Clinical Trials Register

Summary
EudraCT Number:	2018-000240-26
Sponsor's Protocol Code Number:	PC_ASP_002
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-10-16
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2018-000240-26

A.3

Full title of the trial

An open-label, pilot study to assess safety, tolerability, pharmacokinetics and effects of inhaled PC945 in the pre-emptive treatment of Aspergillus fumigatus colonisation in lung transplant recipients

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Study of Inhaled PC945 in Patients who have had a Lung Transplant which will Investigate the Safety of PC945, how the Body Affects the Drug and how the Drug Affects the Body

A.4.1

Sponsor's protocol code number

PC_ASP_002

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Pulmocide Ltd
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Pulmocide Ltd
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pulmocide Ltd
B.5.2	Functional name of contact point	Director of Clinical Development
B.5.3	Address:
B.5.3.1	Street Address	Office Suite 3.01, 44 Southampton Buildings
B.5.3.2	Town/ city	London
B.5.3.3	Post code	WC2A 1AP
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+447766250133
B.5.6	E-mail	Lindsey@pulmocide.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	PC945
D.3.4	Pharmaceutical form	Nebuliser suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.2	Current sponsor code	PC945
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4.0
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Pre-emptive treatment of Aspergillus fumigatus colonisation in lung transplant recipients

E.1.1.1

Medical condition in easily understood language

Treatment of a non-symptomatic fungal lung infection in patients who have had a lung transplant

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10059259
E.1.2	Term	Pulmonary aspergillosis
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

• To assess the safety and tolerability of PC945 in lung transplant recipients with A. fumigatus colonisation
• To ascertain derived systemic pharmacokinetic parameters of PC945 and the potential circulating metabolite(s), if detectable, following single and repeat doses of PC945

E.2.2

Secondary objectives of the trial

• To ascertain airway/lung concentrations of PC945 during and after treatment. Lung concentrations of oral azoles will also be measured, if prescribed as SoC
• To investigate the effect of PC945 on eradication of A. fumigatus from BAL
• To investigate the effect of PC945 on the A. fumigatus fungal burden in BAL
• To investigate the effect of PC945 on markers of fungal infection in BAL
• To compare the tolerability and subject experience of inhaled amphotericin B (used as prophylaxis) and inhaled PC945 (used as pre-emptive treatment)
• To assess the safety and tolerability of an additional 8 weeks of PC945 treatment in lung transplant recipients with persistent A. fumigatus colonisation following the initial 28 days of PC945 treatment
• To measure the effect on lung function (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC])

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Surveillance Phase:
1. Between the ages of 18 and 85 years.
2. Received a single or bilateral lung transplant.
3. Provided written informed consent prior to transplant.

Pre-emptive treatment phase:
1. A positive test for A. fumigatus in BAL during the Surveillance Phase of the study
2. Provided written informed consent for participating in the Pre-Emptive Treatment Phase.

Follow-up Phase:
1. Subject is not eligible to receive pre-emptive PC945 treatment due to either clinical, endobronchial and/or radiological features of fungal disease OR a fungal infection other than A. fumigatus in BAL, that requires SoC antifungal treatment to be started during the Surveillance Phase of the study.
2. Provided written informed consent for participating in the follow-up phase for SoC antifungal treatment.

E.4

Principal exclusion criteria

Surveillance Phase:

1. Is precluded from participating in this study as a result of treatment with another investigational drug or participation in another clinical trial.
2. If female, the subject is pregnant, lactating or breast feeding.
3. Any other clinically significant disease or condition, which in the Investigator’s medical opinion would preclude the subject’s participation in a clinical trial (e.g., recent myocardial infarction).
4. Is employed or is a first-degree relative of anyone employed by Pulmocide, a participating clinical trial site, or any contract research organisation involved in the study.
5. Is receiving antiretroviral protease inhibitor therapy.
6. Has human immunodeficiency virus or chronic, active hepatitis infection, or had a positive hepatitis B surface antigen or hepatitis C virus RNA test prior to transplant.
7. Any known history or current evidence of alcohol or drug abuse that, in the Investigator’s opinion, would exclude the subject from participation in the study.

Pre-emptive Treatment Phase:
1. Clinical, endobronchial and/or radiological features of fungal disease.
2. Any other disease or condition, which in the Investigator’s medical opinion would preclude the subject’s participation in the Pre-Emptive Treatment Phase of the study (e.g., recent myocardial infarction).

Follow-up Phase:
1. Any other disease or condition, which in the Investigator’s medical opinion would preclude the subject’s participation in the follow-up phase for SoC antifungal treatment.

E.5 End points

E.5.1

Primary end point(s)

• Safety parameters:
o Adverse events
o 12-lead electrocardiogram (ECG) including QT interval corrected for Bazett’s formula (QTcB), QT interval, QRS interval, PR interval and ventricular rate
o Vital signs (systolic and diastolic blood pressure, pulse rate [supine], respiratory rate and oxygen saturation)
o Clinical laboratory evaluations (haematology, clinical chemistry and urinalysis); immunosuppressant levels
o Spirometry

• Derived pharmacokinetic parameters for systemic PC945 and the potential circulating metabolite(s), if detectable, including area under the concentration-time curve from 0 to 4 hours post-dose (AUC0-4h), maximum observed concentration (Cmax), concentration at the end of the dosage interval (Ctrough), time to maximum observed concentration (Tmax) and metabolite(s) to parent AUC ratio following single and repeat dosing

E.5.1.1

Timepoint(s) of evaluation of this end point

AEs: 48 h post-transplant until subject's last study-related procedure

ECG: Surveillance phase (SP) - Day (D) 1 and standard of care (SOC) bronchoscopy visits (BV); Pre-emptive treatment phase (PETP): Pre-dose (PD), Wk 2, 4, 16, start of extended treatment (ET), Wk 4, 8, 10 of ET and BV during ET; Follow-up phase (FUP): SOC BV

Vitals: SP: D1, SOC BV; PETP: PD, D1, Wk2, 4, 6, 16, start of ET, Wk 4, 8, 10 of ET and BV during ET; FUP: SOC BV

Labs: SP: D1; PETP: PD, Wk2, 4, 6, 16, start of ET, Wk 4, 8, 10 of ET and BV during ET; FUP: SOC BV

Spirometry: SP: D1, SOC BV; PETP: PD, D1, Wk2, 4, 6, 16, start of ET, Wk 4, 8, 10 of ET and BV during ET; FUP: SOC BV

PK: PETP: PD, D1 (0, 0.25, 0.5, 1, 2, 4 h), Wk2, 4 (0, 4 h), 6, 16, start of ET, Wk 4, 8, 10 of ET and BV during ET;

E.5.2

Secondary end point(s)

• Lung concentrations of PC945. These will be measured in BAL and/or in endobronchial brushings or biopsy (if collected as SoC) during and post-PC945 treatment. Calculation of lung:plasma ratio of PC945 concentrations, corrected for procedure-related dilution where appropriate. Concentrations of oral azoles given as SoC may also be measured.
• Results of markers of fungal infection at baseline, during and post pre-emptive PC945 treatment:
In BAL:
o Presence or absence of A. fumigatus on fungal culture
o A. fumigatus concentration measured by quantitative polymerase chain reaction (qPCR)
o The number of A. fumigatus colony forming units (CFU) on fungal culture
o Galactomannan levels
o Presence or absence of Aspergillus on an Aspergillus immunochromatographic lateral flow device (AspLFD)
o Presence or absence of fungal hyphae or pseudohyphae on cytological examination (if performed as standard of care)

•Tolerability and subject experience of inhaled PC945

• Tolerability and subject experience of inhaled amphotericin B

• Lung function parameters at baseline, during treatment and post pre-emptive PC945 treatment: FEV1 and FVC

E.5.2.1

Timepoint(s) of evaluation of this end point

Bronchoscopy: Surveillance phase (SP) - standard of care (SOC) bronchoscopy visits (BV); Pre-emptive treatment phase (PETP): Wk 2, 6, Wk 10 of extended treatment (ET) and BV during ET; Follow-up phase (FUP): SOC BV

Questionnaires: SP: SOC BV; PETP: PD, D1, Wk2, 4, 6, 16, start of ET, Wk 4, 8, 10 of ET and BV during ET; FUP: SOC BV

Spirometry: SP: D1, SOC BV; PETP: PD, D1, Wk2, 4, 6, 16, start of ET, Wk 4, 8, 10 of ET and BV during ET; FUP: SOC BV

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

none

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-11-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-05-17

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2020-06-01

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials