb at Visit 1, OR c) 1 asthma exacerbation event
- Participant has Asthma Control Questionnaire-6 (ACQ-6) score ≥ 1.5 at Visit 1 and Visit 3
- At least one of the following conditions between Visit 2 and Visit 3: a) Daytime or night-time Asthma Symptom Diary (ASD) Score of ≥ 1 for at least 2 days b) Reliever medication (e.g., short-acting beta-agonists [SABA] or as needed ICS/LABA or ICS/SABA added to background medications) use for at least 3 days to treat increased asthma symptoms and not for prophylactic purposes c) At least one night-time awakening due to asthma
- Participant must have a morning pre-BD FEV1 value of ≥ 30% and ≤ 80%, predicted at Visit 2
- Minimum compliance with daily diary during the Run-In Period, defined as a minimum of 12 fully compliant days in the 15 days up to and including the day of Visit 3
- Minimum of 4 days with complete (evening and subsequent morning) daily diary in the 7 days prior to Visit 3
- Minimum compliance with background asthma medication(s) as captured in the diary during the Run-in Period (having a minimum of 12 fully compliant dosing days in the 15 days up to and including Visit 3)
- Acceptable inhaler, peak flow meter, and spirometry techniques
- Contraceptive use by participant must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
Exclusion Criteria
- Inpatient hospitalization due to asthma at any time within 4 weeks prior to Visit 1 or during the Screening/Run-in Period
- Concurrent participation in a clinical study or has been treated with an investigational drug within 28 days or 5 half-lives, whichever is longer, prior to Visit 1
- Previous exposure to verekitug (UPB-101) or known allergy/sensitivity to any of its excipients
- Previous biologics, including those for asthma treatment, for which a 5 half-life washout period is not fulfilled prior to Visit 1. If the half-life is not known, a 24-week washout period prior to Visit 1 should be applied.
- Biologic therapy or systemic immunosuppressant to treat inflammatory disease or autoimmune disease within 24 weeks or 5 half-lives prior to Visit 1, whichever is longer, with the exception of OCS. Treatment with cyclophosphamide and rituximab within 12 months of Visit 1
- Any experimental antibodies within 5 half-lives or within 24 weeks before Visit 1 if the half-life was unknown
- Allergen immunotherapy (unless maintenance dose) within 12 weeks prior to Visit 1 or plans to begin therapy or change dosing during the study
- For participants receiving background medium dose ICS and a second asthma controller or high dose ICS, additional asthma background medication(s) (e.g., LTRA, theophylline, long-acting muscarinic antagonist [LAMA]) for which the dose has not been stable for at least 4 weeks prior to Visit 1
- For participants taking OCSs, the dose has not been stable for at least 2 weeks prior to Visit 1 and/or is > 10 mg daily, or > 20 mg every other day
- Administration of the T2 cytokine inhibitor suplatast tosilate within 2 weeks prior to Visit 1
- Treatment with a live (attenuated) vaccine within 12 weeks before Visit 3
- Any vaccination within the Screening/Run-in Period
- Patients on or initiation of bronchial thermoplasty before Visit 1 or plan to begin therapy during Screening or the Treatment Period
- Aspirin desensitization therapy (unless maintenance) or initiation of new aspirin desensitization within 12 weeks prior to Visit 1
- History of documented immune complex disease (Type III hypersensitivity reactions) or anaphylaxis following any biologic therapy
- Participants meeting any of the following criteria: • Prolonged QT corrected for heart rate (QTcF) interval (male >450 msec, female >470 msec, Fridericia correction); for participants with a bundle branch block or cardiac pacemaker, a QTcF interval of >480 ms; any other clinically significant abnormal ECG from screening to randomization that may affect the conduct of the study in the judgment of the Investigator • Any of the following in the previous 6 months prior to Visit 1: acute myocardial infarction, transient ischemic attack or stroke, hospitalization for any cardiovascular or cerebrovascular event; • Cardiac arrhythmias including paroxysmal (e.g., intermittent). Patients with persistent atrial fibrillation as defined by continuous atrial fibrillation for at least 6 months and controlled with a rate control strategy (i.e., selective beta blocker, calcium channel blocker, pacemaker placement, digoxin or ablation therapy) and stable appropriate level of anticoagulation for at least 6 months may be considered for inclusion. • Any other abnormal medical history, physical finding, or safety finding that in the opinion of the Investigator may obscure the study data or interfere with the participant’s safety.
- Any clinical laboratory test result outside of the reference ranges considered by the Investigator as clinically significant and that may obscure the study data or interfere with the participant’s safety
- Allergic granulomatous angiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener’s granulomatosis), Young’s syndrome, Kartagener’s syndrome or other dyskinetic ciliary syndromes, concomitant cystic fibrosis
- Participant with a history or evidence of a clinically significant pulmonary condition (other than asthma), including significant restrictive findings on pulmonary function testing, chronic bronchitis, emphysema, bronchiectasis, pulmonary fibrosis, or any other related condition that may obscure the study data
- Evidence of active or suspected bacterial, viral, fungal, or parasitic infections within 2 weeks prior to Visit 1
- History compatible with or diagnosis of a parasitic infection and has not been treated or has not responded to standard of care therapy
- Type I or II diabetes under poor glucose control, as assessed by the Investigator
- Estimated glomerular filtration rate of < 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration equation.
- History of malignancy of any type, other than curatively-treated in situ cervical cancer or surgically excised non-melanomatous skin cancers, within 5 years before Visit 1.
- Participant underwent surgery requiring general anesthesia, within 8 weeks of Visit 1, or surgery without full recovery within 4 weeks of Visit 1, or donated blood or blood products (including immunoglobulin), experienced loss of blood ≥ 500 mL, or received blood products within 8 weeks of Visit 1
- Immunodeficiency disorder or positive human immunodeficiency virus (HIV) testing
- Positive hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) and detectable HBV DNA viral load; or positive hepatitis C antibodies (HCV Ab) and detectable HCV RNA viral load.
- All participants will have TB screening performed at Visit 1. For EEA only: Treatment for active tuberculosis (TB) that has been completed within 12 months prior to Visit 1. Participants with a history of active TB treated > 12 months prior to Visit 1 and participants with a history of treated latent TB may be eligible for the study under the following conditions: • Written prior approval by a TB specialist or an infectious disease specialist is required prior to initiation of study drug: o For participants with a prior history of active or latent TB, even if having documented initiation or completion of a full course of anti-TB therapy. o For participants with a positive or indeterminate TB screening test at Visit 1, including those with documented initiation or completion of adequate anti-TB treatment.
- History of chronic alcohol or substance use disorder within 12 months prior to Visit 1
- Current tobacco smokers, nicotine vapers (including electronic cigarettes), snuff users or participants with a smoking history ≥ 10 pack years
- Positive coronavirus disease 2019 (COVID-19) test with lower respiratory tract symptoms within 28 days before Visit 1
- Pregnant or breastfeeding or planning to become pregnant or breastfeed during the study or unwilling to use adequate birth control, if of reproductive potential and sexually active
- Participant is an employee, consultant, and/or immediate family member (i.e., first degree relative, spouse, adoptee, or legal dependent) of the site staff or the Sponsor
- Participant is unreliable, incapable of adhering to the protocol and visit schedule according to the judgment of the Investigator or has any disorder that may compromise their ability to give informed consent
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Not Recruiting | 01 Jun 2024 | 44 |
 Czechia | Not Recruiting | 01 Jun 2024 | 14 |
 Germany | Not Recruiting | 01 Jun 2024 | 32 |
 Italy | Not Recruiting | 01 Jun 2024 | 2 |
 Poland | Not Recruiting | 01 Jun 2024 | 75 |
 Spain | Not Recruiting | 01 Jun 2024 | 15 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
VerekitugUPB-101 | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 00 | 60 | PRD10995765 |
Veritikug (UPB-101) matching solution for subcutaneous injection with no active treatment | Placebo | N/A | SUBCUTANEOUS USE | 00 | 60 | N/A |