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Clinical Trial Results:
A phase IIa, randomised, double-blind, placebo-controlled study using outpatient setting to investigate the duration of effect and evaluate further safety of PrEP-001 given prophylactically in healthy subjects, subsequently challenged with human rhinovirus (HRV-16)

Summary
EudraCT number	2015-005492-25
Trial protocol	GB
Global end of trial date	07 Oct 2016

Results information
Results version number	v1(current)
This version publication date	21 Apr 2018
First version publication date	21 Apr 2018
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

PrEP-CS-003

ISRCTN number

US NCT number

NCT03338556

WHO universal trial number (UTN)

Sponsor organisation name

PrEP Biopharm Limited

Sponsor organisation address

42 New Road, London, United Kingdom, E1 2AX

Public contact

Bruce Malcolm Chief Scientific Officer, PrEP Biopharm Limited, info@prepbiopharm.com

Scientific contact

Bruce Malcolm Chief Scientific Officer, PrEP Biopharm Limited, info@prepbiopharm.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

07 Oct 2016

Is this the analysis of the primary completion data?

Yes

Primary completion date

07 Oct 2016

Global end of trial reached?

Yes

Global end of trial date

07 Oct 2016

Was the trial ended prematurely?

Main objective of the trial

To assess the prophylactic effect of repeated intranasal dosing of PrEP-001 in healthy subjects, subsequently challenged with HRV-16, on the changes in clinical symptoms when compared to placebo at two different dosing regimens

Protection of trial subjects

This trial was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the International Conference on Harmonisation (ICH) guidelines for Good Clinical Practice (GCP) and applicable regulatory requirements.

Background therapy

None

Evidence for comparator

Placebo

Actual start date of recruitment

30 Mar 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 102

Worldwide total number of subjects

102

EEA total number of subjects

102

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

102

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

All subjects recruited in the United Kingdom were healthy males and/or females, 18 to 55 years of age, who met the eligibility criteria. First patient consented 30 March 2016. Last Patient Last Visit 7 October 2016.

Screening details

Healthy males and/or females, 18 to 55 years, with no history of major medical conditions from the medical history, physical examination, and routine laboratory tests as determined by the Investigator at a screening evaluation.

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst

Blinding implementation details

Double blind

Are arms mutually exclusive

Yes

Cohort A - PrEP-001

Arm description

PrEP-001 6400 μg/day, equally divided over both nostrils, on 2 consecutive days. Dosed Day - 7 and Day - 6 prior to intranasal challenge with HRV-16 (Day 0).

Arm type

Experimental

Investigational medicinal product name

PrEP-001

Investigational medicinal product code

Other name

Pharmaceutical forms

Nasal powder

Routes of administration

Nasal use

Dosage and administration details

6.4 mg PrEP-001 nasal powder once daily

Cohort A - Placebo

Arm description

Placebo matching PrEP-001, equally divided over both nostrils, on 2 consecutive days. Dosed Day - 7 and Day - 6 prior to intranasal challenge with HRV-16 (Day 0).

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Nasal powder

Routes of administration

Nasal use

Dosage and administration details

6.4 mg matching placebo nasal powder once daily

Cohort B- PrEP-001

Arm description

PrEP-001 6400 μg/day, equally divided over both nostrils, on 2 consecutive days. Dosed Day - 4 and Day - 3 prior to intranasal challenge with HRV-16 (Day 0).

Arm type

Experimental

Investigational medicinal product name

PrEP-001

Investigational medicinal product code

Other name

Pharmaceutical forms

Nasal powder

Routes of administration

Nasal use

Dosage and administration details

6.4 mg PrEP-001 nasal powder once daily

Cohort B - Placebo

Arm description

Placebo matching PrEP-001, equally divided over both nostrils, on 2 consecutive days. Dosed Day - 4 and Day - 3 prior to intranasal challenge with HRV-16 (Day 0).

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Nasal powder

Routes of administration

Nasal use

Dosage and administration details

6.4 mg matching placebo nasal powder once daily

Number of subjects in period 1	Cohort A - PrEP-001	Cohort A - Placebo	Cohort B- PrEP-001	Cohort B - Placebo
Started	25	27	24	26
Completed	25	27	24	26

Baseline characteristics

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Reporting group title

Cohort A - PrEP-001

Reporting group description

PrEP-001 6400 μg/day, equally divided over both nostrils, on 2 consecutive days. Dosed Day - 7 and Day - 6 prior to intranasal challenge with HRV-16 (Day 0).

Reporting group title

Cohort A - Placebo

Reporting group description

Placebo matching PrEP-001, equally divided over both nostrils, on 2 consecutive days. Dosed Day - 7 and Day - 6 prior to intranasal challenge with HRV-16 (Day 0).

Reporting group title

Cohort B- PrEP-001

Reporting group description

PrEP-001 6400 μg/day, equally divided over both nostrils, on 2 consecutive days. Dosed Day - 4 and Day - 3 prior to intranasal challenge with HRV-16 (Day 0).

Reporting group title

Cohort B - Placebo

Reporting group description

Placebo matching PrEP-001, equally divided over both nostrils, on 2 consecutive days. Dosed Day - 4 and Day - 3 prior to intranasal challenge with HRV-16 (Day 0).

Reporting group values	Cohort A - PrEP-001	Cohort A - Placebo	Cohort B- PrEP-001	Cohort B - Placebo	Total
Number of subjects	25	27	24	26	102
Age categorical
Units: Subjects
Adults (18-55 years)	25	27	24	26	102
Age continuous
Units: years
arithmetic mean (standard deviation)	24.3 ± 6.26	24.9 ± 8.30	21.7 ± 2.93	22.2 ± 3.58	-
Gender categorical
Units: Subjects
Female	12	11	4	9	36
Male	13	16	20	17	66

End points

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Reporting group title

Cohort A - PrEP-001

Reporting group description

PrEP-001 6400 μg/day, equally divided over both nostrils, on 2 consecutive days. Dosed Day - 7 and Day - 6 prior to intranasal challenge with HRV-16 (Day 0).

Reporting group title

Cohort A - Placebo

Reporting group description

Placebo matching PrEP-001, equally divided over both nostrils, on 2 consecutive days. Dosed Day - 7 and Day - 6 prior to intranasal challenge with HRV-16 (Day 0).

Reporting group title

Cohort B- PrEP-001

Reporting group description

PrEP-001 6400 μg/day, equally divided over both nostrils, on 2 consecutive days. Dosed Day - 4 and Day - 3 prior to intranasal challenge with HRV-16 (Day 0).

Reporting group title

Cohort B - Placebo

Reporting group description

Placebo matching PrEP-001, equally divided over both nostrils, on 2 consecutive days. Dosed Day - 4 and Day - 3 prior to intranasal challenge with HRV-16 (Day 0).

Primary: Overall total symptom score, defined as the sum of the total symptom scores from Day 1 to Day 8, inclusive, using the 10-point symptom diary card

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End point title

Overall total symptom score, defined as the sum of the total symptom scores from Day 1 to Day 8, inclusive, using the 10-point symptom diary card

End point description

End point type

Primary

End point timeframe

Day 1 to Day 8

End point values	Cohort A - PrEP-001	Cohort A - Placebo	Cohort B- PrEP-001	Cohort B - Placebo
Number of subjects analysed	23	23	21	24
Units: Overall total symptom score
arithmetic mean (standard deviation)	22.5 ± 21.63	34.2 ± 38.67	36.2 ± 38.19	33.5 ± 40.54

ITT analysis set

Comparison groups

Cohort B- PrEP-001 v Cohort B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.519

Method

t-test, 2-sided

Confidence interval

Secondary: The area under the curve (AUC) of symptom scores, using symptoms from Day 1 to Day 8 from the 10-point symptom diary card, calculated separately for total symptoms, upper respiratory tract, lower respiratory tract and systemic viral symptoms

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End point title

The area under the curve (AUC) of symptom scores, using symptoms from Day 1 to Day 8 from the 10-point symptom diary card, calculated separately for total symptoms, upper respiratory tract, lower respiratory tract and systemic viral symptoms

End point description

Using 10 item diary card

End point type

Secondary

End point timeframe

Day 1 to Day 8

End point values	Cohort A - PrEP-001	Cohort A - Placebo	Cohort B- PrEP-001	Cohort B - Placebo
Number of subjects analysed	23	23	20	23
Units: AUC total symptom score
arithmetic mean (standard deviation)	10668.8 ± 10359.03	16543.3 ± 18742.21	17782.2 ± 18533.03	16385.7 ± 19936.53

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Reporting from consent to last patient last visit

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

19.0

Reporting group title

Cohort A - PrEP-001

Reporting group description

PrEP-001 6400 μg/day, equally divided over both nostrils, on 2 consecutive days. Dosed Day - 7 and Day - 6 prior to intranasal challenge with HRV-16 (Day 0).

Reporting group title

Cohort A - Placebo

Reporting group description

Placebo matching PrEP-001, equally divided over both nostrils, on 2 consecutive days. Dosed Day - 7 and Day - 6 prior to intranasal challenge with HRV-16 (Day 0).

Reporting group title

Cohort B- PrEP-001

Reporting group description

PrEP-001 6400 μg/day, equally divided over both nostrils, on 2 consecutive days. Dosed Day - 4 and Day - 3 prior to intranasal challenge with HRV-16 (Day 0).

Reporting group title

Cohort B - Placebo

Reporting group description

Placebo matching PrEP-001, equally divided over both nostrils, on 2 consecutive days. Dosed Day - 4 and Day - 3 prior to intranasal challenge with HRV-16 (Day 0).

Serious adverse events	Cohort A - PrEP-001	Cohort A - Placebo	Cohort B- PrEP-001	Cohort B - Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 25 (0.00%)	0 / 27 (0.00%)	0 / 24 (0.00%)	0 / 26 (0.00%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Cohort A - PrEP-001	Cohort A - Placebo	Cohort B- PrEP-001	Cohort B - Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	19 / 25 (76.00%)	16 / 27 (59.26%)	18 / 24 (75.00%)	11 / 26 (42.31%)
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 25 (0.00%)	0 / 27 (0.00%)	3 / 24 (12.50%)	1 / 26 (3.85%)
occurrences all number	0	0	3	2
Aspartate aminotransferase increased
subjects affected / exposed	0 / 25 (0.00%)	1 / 27 (3.70%)	2 / 24 (8.33%)	0 / 26 (0.00%)
occurrences all number	0	1	2	0
Blood fibrinogen increased
subjects affected / exposed	3 / 25 (12.00%)	2 / 27 (7.41%)	0 / 24 (0.00%)	0 / 26 (0.00%)
occurrences all number	3	2	0	0
C-reactive protein increased
subjects affected / exposed	0 / 25 (0.00%)	2 / 27 (7.41%)	2 / 24 (8.33%)	4 / 26 (15.38%)
occurrences all number	0	2	2	4
Lymphocyte count decreased
subjects affected / exposed	0 / 25 (0.00%)	2 / 27 (7.41%)	0 / 24 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	2	0	0
Blood bilirubin increased
subjects affected / exposed	1 / 25 (4.00%)	0 / 27 (0.00%)	1 / 24 (4.17%)	1 / 26 (3.85%)
occurrences all number	1	0	1	1
Neutrophil count decreased
subjects affected / exposed	1 / 25 (4.00%)	0 / 27 (0.00%)	1 / 24 (4.17%)	0 / 26 (0.00%)
occurrences all number	1	0	1	0
Injury, poisoning and procedural complications
injury, poisoning and procedural complications
subjects affected / exposed	12 / 25 (48.00%)	10 / 27 (37.04%)	8 / 24 (33.33%)	6 / 26 (23.08%)
occurrences all number	20	15	12	13
Sun burn
subjects affected / exposed	0 / 25 (0.00%)	1 / 27 (3.70%)	1 / 24 (4.17%)	0 / 26 (0.00%)
occurrences all number	0	1	1	0
Nervous system disorders
Headache
subjects affected / exposed	0 / 25 (0.00%)	0 / 27 (0.00%)	2 / 24 (8.33%)	0 / 26 (0.00%)
occurrences all number	0	0	3	0
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	0 / 25 (0.00%)	0 / 27 (0.00%)	1 / 24 (4.17%)	1 / 26 (3.85%)
occurrences all number	0	0	1	1
Respiratory, thoracic and mediastinal disorders
Epistaxis
subjects affected / exposed	3 / 25 (12.00%)	0 / 27 (0.00%)	0 / 24 (0.00%)	0 / 26 (0.00%)
occurrences all number	3	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

18 Mar 2016

Change of PI Change of Sponsor Representative Exclusion criteria added: o Subjects with a diagnosis of mild or moderate depressive episode(s) which occurred 2 or more years ago, with good evidence of preceding stressors and which resolved within approximately 3 months could be included in the Investigator's opinion – clarification of existing criteria o During screening, if subjects had a total cholesterol level > 6mmol/L they were excluded from the study- additional safety Minor administrative changes for clarity and aid clinical delivery 

14 Jun 2016

Change of design for Cohort C from day -13/14 dosing to Day -7 dosing only Change in primary endpoint from the area under the curve (AUC) of total symptom score to overall symptom score Amendment and additional secondary endpoints added Minor administrative changes to improve clarity and aid clinical delivery.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

The above study results support a daily dosing regime for PrEP-001.

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Clinical trials

Clinical Trial Results:
A phase IIa, randomised, double-blind, placebo-controlled study using outpatient setting to investigate the duration of effect and evaluate further safety of PrEP-001 given prophylactically in healthy subjects, subsequently challenged with human rhinovirus (HRV-16)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Overall total symptom score, defined as the sum of the total symptom scores from Day 1 to Day 8, inclusive, using the 10-point symptom diary card

Primary: Overall total symptom score, defined as the sum of the total symptom scores from Day 1 to Day 8, inclusive, using the 10-point symptom diary card

Secondary: The area under the curve (AUC) of symptom scores, using symptoms from Day 1 to Day 8 from the 10-point symptom diary card, calculated separately for total symptoms, upper respiratory tract, lower respiratory tract and systemic viral symptoms

Secondary: The area under the curve (AUC) of symptom scores, using symptoms from Day 1 to Day 8 from the 10-point symptom diary card, calculated separately for total symptoms, upper respiratory tract, lower respiratory tract and systemic viral symptoms

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A phase IIa, randomised, double-blind, placebo-controlled study using outpatient setting to investigate the duration of effect and evaluate further safety of PrEP-001 given prophylactically in healthy subjects, subsequently challenged with human rhinovirus (HRV-16)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Overall total symptom score, defined as the sum of the total symptom scores from Day 1 to Day 8, inclusive, using the 10-point symptom diary card

Primary: Overall total symptom score, defined as the sum of the total symptom scores from Day 1 to Day 8, inclusive, using the 10-point symptom diary card

Secondary: The area under the curve (AUC) of symptom scores, using symptoms from Day 1 to Day 8 from the 10-point symptom diary card, calculated separately for total symptoms, upper respiratory tract, lower respiratory tract and systemic viral symptoms

Secondary: The area under the curve (AUC) of symptom scores, using symptoms from Day 1 to Day 8 from the 10-point symptom diary card, calculated separately for total symptoms, upper respiratory tract, lower respiratory tract and systemic viral symptoms

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A phase IIa, randomised, double-blind, placebo-controlled study using outpatient setting to investigate the duration of effect and evaluate further safety of PrEP-001 given prophylactically in healthy subjects, subsequently challenged with human rhinovirus (HRV-16)