Clinical Trials Register

Summary
EudraCT Number:	2014-000091-25
Sponsor's Protocol Code Number:	2014GU001B
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:	2014-07-11
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

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2014-000091-25

A.3

Full title of the trial

A single-centre, placebo-controlled, double-blinded, randomized, cross-over study of Iloprost (Ventavis®) in patients with Eisenmenger syndrome

A.3.1

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

A single-centre, placebo-controlled, double-blinded, randomized, cross-over study of Iloprost (Ventavis®) in patients with Eisenmenger syndrome

A.3.2

Name or abbreviated title of the trial where available

Iloprost in patients with Eisenmenger Syndrome

A.4.1

Sponsor's protocol code number

2014GU001B

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	Royal Brompton and Harefield NHS Foundation Trust
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bayer PLC
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	Royal Brompton and Harefield NHS Foundation Trust
B.5.2	Functional name of contact point	Ira Jakupovic
B.5.3	Address:
B.5.3.1	Street Address	Royal Brompton Hospital, Research Office, Chelsea Wing, Level 2
B.5.3.2	Town/ city	Sydney Street
B.5.3.3	Post code	SW3 6NP
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	020 7351 8121
B.5.6	E-mail	i.jakupovic@rbht.nhs.uk

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	Yes
D.2.1.1.1	Trade name	Iloprost
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Pharma AG
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Ventavis
D.3.4	Pharmaceutical form	Inhalation solution
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	Iloprost
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	5 to 10
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Inhalation solution
D.8.4	Route of administration of the placebo	Inhalation use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Pulmonary Arterial Hypertension Eisenmenger syndrome

E.1.1.1

Medical condition in easily understood language

PAH Eisenmenger

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10037405
E.1.2	Term	Pulmonary hypertension primary
E.1.2	System Organ Class	100000004855

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10037406
E.1.2	Term	Pulmonary hypertension secondary
E.1.2	System Organ Class	100000004855

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the impact of iloprost - an inhaled pulmonary vasodilator (opens up the blood vessels in the lung)- on exercise capacity in patients with the congenital heart condition Eisenmenger Syndrome.

E.2.2

Secondary objectives of the trial

To assess the impact of iloprost on quality of life, oxygen levels in the blood (saturations), blood markers of “heart strain” (brain natriuretic peptide (bnp)) and heart function, as determined by an echocardiograph (ultrasound of the heart).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion criteria:
1. Patients > 18 years
2. Body weight > 40 kg
3. Functional class III (1998 WHO classification)
4. Patients with documented oxygen saturation < 90%, at rest or during exercise with room air
5. Patients with established pulmonary hypertension related to congenital heart disease and post – tricuspid lesion able to perform a 6-minute walk test with latest walking distance < 400m or deterioration of 30m within 1 Year on dual oral therapy or patient not tolerating oral therapy.
6. Patients stable for at least 3 months prior to screening.
7. Patients providing written informed consent

E.4

Principal exclusion criteria

Exclusion criteria:
1. Pregnant patients.
2. Trisomy 21
3. Obstructive lung disease (FEV1/FVC<60%).
4. Patients with systolic blood pressure <90 mm Hg.
5. Patients with other conditions that may affect the ability to perform a six minute walk test.
6. Patients unable to provide informed consent and comply with the protocol.
7. Patients with known coronary artery disease.
8. Patients who have started or stopped specific treatment for PAH within one month of screening, excluding anticoagulation.
9. Patients active on an organ transplant list.
10.Patients taking other investigational drugs/devices
11.Patients taking other Prostacyclin analogues, like Epoprostenol or Treprostinil.
12.Patients with planned surgical intervention during the study period.
13.Patients with HIV.

E.5 End points

E.5.1

Primary end point(s)

To assess the impact of Iloprost on exercise performance for a 6 Minute Walk Test (6MWT).

E.5.1.1

Timepoint(s) of evaluation of this end point

Once patients have consented to the study they will be admitted for 3 days/2 nights to titrate the drug or placebo up to the maximum dose. 12 weeks later they will then return for a further 2 days/1 night to stop the medication. 1-2 weeks later the patients will return to receive the opposite solution and will be monitored again for 3 days/2 night and at the end of the following 12 weeks stay for 2 days/1 night. There will be 4 time points during the study when the patient is monitored.

E.5.2

Secondary end point(s)

To assess the impact of Iloprost on haemodynamic parameters, echocardiographic parameters, serum neuropeptide levels, Quality of Life (QoL), oxygen saturation at rest and on WHO functional class

E.5.2.1

Timepoint(s) of evaluation of this end point

The participants will be evaluated at 4 time points whilst enrolled into the study.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

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

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1