Study Examining PrEP-001 in Subjects With Asthma
- Registration Number
- NCT03296917
- Lead Sponsor
- Hvivo
- Brief Summary
Phase 2 study, to examine the prophylactic efficacy, safety and tolerability of PrEP-001 in asthmatics who have been infected with the human rhinovirus (HRV16) after receiving two doses of the study drug/placebo.
- Detailed Description
Screening took place up to 90 days before quarantine, where volunteers were asked to complete an informed consent and undergo scheduled screening assessments to determine their eligibility.
Eligible volunteers were invited to test and record their respiratory symptoms and peak expiratory flow (PEF), medications and any adverse events in diary cards from Day -14 to Day -5.
They attended Quarantine on Day -4/-3, received the study drug/placebo intra nasally on Day -2 and Day -1 and subsequently challenged with HRV16 on Day 0. Randomisation to receive study drug/placebo was 1:1.
Volunteers remained in the quarantine unit for 8 days after inoculation.
PEF self-testing continued from Day 9 to Day 28.
On Day 20 (±3 days) and Day 28 (±5 days), volunteers attended follow up visits where they were assessed by a study physician for well-being, on-going symptoms and adverse events.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
- Aged 18 to 55 years on the day of first dosing with IMP.
- Physician diagnosed asthma for at least 6 months prior to Screening and using treatment equivalent up to and including Global Initiative for Asthma (GINA) Stage 3.
- In good health with no history of major medical conditions (other than asthma) that will interfere with subject safety, as defined by medical history, physical examination, and routine laboratory tests as determined by the Investigator at a screening evaluation.
- Any ex-smoker or smoker with a history of more than 10 pack-years.
- History of life-threatening asthma, Diagnosis of COPD as defined by the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2014 guidelines.
- Any history or evidence of any clinically significant medical and psychiatric conditions
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IMP - PrEP-001 PrEP-001 In Viral Challenge arm cohort: A nasal dose of 6400 μg PrEP-001 equally divided over both nostrils on 2 consecutive days (Day -2 and Day -1). In the Safety arm's first dose cohort: A nasal dose of 6400 μg PrEP-001 equally divided over both nostrils on 2 consecutive days (Day -2 and Day -1). Then assuming no significant safety issues with the lower dose (as determined by blinded review by the DSMB team), the Safety arm's second dose cohort will consist of: A nasal dose of 12800 μg PrEP-001 equally divided over both nostrils on 2 consecutive days (Day -2 and Day -1) Placebo - G-004 G-004 In the Viral Challenge arm and each Safety Arm cohort: A nasal dose of placebo equally divided over both nostrils on 2 consecutive days (Day -2 and Day -1).
- Primary Outcome Measures
Name Time Method Primary Efficacy Endpoint: The Area Under the Curve (AUC) of total symptom score post viral challenge. Day -14 to Day 28 AUC of total symptom scores (upper respiratory tract (URT), lower respiratory tract (LRT) and systemic viral symptoms (SVS)). Total symptom scores (from the symptom diary card) used to calculate the AUC. The primary endpoint is only being derived from the Viral Challenge arm.
- Secondary Outcome Measures
Name Time Method Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Sub-clinical infection Day -4 to Day 28 The number of subjects with Sub-clinical illness.
Secondary Efficacy Endpoint: Symptom Scores: Area Under the Curve (AUC) Day -4 to Day 28 AUC of individual symptom scores (upper respiratory tract (URT), lower respiratory tract (LRT) and systemic viral symptoms (SVS)). A total symptom score is derived for each subject, separately for each assessment (symptom diary card) on each day.
Secondary Efficacy Endpoint: Symptom Scores: Duration of symptoms Day -4 to Day 28 Time (days).
Secondary Efficacy Endpoint: Symptom Scores: Peak symptoms score Day -4 to Day 28 Numerical sum of all individual composite symptoms.
Secondary Efficacy Endpoint: Symptom Scores: Time to peak symptoms Day -4 to Day 28 Time (days).
Secondary Efficacy Endpoint: Symptom Scores: Time to resolution from peak symptoms Day -4 to Day 28 Time (days).
Secondary Efficacy Endpoint: Incidence(s) of illness and infection: viral shedding Day -4 to Day 28 Number of subjects with viral shedding.
Secondary Efficacy Endpoint: Incidence(s) of illness and infection: incidence of laboratory-confirmed Influenza illness Day -4 to Day 28 The number of subjects with laboratory-confirmed influenza infection.
Secondary Efficacy Endpoint: Incidence(s) of illness and infection: laboratory confirmed Influenza A/Perth/16/2009 (H3N2) Virus infection Day -4 to Day 28 The number of subjects with laboratory-confirmed influenza A/Perth/16/2009 (H3N2) Virus infection.
Secondary Efficacy Endpoint: Incidence(s) of illness and infection: HRV-like-illness Day -4 to Day 28 The number of subjects with HRV-like illness.
Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Upper respiratory tract illness Day -4 to Day 28 The number of subjects with Upper respiratory tract illness.
Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Lower respiratory tract illness Day -4 to Day 28 The number of subjects with Lower respiratory tract illness.
Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Febrile illness Day -4 to Day 28 The number of subjects with Febrile illness.
Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Systemic illness Day -4 to Day 28 The number of subjects with Systemic illness.
Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Non-sick and uninfected Day -4 to Day 28 The number of subjects Non-sick and uninfected.
Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Viral replication, as measured by tissue culture assay Day -4 to Day 28 The number of subjects with viral replication.
Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Seroconversion Day -4 to Day 28 The number of subjects with seroconversion.
Secondary Efficacy Endpoint: Viral Load Parameters: Area under the curve (AUC) of viral load, as measured by nasopharyngeal swab RT-qPCR Day -4 to Day 28 Viral load data supplied in Log10 Copies/mL. These values used to calculate the Area Under the Curve (AUC) for each subject.
Secondary Efficacy Endpoint: Duration of virus shedding, as measured by nasal wash RT-qPCR Day -4 to Day 28 Time (days).
Secondary Efficacy Endpoint: Peak virus shedding, as measured by nasal wash RT-qPCR Day -4 to Day 28 The highest observed RT-qPCR viral load value.
Secondary Efficacy Endpoint: Viral Load Parameters: Time to peak viral shedding, as measured by nasal wash RT-qPCR Day -4 to Day 28 Time (days).
Secondary Efficacy Endpoint: Time to resolution from peak viral shedding, as measured by nasal wash RT-qPCR. Day -4 to Day 28 Time (days).
Secondary Efficacy Endpoint: Area under the curve (AUC) of viral load, as measured by nasal wash TCID50. Day -4 to Day 28 Tissue culture viral load data supplied in log10 TCID50/mL. These values used to calculate the Area Under the Curve (AUC) for each subject.
Secondary Efficacy Endpoint: Duration of virus shedding, as measured by nasal wash TCID50. Day -4 to Day 28 Time (days).
Secondary Efficacy Endpoint: Peak virus shedding, as measured by nasal wash TCID50. Day -4 to Day 28 The highest observed RT-qPCR viral load value.
Secondary Efficacy Endpoint: Time to peak viral shedding, as measured by nasal wash TCID50. Day -4 to Day 28 Time (days).
Secondary Efficacy Endpoint: Change in Asthma Control Questionnaire (ACQ) score compared to pre-Challenge. Day -4 to Day 28 ACQ score.
Secondary Efficacy Endpoint: Change in Fractional exhaled nitric oxide (FeNO) compared to pre-Challenge. Day -4 to Day 28 FeNO (ppb).
Secondary Efficacy Endpoint: Total weight of nasal discharge produced post Viral Challenge to Quarantine discharge. Day -4 to Day 28 Weight (grams).
Secondary Efficacy Endpoint: Change in lung function compared to pre-Challenge. Day -4 to Day 28 Peak Expiratory Flow (L/min) and FEV1 (L)