Study Examining PrEP-001 in Subjects With Asthma

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II, Double-Blinded, Randomised, Controlled Study to Examine the Prophylactic Efficacy, Safety and Tolerability of PrEP-001 in Asthmatic Subjects Subsequently Challenged With Human Rhinovirus (HRV-16)

Conditions
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Asthma

Intervention / Treatment
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* Drug: PrEP-001
* Drug: G-004


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMP - PrEP-001<br>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) | Drug: PrEP-001<br>* A spray dried powder for intranasal administration formulated from an aqueous mixture of pre-gelatinized waxy maize starch and the drug substance delivered using a single dose nasal powder device.<br>|
| Placebo Comparator: Placebo - G-004<br>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). | Drug: G-004<br>* A spray dried pre-gelatinized waxy maize starch powder (G-001) in the single dose nasal powder device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Endpoint: The Area Under the Curve (AUC) of total symptom score post viral challenge. | 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. | Day -14 to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Efficacy Endpoint: Symptom Scores: Area Under the Curve (AUC) | 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. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Symptom Scores: Duration of symptoms | Time (days). | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Symptom Scores: Peak symptoms score | Numerical sum of all individual composite symptoms. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Symptom Scores: Time to peak symptoms | Time (days). | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Symptom Scores: Time to resolution from peak symptoms | Time (days). | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Incidence(s) of illness and infection: viral shedding | Number of subjects with viral shedding. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Incidence(s) of illness and infection: incidence of laboratory-confirmed Influenza illness | The number of subjects with laboratory-confirmed influenza infection. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Incidence(s) of illness and infection: laboratory confirmed Influenza A/Perth/16/2009 (H3N2) Virus infection | The number of subjects with laboratory-confirmed influenza A/Perth/16/2009 (H3N2) Virus infection. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Incidence(s) of illness and infection: HRV-like-illness | The number of subjects with HRV-like illness. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Sub-clinical infection | The number of subjects with Sub-clinical illness. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Upper respiratory tract illness | The number of subjects with Upper respiratory tract illness. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Lower respiratory tract illness | The number of subjects with Lower respiratory tract illness. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Febrile illness | The number of subjects with Febrile illness. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Systemic illness | The number of subjects with Systemic illness. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Non-sick and uninfected | The number of subjects Non-sick and uninfected. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Viral replication, as measured by tissue culture assay | The number of subjects with viral replication. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Seroconversion | The number of subjects with seroconversion. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Viral Load Parameters: Area under the curve (AUC) of viral load, as measured by nasopharyngeal swab RT-qPCR | Viral load data supplied in Log10 Copies/mL. These values used to calculate the Area Under the Curve (AUC) for each subject. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Duration of virus shedding, as measured by nasal wash RT-qPCR | Time (days). | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Peak virus shedding, as measured by nasal wash RT-qPCR | The highest observed RT-qPCR viral load value. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Viral Load Parameters: Time to peak viral shedding, as measured by nasal wash RT-qPCR | Time (days). | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Time to resolution from peak viral shedding, as measured by nasal wash RT-qPCR. | Time (days). | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Area under the curve (AUC) of viral load, as measured by nasal wash TCID50. | Tissue culture viral load data supplied in log10 TCID50/mL. These values used to calculate the Area Under the Curve (AUC) for each subject. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Duration of virus shedding, as measured by nasal wash TCID50. | Time (days). | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Peak virus shedding, as measured by nasal wash TCID50. | The highest observed RT-qPCR viral load value. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Time to peak viral shedding, as measured by nasal wash TCID50. | Time (days). | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Total weight of nasal discharge produced post Viral Challenge to Quarantine discharge. | Weight (grams). | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Change in lung function compared to pre-Challenge. | Peak Expiratory Flow (L/min) and FEV1 (L) | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Change in Asthma Control Questionnaire (ACQ) score compared to pre-Challenge. | ACQ score. | Day -4 to Day 28 | 
| Secondary Efficacy Endpoint: Change in Fractional exhaled nitric oxide (FeNO) compared to pre-Challenge. | FeNO (ppb). | Day -4 to Day 28 |