Rhinovirus Infection
Conditions
Brief summary
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.
Interventions
DRUGVPV 1000 mg
Vapendavir 1000 mg
DRUGVPV 500 mg
Vapendavir 500 mg
OTHERPlacebo
Placebo
Sponsors
Altesa Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluating Respiratory Symptoms (E-RS) | Baseline Period/Asymptomatic Phase: Daily for 12 weeks Treatment/Follow-Up Periods: Daily for up to 42 days | 11-item E RS collected as part of the 14-item EXAcerbations of Chronic pulmonary disease Tool (EXACT PRO®) scale, with data from the additional 3 items from the EXACT PRO scale used for exploratory purposes only. The PSB will be calculated as the mean of the E-RS scores collected in the -35 to -6 days prior to RV symptom onset. If the E-RS score has not returned to PSB at the time of Day 28 Visit, the participant will complete the E-RS daily until Day 42. The questions are asked about how the participant feels today and will be collected at night. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Global Impression of Severity (PGIS) | Baseline Period/Asymptomatic Phase: Daily for 12 weeks Treatment/Follow-Up Periods: Daily for up to 42 days | The PGIS is one question, 'Please rate the overall severity of your respiratory symptoms today? (none, mild, moderate, severe, very severe).' |
| Wisconsin Upper Respiratory Symptom Survey - 11 | Treatment/Follow-up Periods: Daily for 28 days | The questions are asked about how the participant feels today or within the last 24 hours. The questionnaire will be completed at night. |
| Change from Baseline in Respiratory System Resistance at 5 Hz (R5) Measured by Oscillometry | Screening Visit, Day 1, Day 3, Day 7, Day 14, Day 28, Day 42 | Respiratory system resistance at an oscillation frequency of 5 Hz, measured by oscillometry during unforced tidal breathing. R5 reflects total respiratory system resistance and is a measure of overall airway caliber. Values are reported as the mean of at least three technically acceptable measurements, performed according to the 2020 European Respiratory Society / American Thoracic Society technical standards for respiratory oscillometry. Unit of measure: cmH₂O·s/L. |
| Change from Baseline in Respiratory System Resistance at 20 Hz (R20) Measured by Oscillometry | Screening Visit, Day 1, Day 3, Day 7, Day 14, Day 28, Day 42 | Respiratory system resistance at an oscillation frequency of 20 Hz, measured by oscillometry during unforced tidal breathing. R20 predominantly reflects large/central airway resistance, as higher-frequency oscillations do not penetrate the peripheral airways. Values are reported as the mean of at least three technically acceptable measurements, performed according to the 2020 European Respiratory Society / American Thoracic Society technical standards for respiratory oscillometry. Unit of measure: cmH₂O·s/L. |
| Change from Baseline in Frequency Dependence of Resistance (R5-R20) Measured by Oscillometry | Screening Visit, Day 1, Day 3, Day 7, Day 14, Day 28, Day 42 | The difference between respiratory system resistance measured at 5 Hz and at 20 Hz (R5 minus R20), measured by oscillometry during unforced tidal breathing. R5-R20 is interpreted as an index of small airway dysfunction, with elevated values indicating heterogeneity of peripheral airway resistance. Values are calculated from the mean of at least three technically acceptable measurements at each frequency, performed according to the 2020 European Respiratory Society / American Thoracic Society technical standards for respiratory oscillometry. Unit of measure: cmH₂O·s/L. |
| Change from Baseline in Respiratory System Reactance at 5 Hz (X5) Measured by Oscillometry | Screening Visit, Day 1, Day 3, Day 7, Day 14, Day 28, Day 42 | Respiratory system reactance at an oscillation frequency of 5 Hz, measured by oscillometry during unforced tidal breathing. X5 represents the elastic and inertive properties of the respiratory system at low frequency and becomes more negative with increased peripheral airway obstruction or reduced lung compliance. Values are reported as the mean of at least three technically acceptable measurements, performed according to the 2020 European Respiratory Society / American Thoracic Society technical standards for respiratory oscillometry. Unit of measure: cmH₂O·s/L. |
| Change from Baseline in Area Under the Reactance Curve (AX) Measured by Oscillometry | Screening Visit, Day 1, Day 3, Day 7, Day 14, Day 28, Day 42 | The integrated area of the reactance curve from 5 Hz to the resonant frequency, measured by oscillometry during unforced tidal breathing. AX reflects the total elastic and inertive load of the respiratory system and is a sensitive composite index of peripheral airway dysfunction. Values are reported as the mean of at least three technically acceptable measurements, performed according to the 2020 European Respiratory Society / American Thoracic Society technical standards for respiratory oscillometry. Unit of measure: cmH₂O/L. |
| Change from Baseline in Resonant Frequency (Fres) Measured by Oscillometry | Screening Visit, Day 1, Day 3, Day 7, Day 14, Day 28, Day 42 | The oscillation frequency at which respiratory system reactance equals zero, measured by oscillometry during unforced tidal breathing. Fres represents the frequency at which the inertive and elastic forces of the respiratory system are equal in magnitude and opposite in direction; it shifts to higher frequencies with peripheral airway obstruction. Values are reported as the mean of at least three technically acceptable measurements, performed according to the 2020 European Respiratory Society / American Thoracic Society technical standards for respiratory oscillometry. Unit of measure: Hz. |
| Change from Baseline in Forced Expiratory Volume in 1 Second (FEV1) - Absolute Value | Screening Visit, and Days 7, 14, 28 and 42 | Forced expiratory volume in the first second of a maximal forced expiration following a full inspiration, measured by spirometry. FEV1 is a primary index of airflow obstruction. Values are reported as the highest acceptable value from at least three acceptable and two repeatable maneuvers, performed according to the 2019 European Respiratory Society / American Thoracic Society standards for spirometry. Unit of measure: liters. |
| Change from Baseline in Forced Expiratory Volume in 1 Second (FEV1) - Percent Predicted | Screening Visit, Day 7, Day 14, Day 28, Day 42 | Forced expiratory volume in the first second expressed as a percentage of the predicted value for the participant's age, sex, height, and ethnicity using the Global Lung Function Initiative (GLI-2012) reference equations. Measured by spirometry according to the 2019 European Respiratory Society / American Thoracic Society standards. Unit of measure: percent of predicted (%). |
| Change from Baseline in Forced Vital Capacity (FVC) - Absolute Value | Screening Visit, Day 7, Day 14, Day 28, Day 42 | Forced vital capacity, defined as the maximum volume of air exhaled with maximally forced effort from a position of maximal inspiration, measured by spirometry. Values are reported as the highest acceptable value from at least three acceptable and two repeatable maneuvers, performed according to the 2019 European Respiratory Society / American Thoracic Society standards for spirometry. Unit of measure: liters. |
| Change from Baseline in Forced Vital Capacity (FVC) - Percent Predicted | Screening Visit, Day 7, Day 14, Day 28, Day 42 | Forced vital capacity expressed as a percentage of the predicted value for the participant's age, sex, height, and ethnicity using the Global Lung Function Initiative (GLI-2012) reference equations. Measured by spirometry according to the 2019 European Respiratory Society / American Thoracic Society standards. Unit of measure: percent of predicted (%). |
| Change from Baseline in FEV1/FVC Ratio | Screening Visit, Day 7, Day 14, Day 28, Day 42 | The ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC), calculated from the highest acceptable FEV1 and FVC obtained during the same testing session. The FEV1/FVC ratio is the principal spirometric criterion used to identify airflow obstruction. Measured by spirometry according to the 2019 European Respiratory Society / American Thoracic Society standards. Unit of measure: ratio. |
| Change from Baseline in Peak Expiratory Flow (PEF) - Absolute Value | Screening Visit, Day 7, Day 14, Day 28, Day 42 | Peak expiratory flow, defined as the highest flow achieved during a maximally forced expiration starting from a position of maximal inspiration, measured by spirometry. Values are reported as the highest acceptable value from at least three acceptable and two repeatable maneuvers, performed according to the 2019 European Respiratory Society / American Thoracic Society standards for spirometry. Unit of measure: liters per minute (L/min). |
| Change from Baseline in Peak Expiratory Flow (PEF) - Percent Predicted | Screening Visit, Day 7, Day 14, Day 28, Day 42 | Peak expiratory flow expressed as a percentage of the predicted value for the participant's age, sex, height, and ethnicity using the Global Lung Function Initiative (GLI-2012) reference equations. Measured by spirometry according to the 2019 European Respiratory Society / American Thoracic Society standards. Unit of measure: percent of predicted (%). |
Countries
United Kingdom, United States
Contacts
CONTACTKaren Fusaro
Outcome results
None listed