A Study to Investigate the Efficacy and Safety of Verekitug (UPB-101) in Adult Participants with Severe Asthma (VALIANT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Upstream Bio Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

19 Jun 2024 → 2 Mar 2026

Decision date (initial)

2024-04-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Dose response, Safety, Pharmacodynamic, Pharmacokinetic, Therapy

To assess the effect of verekitug (UPB-101) on asthma exacerbations compared to placebo

Secondary objectives 3

1. To assess the effect of verekitug (UPB-101) on lung function compared to placebo
2. To assess the effect of verekitug (UPB-101) on an airway inflammation biomarker compared to placebo
3. To assess the effect of verekitug (UPB-101) on asthma control compared to placebo

Conditions and MedDRA coding

Severe Asthma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. 1. Participant has signed, dated, and received a copy of the approved written informed consent form (ICF)
2. 2. Participant is aged 18 to 80 years of age (inclusive) at the time of signing the ICF
3. 3. Body mass index between 18 and 40 kg/m2 (inclusive) at Visit 1
4. 4. Participant has physician-diagnosed asthma for at least 12 months prior to Visit 1
5. 5. 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
6. 6. 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))
7. 7. 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
8. 8. Participant has Asthma Control Questionnaire-6 (ACQ-6) score ≥ 1.5 at Visit 1 and Visit 3
9. 9. 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
10. 10. Participant must have a morning pre-BD FEV1 value of ≥ 30% and ≤ 80%, predicted at Visit 2
11. 11. 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
12. 12. Minimum of 4 days with complete (evening and subsequent morning) daily diary in the 7 days prior to Visit 3
13. 13. 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)
14. 14. Acceptable inhaler, peak flow meter, and spirometry techniques
15. 15. Contraceptive use by participant must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

Exclusion criteria 34

1. 1. Inpatient hospitalization due to asthma at any time within 4 weeks prior to Visit 1 or during the Screening/Run-in Period
2. 2. 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
3. 3. Previous exposure to verekitug (UPB-101) or known allergy/sensitivity to any of its excipients
4. 4. 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.
5. 5. 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
6. 6. Any experimental antibodies within 5 half-lives or within 24 weeks before Visit 1 if the half-life was unknown
7. 7. Allergen immunotherapy (unless maintenance dose) within 12 weeks prior to Visit 1 or plans to begin therapy or change dosing during the study
8. 8. 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
9. 9. 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
10. 10. Administration of the T2 cytokine inhibitor suplatast tosilate within 2 weeks prior to Visit 1
11. 11. Treatment with a live (attenuated) vaccine within 12 weeks before Visit 3
12. 12. Any vaccination within the Screening/Run-in Period
13. 13. Patients on or initiation of bronchial thermoplasty before Visit 1 or plan to begin therapy during Screening or the Treatment Period
14. 14. Aspirin desensitization therapy (unless maintenance) or initiation of new aspirin desensitization within 12 weeks prior to Visit 1
15. 15. History of documented immune complex disease (Type III hypersensitivity reactions) or anaphylaxis following any biologic therapy
16. 16. 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.
17. 17. 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
18. 18. 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
19. 19. 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
20. 20. Evidence of active or suspected bacterial, viral, fungal, or parasitic infections within 2 weeks prior to Visit 1
21. 21. History compatible with or diagnosis of a parasitic infection and has not been treated or has not responded to standard of care therapy
22. 22. Type I or II diabetes under poor glucose control, as assessed by the Investigator
23. 23. Estimated glomerular filtration rate of < 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration equation.
24. 24. 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.
25. 25. 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
26. 26. Immunodeficiency disorder or positive human immunodeficiency virus (HIV) testing
27. 27. 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.
28. 28. 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.
29. 29. History of chronic alcohol or substance use disorder within 12 months prior to Visit 1
30. 30. Current tobacco smokers, nicotine vapers (including electronic cigarettes), snuff users or participants with a smoking history ≥ 10 pack years
31. 31. Positive coronavirus disease 2019 (COVID-19) test with lower respiratory tract symptoms within 28 days before Visit 1
32. 32. 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
33. 33. 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
34. 34. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. AAER over 60 weeks of treatment Annualized Asthma Exacerbation Rate (AAER) over 60 weeks of treatment

Secondary endpoints 3

1. Change from baseline to Week 60 in pre-BD FEV1
2. Change from baseline to Week 60 in FeNO
3. Change from baseline to Week 60 in ACQ-6

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Upstream Bio Inc.

Sponsor organisation

Upstream Bio Inc.

Address

890 Winter Street Suite 200

City

Waltham

Postcode

02451-1490

Country

United States

Scientific contact point

Organisation

Upstream Bio Inc.

Contact name

James Lee

Public contact point

Organisation

Upstream Bio Inc.

Contact name

James Lee

Third parties 4

Locations

6 EU/EEA countries · 42 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 132 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications