Clinical trial NCT03296917: Study Examining PrEP-001 in Subjects With Asthma
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Hvivo
Sponsor class: INDUSTRY
Collaborators: name: Prep Biopharm Limited
First posted: 2017-09-29
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Primary Efficacy Endpoint: The Area Under the Curve (AUC) of total symptom score post viral challenge.
timeFrame: Day -14 to Day 28
Secondary outcomes:
measure: Secondary Efficacy Endpoint: Symptom Scores: Area Under the Curve (AUC)
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Symptom Scores: Duration of symptoms
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Symptom Scores: Peak symptoms score
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Symptom Scores: Time to peak symptoms
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Symptom Scores: Time to resolution from peak symptoms
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: viral shedding
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: incidence of laboratory-confirmed Influenza illness
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: laboratory confirmed Influenza A/Perth/16/2009 (H3N2) Virus infection
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: HRV-like-illness
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Sub-clinical infection
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Upper respiratory tract illness
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Lower respiratory tract illness
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Febrile illness
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Systemic illness
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Non-sick and uninfected
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Viral replication, as measured by tissue culture assay
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Incidence(s) of illness and infection: Seroconversion
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Viral Load Parameters: Area under the curve (AUC) of viral load, as measured by nasopharyngeal swab RT-qPCR
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Duration of virus shedding, as measured by nasal wash RT-qPCR
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Peak virus shedding, as measured by nasal wash RT-qPCR
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Viral Load Parameters: Time to peak viral shedding, as measured by nasal wash RT-qPCR
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Time to resolution from peak viral shedding, as measured by nasal wash RT-qPCR.
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Area under the curve (AUC) of viral load, as measured by nasal wash TCID50.
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Duration of virus shedding, as measured by nasal wash TCID50.
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Peak virus shedding, as measured by nasal wash TCID50.
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Time to peak viral shedding, as measured by nasal wash TCID50.
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Total weight of nasal discharge produced post Viral Challenge to Quarantine discharge.
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Change in lung function compared to pre-Challenge.
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Change in Asthma Control Questionnaire (ACQ) score compared to pre-Challenge.
timeFrame: Day -4 to Day 28
measure: Secondary Efficacy Endpoint: Change in Fractional exhaled nitric oxide (FeNO) compared to pre-Challenge.
timeFrame: Day -4 to Day 28
Other outcomes:
measure: Exploratory Efficacy Analysis: Proportion (on any occasion) of subjects with Grade 2 or worse symptoms at any day post-Viral Challenge.
timeFrame: Day -14 to Day 28
measure: Exploratory Efficacy Analysis: Proportion of subjects with Grade 2 or worse symptoms at each day post-Viral Challenge.
timeFrame: Day -4 to Day 28
measure: Exploratory Efficacy Analysis: Duration of Grade 2 or worse symptoms (post-Viral Challenge).
timeFrame: Day -4 to Day 28
measure: Exploratory Efficacy Analysis: Proportion of subjects with any clinical symptoms (i.e., with Grade ≥ 1) (post-Viral Challenge).
timeFrame: Day -4 to Day 28
measure: Exploratory Efficacy Analysis: Proportion of subjects with Grade ≥1 symptom score for upper respiratory tract (URT) symptoms (post-Viral Challenge).
timeFrame: Day -4 to Day 28
measure: Exploratory Efficacy Analysis: Proportion of subjects with Grade ≥1 symptom score for lower respiratory tract (LRT) symptoms (post-Viral Challenge).
timeFrame: Day -4 to Day 28
measure: Exploratory Efficacy Analysis: Proportion of subjects with Grade ≥1 symptom score for systemic symptoms (post-Viral Challenge).
timeFrame: Day -4 to Day 28
measure: Exploratory Efficacy Analysis: Time to peak for each reported and any symptoms (post-Viral Challenge).
timeFrame: Day -4 to Day 28
measure: Exploratory Efficacy Analysis: Proportion of subjects with pyrexia.
timeFrame: Day -4 to Day 28
measure: Exploratory Efficacy Analysis: Duration of pyrexia.
timeFrame: Day -4 to Day 28
measure: Exploratory Efficacy Analysis: Tympanic temperature.
timeFrame: Day -4 to Day 28
measure: Exploratory Efficacy Analysis: Area under the curve (AUC) of symptom scores using the 13-item symptom diary card (total, URT, LRT and SVS), Day 1 (assessment 1) to Day 8.
timeFrame: Day -4 to Day 28
measure: Exploratory Efficacy Analysis: Proportion of subjects with Lab-confirmed Clinical Symptoms of URTI.
timeFrame: Day -4 to Day 28
measure: Exploratory Efficacy Analysis: Proportion of subjects with Lab-confirmed Clinical Symptoms of LRTI.
timeFrame: Day -4 to Day 28
measure: Exploratory Efficacy Analysis: Proportion of subjects with Lab-confirmed Clinical Symptoms of Systemic Illness (SI).
timeFrame: Day -4 to Day 28
measure: Exploratory Efficacy Analysis: Overall total symptom score, Day 1 (assessment 1) to Day 8, using the 10-item symptom diary card.
timeFrame: Day -4 to Day 28
measure: Exploratory Efficacy Analysis: Overall symptom scores (URT, LRT SVS), Day 1 (assessment 1) to Day 8, using the 10-item symptom diary card.
timeFrame: Day -4 to Day 28
measure: Safety endpoint: Treatment-emergent Adverse Events (TEAE).
timeFrame: Day -4 to Day 28
measure: Safety endpoint: Clinical laboratory parameters.
timeFrame: Day -4 to Day 28
measure: Safety endpoint: Vital signs.
timeFrame: Day -4 to Day 28
measure: Safety endpoint: Physical Examination.
timeFrame: Day -4 to Day 28
measure: Safety endpoint: Spirometry.
timeFrame: Day -4 to Day 28
measure: Safety endpoint: ECGs.
timeFrame: Day -4 to Day 28
measure: Safety endpoint: Asthma Exacerbations (Number)
timeFrame: Day -4 to Day 28
measure: Safety endpoint: Duration of each asthma exacerbation
timeFrame: Day -4 to Day 28
measure: Safety endpoint: Time to first asthma exacerbation
timeFrame: Day -4 to Day 28
measure: Safety endpoint: Subjects requiring treatment for asthma exacerbation
timeFrame: Day -4 to Day 28
measure: Safety endpoint: Subjects requiring hospitalisation for asthma exacerbation
timeFrame: Day -4 to Day 28
Locations:
Study officials:
affiliation: Sponsor's Representative
name: John Efthimiou
role: STUDY_CHAIR
References: