Study Drug Indication:
* Treatment of HRV infections in patients with COPD
Study Rationale:
An effective, easily administered therapy for RV infection would have the potential to reduce the serious health effects in vulnerable populations, such as those with COPD. Treatment of RV infection could reduce the severity and frequency of acute COPD exacerbations, preserve pulmonary function, prevent secondary bacterial infections, and mitigate the need for costly medical interventions, including inhaled agents, steroids, antibacterial drugs, emergency treatment, hospitalization, and mechanical ventilation. Thus, early treatment of acute COPD exacerbations related to RV infection could potentially improve both the quality of life and longevity of COPD patients.
Altesa BioSciences, Inc. is developing drugs to treat RV and other respiratory virus infections. VPV has been shown to inhibit RV in vitro and in human clinical trials. Furthermore, VPV has been administered to more than 650 study participants and has been well-tolerated. Based on its potential to prevent severe respiratory complications, Altesa BioSciences, Inc is continuing the development of this drug for the treatment of RV infection.
Study Dose justification:
* In patients with asthma, vapendavir doses of 264 mg bid and 528 mg bid were utilized and demonstrated reduced viral load and was well tolerated.
* A PK study established the pharmacokinetics of a free based micronized tablet in achieving adequate plasma levels after a single dose in fed adults.
Study Treatment Duration:
* 7 days
End of Study:
* Up to 63 days, including the screening and follow-up periods.
Study Centers:
* There will be 1 study centre, ICRRU within Imperial College Healthcare NHS site at St Mary's Hospital London, United Kingdom.
Study Treatment:
* 1:1 randomization to Vapendavir 500mg bid or placebo
Study Procedures:
* Screening period (Pregnancy test for females, Lung function tests (FEV1, FVC, PEF), Height and Weight/BMI Calculation, Physical Examination, Vital Signs, Medical and Surgical history, Blood sample, COPD assessment test)
* Baseline visit to clinic (Pregnancy test for females, Physical examination, Safety assessments, Vital Signs, Concomitant medication assessment, Nasal lavage/nasosorption, Chest X-Ray, ECG, Blood for hematology, biochemistry and liver function tests, Induced Sputum, Lung Function Tests (FEV1, FVC, PEF))
* Clinical Visit Day 1 (Randomization to treatment, Dispense Medication, Physical Examination, Safety Assessments, Vital Signs, Concomitant medication assessment, Nasal lavage/nasosorption, Chest X-Ray, ECG, Blood for hematology, biochemistry and liver function tests, Induced Sputum, Lung Function Tests (FEV1, FVC, PEF), Intranasal RV-A16 challenge)
* Treatment Commencement-Clinical Visit Days 1-28 (Physical Exam, Safety Assessments, Vital Signs, Concomitant Medication and food assessments, Diaries and eCRF completion, Treatment twice daily (If required), Drug Compliance, Nasal Lavage/nasosorption, Blood serum for biomarkers, Blood for hematology and biochemistry, Blood for PK, Pregnancy test for females, Lung Function Tests (FEV1, FVC, PEF))
* Treatment Commencement-Clinical Visit Day 42 (Physical Examination, Safety Assessments, Vital Signs, Concomitant medication and food assessments, Diaries and eCRF completion, Nasal lavage/nasosorption, Blood serum for biomarkers, blood for hematology, biochemistry and liver function tests, Blood sample taken to assess RV-A16 sero-positivity, Pregnancy test for females, Lung Function Tests (FEV1, FVC, PEF))
* Early Termination Visit (Physical Examination, Safety Assessments, Vital Signs, Concomitant medication and food assessments, Diaries and eCRF completion, Nasal lavage/nasosorption, Blood Serum for Biomarkers, Blood for hematology and biochemistry, Blood for PK, Sputum
* Unscheduled Visit (Physical Examination, Safety Assessments, Vital Signs, Concomitant medication and food assessments, Diaries and eCRF completion, Drug complicance, Lung function tests (FEV1, FVC, PEPF), Blood or PK-morning (or sampling))
* Study drug administered as soon as possible after onset of symptoms and documentation of HRV infection, but no greater than 48 hours after symptom onset.
Study Sample Size:
• 50 participants randomization will be 1:1 VPV : placebo. Participants will undergo 7 days of twice daily treatment. Treatment will commence after symptom onset or when the participant determines they have a clinical cold.
Statistical Methods:
* Efficacy Analysis: All participants infected and treated will comprise the infected and evaluable population and be included in the efficacy analysis (primary, secondary, exploratory endpoints). Subjects inoculated but not successfully infected will not be included in this analysis.
* Safety Analysis: All participants that have undergone any treatment with VPV or placebo will comprise the safety population and will be included in the safety analysis. Subjects that are inoculated, treated but not successfully infected will be included in this population.
* Inoculated \& Followed-Up Population: Participants that are inoculated, but that do not fit the criteria to undergo treatment or become pregnant will be followed up until Day 42 ± 2. This group will be composed of both uninfected and successfully infected participants and follow up will be to obtain data on the RV challenge model, COPD related symptoms and also for safety reasons.
* Statistical Analysis Plan: A comprehensive Statistical Analysis Plan (SAP) will be finalized prior to reporting of the study results. The SAP may modify the plans outlined in the protocol; however, any major modifications of planned analyses will be reflected in a protocol amendment.
