Inclusion Criteria:

Informed Consent

• Participant has signed, dated, and received a copy of the Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent form (ICF) as described in Appendix 1 (Section 10.1.3), which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Age and Body Mass

• Participant is aged 18 to 75 years of age (inclusive) at the time of signing the ICF.
• Body mass index between 18 and 40 kg/m^2 (inclusive) at Visit 1.

Type of Participant and Disease Characteristics\

• 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:
  • Historical reversibility of FEV1 ≥ 12% and ≥ 200 mL in the 12 months prior to Visit 1; OR
  • Reversibility of FEV1 ≥ 12% and 200 mL, post-BD (15-30 minutes after administration of four puffs of albuterol/salbutamol) at Visit 2:
    • Note: An additional visit can be scheduled prior to Visit 3 to repeat this assessment if this criterion is not met 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:
  • Medium dose ICS and a second asthma controller (long-acting beta agonists [LABA], leukotriene receptor antagonists [LTRA], theophylline, OCS). Note: Medium dose ICS is defined as total daily dose of ≥ 250 to 500 μg fluticasone or equivalent. Equivalent ICS doses will be based upon the GINA guidelines (GINA 2023; Section 10.5). The ICS can be contained within an ICS/LABA combination product;
  • High-dose ICS (with or without a second asthma controller):
    • Note: High-dose ICS is defined as total daily dose of > 500 μg fluticasone or equivalent. Equivalent ICS doses will be based upon the GINA guidelines (GINA 2023; Section 10.5). The ICS can be contained within an ICS/LABA combination product.
• Participant has documented (defined below† ) history within 12 months of Visit 1 of:
  • ≥ 2 asthma exacerbation events as defined below* under (a) or (b); OR
  • 1 asthma exacerbation event as defined below* under (a) or (b) combined with a FeNO of ≥ 50 ppb at Visit 1; OR
  • 1 asthma exacerbation event as defined below* under (c). *An asthma exacerbation is defined as either: 
    • Worsening of asthma that required treatment with systemic (oral or IV) corticosteroids for at least three consecutive days or a single depo-injectable dose of corticosteroids;
      • NOTE: For participants receiving a stable maintenance dose of OCS, a temporary increase for at least three consecutive days over and above the stable existing maintenance dose qualifies as an exacerbation; OR
        • An emergency room (ER) visit or an urgent care visit (defined as evaluation and treatment for < 24 hours for asthma) that required systemic (oral or IV) corticosteroids (as per above); OR
        • An admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for ≥ 24 hours for asthma. Also see Exclusion Criterion #1 (Section 5.2) regarding inpatient hospitalization due to asthma within 1 month prior to Screening/Run-in Visit 1. †Acceptable documentation of asthma exacerbation events is described in Section 8.2.1.
• 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:
  • Daytime or night-time Asthma Symptom Diary (ASD) Score of ≥ 1 for at least 2 days;
  • Reliever medication (e.g., short-acting beta-agonists [SABA] or as needed ICS/LABA added to background medications) use for at least 3 days to treat increased asthma symptoms and not for prophylactic purposes;
  • 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:
  • Note: An additional visit can be scheduled prior to Visit 3 to repeat this assessment if this criterion is not met 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. Note: A compliance day requires completion of evening diary and subsequent morning diary such that an ASD daily score can be calculated. The Run-In Period for this criterion is defined as the period between diary assignment on Visit 2 (evening assessment) and Visit 3 (morning assessment).
• Minimum of 4 days with complete (evening and subsequent morning) daily diary in the 7 days prior to Visit 3 (evening assessment Day –7 to morning assessment on day of 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):
  • Note: Days with missing diary data will be treated as non-compliant for this criterion.
• Acceptable inhaler, peak flow meter, and spirometry techniques.

Contraceptive/Barrier Requirements

• Contraceptive use by participant must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies:
  • NOTE: The reliability of sexual abstinence for participant enrolment eligibility needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception. Participants capable of producing sperm:
    • Agree to refrain from donating sperm during the intervention period and for a period of 120 days after the last dose of study intervention or at the Final Visit, whichever occurs last; AND
    • Agree to follow the contraceptive guidance in Appendix 4 of this protocol during the intervention period and for a period of 120 days after the last dose of study intervention or at the Final Visit, whichever occurs last; AND
    •  Agree to use a condom when engaging in any activity that allows for passage of ejaculate to another person during the intervention period and for a period of 120 days after the last dose of study intervention or at the Final Visit, whichever occurs last.
  • Participants of childbearing potential:
    • Agree to refrain from donating eggs for a period of 120 days after the last dose of study intervention or at the Final Visit, whichever occurs last;
    • Participants are eligible to participate if they are not pregnant (see Appendix 4), not breastfeeding, and at least one of the following conditions applies:
      • Not a participant of childbearing potential (POCBP) as defined in Appendix 4; OR
      • A POCBP who agrees to follow the contraceptive guidance in Appendix 4 during the intervention period and for 120 days after the last dose of study intervention or at the Final Visit, whichever occurs last.

Exclusion Criteria:

Medical Conditions '

• Inpatient hospitalization due to asthma (as defined above in Inclusion Criterion #7) at any time within 4 weeks prior to Visit 1 or during the Screening/Run-in Period.

Prior/Concomitant Therapy

• Concurrent participation in a clinical study or has been treated with an investigational drug within 28 days or five 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 for asthma treatment for which the appropriate 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 halflife 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. Note: Stable maintenance doses of allergen immunotherapy within 12 weeks prior to Visit 1 are allowed.
• 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, longacting 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: 
  • Note: Stable maintenance doses of aspirin desensitization therapy within 12 weeks prior to Visit 1 are allowed.
• History of documented immune complex disease (Type III hypersensitivity reactions) or anaphylaxis following any biologic therapy.

Concomitant Conditions and Disease

• 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: 
  • Note: These include:
    • Clinically significant abnormal ECG at randomization that may affect the conduct of the study in the judgment of the Investigator, prolonged QT corrected for heart rate (QTc) interval (male > 450 msec, female > 470 msec, Fridericia correction);
    • 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;
    • And 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 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. Note: Out of range screening values may be repeated one time per Investigator’s discretion.
• 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 (e.g., gastroesophageal reflux and vocal cord paralysis/dysfunction).
• Evidence of active or suspected bacterial, viral, fungal, or parasitic infections within 2 weeks prior to Visit 1 (e.g., sinusitis, common cold, viral syndrome, flu-like symptoms).
• 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 m^2 using the Chronic Kidney Disease Epidemiology Collaboration equation with correction factor for Black/African American participants. Note: Non-clinically significant out of range value may be repeated one time per Investigator’s discretion.
• History of malignancy of any type, other than 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 for human immunodeficiency virus (HIV) antibodies.
• Positive hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibodies (HCV Ab).
• Known or suspected active tuberculosis, or untreated or inadequately treated latent tuberculosis at Visit 1. Tuberculosis screening may be performed if required based on local guidelines. Treatment for active tuberculosis should be completed > 12 months prior to Visit 1.
• 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. Note: Former nicotine smokers with a smoking history of < 10 pack years, former nicotine vapers and former snuff users must have stopped for at least 6 months prior to Visit 1 to be eligible.
• 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.

Administrative

• 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.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 12/19/23. Questions regarding updates should be directed to the study team contact.