Compare the safety and efficacy of two different oral vapendavir doses with placebo in order to determine the appropriate dose of vapendavir to reduce the severity and/or duration of respiratory symptoms associated with RV infections in patients with COPD.

Inclusion

Sign informed consent for study participation and medical records release (if needed).

Male or female age ≥40 years and ≤85 years at the time of signing the informed consent at Screening.

If sexually active and/or of child-bearing potential (both females and males), must agree to use a highly effective form of contraception at the time of randomization until 30 days (females) or 90 days (males) after the last dose. Female participants may not use hormonal birth control as a sole method. Participants will be asked to commit to this criterion at screening even though it does not need to be implemented until treatment is received. See Section 11.2 below.

Confirmed diagnosis of COPD, defined as chronic cough, sputum production, and/or dyspnea with airflow obstruction which is not fully reversible (that is, post bronchodilator FEV1/FVC ratio <0.70 and post bronchodilator FEV1 ≥20% and <80% of predicted normal value).

History of AECOPD with at least 1 documented AECOPD within 1 year of Screening.

• AECOPD is defined as an event characterized by dyspnea and/or cough and increased sputum purulence/change in sputum color that worsens over several days, and requires at least one of the following for at least 2 days:
• Increase frequency or dose of beta agonist(s), oxygen, breathing treatments or chronic COPD medications (Mild Exacerbation)
• Use of oral or systemic steroids (Moderate Exacerbation), or
• Use of Antibiotics (Moderate Exacerbation), or
• Emergency room visit or hospitalization (Severe Exacerbation). CAT score ≥10 at screening. Able to comply with all study requirements, including the use of a mobile application to complete daily PROs, perform nasal swabs at home, and able to assess when they have cold symptoms.

Interacts with people at least twice a week without a mask (e.g., grocery shopping, dinner with grandchildren, eating at a restaurant, going to the movies, etc.) or are living in a multigenerational home.

Inclusion criteria to be assessed only at Randomization:

If on stable COPD maintenance therapy this should be stable for at least 2 months prior to randomization. Changes allowed with Sponsor approval (i.e., change within same class due to financial considerations and clinically stable).

Clinically stable with no other exacerbations or respiratory infections (viral or bacterial) within 2 months prior to randomization.

The presence of RV (without a co-infection) at the time of randomization based on an approved molecular diagnostic test.

To be randomized, participants must have at least 3 E-RS scores completed within the previous 35 days to establish a PSB.

Exclusion

Pregnant or nursing or expected to become pregnant during the study period. Experiencing a current/active or prior exacerbation within 2 months of the Screening Visit (these participants should be rescreened after the exacerbation has been resolved for two months).

Participants with other primary causes of chronic airflow limitation:

- Including but not limited to: asthma alone (COPD with asthmatic features is acceptable), CF, bronchiolitis obliterans, fibrosis such as TB, IPF, non-CF bronchiectasis with multi-lobe involvement or other major respiratory diagnosis (e.g., allergic bronchopulmonary aspergillosis), etc.

Any disorder, for example, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric impairment that is not medically stable, or other major physical impairment that is not considered by the investigator medically stable/controlled.

Participants with hepatitis B are excluded. Participants on a stable treatment for HIV can be permitted with permission from the medical monitor. Participants with hepatitis C should be treated and confirmed HCV RNA negative prior to enrollment. (Testing performed at the Screening Visit).

In the Investigator's opinion, the participant has any clinically significant laboratory abnormality including an abnormality that indicates clinically significant hematologic, hepatobiliary, or renal disease.

Presence of clinically significant out-of-range cardiac interval on the screening ECG including a QTcF > 450 msec (men) and a QTcF > 460 msec (women).

Medications or other non-medicinal products that could be impacted by CYP3A4, CYP2C8, or CYP2C19 induction and have serious complications for the participant within the treatment period.

Medications that are potent CYP2C8, CYP3A4 or CYP2C19 inducers that would reduce exposures of VPV.

Medications that are potent CYP2C8, CYP3A4, or CYP2C19 inhibitors that would increase exposures of VPV.

Medications that are substrates of MATE1, OAT3, P-gp, and BCRP for which elevated concentrations are associated with serious and/or life-threatening reactions.

Use of either of the following treatments:

• Chronic oral/systemic steroids >10 mg per day (inhaled corticosteroids are permitted).
• Continuous oxygen via nasal cannula of >2 L/min at the time of Screening or during the Asymptomatic Phase. (Participants on continuous oxygen may have the rate increased during physical exercise/ exertion or to cover any situationally induced decompensation, so long as the participant will resume a continuous rate of ≤2 L/min thereafter).

Participation in another investigational drug study within 5 half-lives prior to Screening and during the study is prohibited. This includes approved drugs being evaluated for a new indication. Observational studies are permitted.

Participants who have taken VPV in another clinical trial.

Exclusion criteria to be assessed only at Randomization:

It is already determined, based on the Investigator's clinical judgement, that the participant will likely need antibiotics and/or oral steroids at the Day 1 Randomization Visit.

On or within 7 days prior to randomization, there is another active diagnosed infection with viral or bacterial pathogens (i.e., urinary tract infection, cellulitis, etc.) that requires treatment.