Study Examining PrEP-001 in Subjects With Asthma

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)

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: PrEP-001; Drug: G-004

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IMP - 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)	Drug: PrEP-001; 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.
Placebo Comparator: Placebo - 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).	Drug: G-004; A spray dried pre-gelatinized waxy maize starch powder (G-001) in the single dose nasal powder device

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Efficacy Analysis: Proportion (on any occasion) of subjects with Grade 2 or worse symptoms at any day post-Viral Challenge.	Number of subjects with Grade 2 or higher symptoms at any day post-Viral Challenge.	Day -14 to Day 28
Exploratory Efficacy Analysis: Proportion of subjects with Grade 2 or worse symptoms at each day post-Viral Challenge.	Number of subjects with symptoms at Grade 2 or higher, at each day post-Viral Challenge.	Day -4 to Day 28
Exploratory Efficacy Analysis: Duration of Grade 2 or worse symptoms (post-Viral Challenge).	Time (days).	Day -4 to Day 28
Exploratory Efficacy Analysis: Proportion of subjects with any clinical symptoms (i.e., with Grade ≥ 1) (post-Viral Challenge).	The proportion of subjects with symptoms grade 1 or higher.	Day -4 to Day 28
Exploratory Efficacy Analysis: Proportion of subjects with Grade ≥1 symptom score for upper respiratory tract (URT) symptoms (post-Viral Challenge).	The proportion of subjects with upper respiratory tract symptoms.	Day -4 to Day 28
Exploratory Efficacy Analysis: Proportion of subjects with Grade ≥1 symptom score for lower respiratory tract (LRT) symptoms (post-Viral Challenge).	The proportion of subjects with lower respiratory tract symptoms.	Day -4 to Day 28
Exploratory Efficacy Analysis: Proportion of subjects with Grade ≥1 symptom score for systemic symptoms (post-Viral Challenge).	The proportion of subjects with systemic symptoms.	Day -4 to Day 28
Exploratory Efficacy Analysis: Time to peak for each reported and any symptoms (post-Viral Challenge).	Time (days).	Day -4 to Day 28
Exploratory Efficacy Analysis: Proportion of subjects with pyrexia.	The proportion of subjects with pyrexia.	Day -4 to Day 28
Exploratory Efficacy Analysis: Duration of pyrexia.	Time (hours).	Day -4 to Day 28
Exploratory Efficacy Analysis: Tympanic temperature.	Changes in tympanic temperature over time (post Viral Challenge) (degrees Celcius)	Day -4 to Day 28
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.	AUC of individual symptom scores.	Day -4 to Day 28
Exploratory Efficacy Analysis: Proportion of subjects with Lab-confirmed Clinical Symptoms of URTI.	The number of subjects with lab-confirmed clinical symptoms of URTI.	Day -4 to Day 28
Exploratory Efficacy Analysis: Proportion of subjects with Lab-confirmed Clinical Symptoms of LRTI.	The number of subjects with lab-confirmed clinical symptoms of LRTI.	Day -4 to Day 28
Exploratory Efficacy Analysis: Proportion of subjects with Lab-confirmed Clinical Symptoms of Systemic Illness (SI).	The number of subjects with lab-confirmed clinical symptoms of SI.	Day -4 to Day 28
Exploratory Efficacy Analysis: Overall total symptom score, Day 1 (assessment 1) to Day 8, using the 10-item symptom diary card.	Total symptom score.	Day -4 to Day 28
Exploratory Efficacy Analysis: Overall symptom scores (URT, LRT SVS), Day 1 (assessment 1) to Day 8, using the 10-item symptom diary card.	Total symptom score.	Day -4 to Day 28
Safety endpoint: Treatment-emergent Adverse Events (TEAE).	Incidence of treatment-emergent AEs (TEAE), overall, and by severity and causality (analysed descriptively).	Day -4 to Day 28
Safety endpoint: Clinical laboratory parameters.	Absolute values and change from baseline in routine clinical laboratory parameters by timepoint (analysed descriptively). Includes haematology, biochemistry, coagulation, cardiac enzymes, thyroid function tests and urinalysis parameters.	Day -4 to Day 28
Safety endpoint: Vital signs.	Absolute values and change from baseline in vital signs parameters by timepoint (analysed descriptively); systolic blood pressure (SBP) (mmHg), diastolic blood pressure (DBP) (mmHg), respiratory rate (RR) (breaths per minute), heart rate (HR) (beats per minute) and SpO2 (%).	Day -4 to Day 28
Safety endpoint: Physical Examination.	Physical examination findings (analysed descriptively).	Day -4 to Day 28
Safety endpoint: Spirometry.	Absolute and changes from baseline for FEV1 [absolute] (L), FEV1 [% predicted] (%), FVC [absolute] (L), FVC [% predicted] (%), FEV1/FVC ratio [absolute], FEV1/FVC ratio [% predicted] (%), maximum mid expiratory flow (MMEF) [absolute] (L/sec) and MMEF [% predicted]). The lung function parameter Peak Expiratory Flow [L/min] will also be summarised (analysed descriptively).	Day -4 to Day 28
Safety endpoint: ECGs.	12-lead electrocardiogram (ECG) findings (analysed descriptively).	Day -4 to Day 28
Safety endpoint: Asthma Exacerbations (Number)	Number and percentage of subjects experiencing any asthma exacerbations.	Day -4 to Day 28
Safety endpoint: Duration of each asthma exacerbation	Time (days)	Day -4 to Day 28
Safety endpoint: Time to first asthma exacerbation	Time (days)	Day -4 to Day 28
Safety endpoint: Subjects requiring treatment for asthma exacerbation	Number of subjects requiring oral or parenteral steroids as treatment for their exacerbation.	Day -4 to Day 28
Safety endpoint: Subjects requiring hospitalisation for asthma exacerbation	Number of subjects requiring hospitalisation for their exacerbation.	Day -4 to Day 28

Collaborators and Investigators

• Sponsor: Hvivo
• Collaborators: Prep Biopharm Limited

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2015
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: June 13, 2017
• First Submitted That Met QC Criteria: September 25, 2017
• First Posted (Actual): September 29, 2017

Study Record Updates

• Last Update Posted (Actual): September 29, 2017
• Last Update Submitted That Met QC Criteria: September 25, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: PrEP-CS-002