Clinical Trials Register

Summary
EudraCT Number:	2007-003621-24
Sponsor's Protocol Code Number:	MG-101-01
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2008-11-17
Trial 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

Italy - Italian Medicines Agency

A.2

EudraCT number

2007-003621-24

A.3

Full title of the trial

Double-blind, randomized, placebo-controlled, dose-finding, parallel-group study to assess the hemodynamic effects, clinical efficacy, tolerability and safety of Aviptadil (Vasoactive Intestinal Peptide) after single and repeated inhalation in patients with pulmonary arterial hypertension

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

MG-101-01

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	MONDOGEN AG
B.1.3.4	Country	Switzerland
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Yes
D.2.5.1	Orphan drug designation number	EU/3/03/173
D.3 Description of the IMP
D.3.1	Product name	Aviptadil
D.3.2	Product code	VIP
D.3.4	Pharmaceutical form	Nebuliser emulsion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Aviptadil
D.3.9.1	CAS number	40077-57-4
D.3.9.2	Current sponsor code	VIP
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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.IMP: 2
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/03/173
D.3 Description of the IMP
D.3.1	Product name	Aviptadil
D.3.2	Product code	VIP
D.3.4	Pharmaceutical form	Nebuliser emulsion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Aviptadil
D.3.9.1	CAS number	40077-57-4
D.3.9.2	Current sponsor code	VIP
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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.IMP: 3
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/03/173
D.3 Description of the IMP
D.3.1	Product name	Aviptadil
D.3.2	Product code	VIP
D.3.4	Pharmaceutical form	Nebuliser emulsion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Aviptadil
D.3.9.1	CAS number	40077-57-4
D.3.9.2	Current sponsor code	VIP
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	12.5
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Nebuliser emulsion
D.8.4	Route of administration of the placebo	Inhalation use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Nebuliser emulsion
D.8.4	Route of administration of the placebo	Inhalation use
D.8 Placebo: 3
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Nebuliser emulsion
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 (PAH) due to idiopathic pulmonary arterial hypertension (IPAH), familial PAH or PAH associated with connective tissue diseases (CTD) (e.g. systemic sclerosis, systemic lupus erythematosus) or to repaired congenital heart defects (RCHD).

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10065150
E.1.2	Term	Associated with pulmonary arterial hypertension

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10064911
E.1.2	Term	Pulmonary arterial hypertension

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10065151
E.1.2	Term	Idiopathic pulmonary arterial hypertension

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10065152
E.1.2	Term	Familial pulmonary arterial hypertension

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 efficacy of a number of doses of Aviptadil acutely and after 12 weeks of treatment

E.2.2

Secondary objectives of the trial

To assess the safety and tolerability of a number of doses of Aviptadil

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and female patients between 18 and 80 years of age with IPAH, familial PAH or PAH associated with CTD or RCHD. 2. Patients with New York Heart Association (NYHA) functional class II or III. 3. Patients who have received stablized therapy with the endothelin receptor antagonist bosentan or the phosphodiesterase type 5 inhibitor sildenafil or a combination of both for at least 1 month prior to screening. 4. Symptomatic PAH diagnosed as either IPAH, familial PAH or PAH associated with CTD or RCHD clinically stable for at least 1 month prior to the inclusion. 5. An unencouraged 6-MWT of more than 200 meters at screening. 6. Prior cardiac catheterization consistent with PAH, specifically mean pulmonary arterial pressure &#8805; 25 mmHg (at rest), pulmonary capillary wedge pressure (or left ventricular end diastolic pressure) &#8804; 15 mmHg and PVR > 3 mmHg/L/min. 7. Echocardiogram data acquired within 12 months prior to study drug administration that are consistent with PAH, specifically evidence of right ventricular hypertrophy or dilation, evidence of normal left ventricular function, and absence of mitral valve stenosis. 8. Chest radiograph or CT angiography consistent with the diagnosis of PAH generated within 12 months prior to study drug administration. 9. Able to understand and willing to sign the Informed Consent Form

E.4

Principal exclusion criteria

1. Patients with NYHA functional class I or IV. 2. Patients with PAH due to conditions other than IPAH, familial PAH or PAH associated with CTD or RCHD. 3. Patients who are on therapy with prostanoids, endothelin receptor antagonists other than bosentan, phosphodiesterase type 5 inhibitors other than sildenafil or calcium channel blockers. 4. Patients with Eisenmenger’s Syndrome (a condition where the patient has a septal defect of the heart or a persistent ductus arteriosus and where resulting pulmonary hypertension creates a reversal of the shunt). 5. Patients who have a new type of chronic therapy (e.g. a different category of vasodilator, diuretic) for PAH added within the last month, except anticoagulants. 6. Patients who have received therapy with an investigational drug within 1 month prior to the start of this study or who are scheduled to receive another investigational drug during the course of this study. 7. Patients who have discontinued regular medication or who have changed dose or class of any medication within the last week, except anticoagulants. 8. Patients with a concomitant disease that could interfere with their ability to perform the 6 MWT. 9. Patients with an acute concomitant disease that could potentially complicate the assessment of PAH disease severity or response to therapeutic intervention. 10. Patients with any illness other than PAH which might reduce life expectancy to less than 6 months. 11. Patients incapable or unwilling to sign the informed consent. 12. Patients pregnant and/or lactating. 13. Patients with any pre existing disease known to cause pulmonary hypertension unless listed in the inclusion criteria. The following pre existing diseases are exclusionary: obstructive lung disease, parasitic disease affecting the pulmonary system, sickle cell anemia, mitral valve stenosis and portal hypertension. 14. Patients with a history of drug and/or alcohol abuse, as defined by the Investigator. 15. Females who are pregnant or plan to become pregnant during the study and females who are not using a highly effective method of birth control (failure rate less than 1% per year).

E.5 End points

E.5.1

Primary end point(s)

1. Percentage change in pulmonary vascular resistance (PVR; peak PVR reduction compared to baseline PVR) after a single Aviptadil inhalation on Day 2, where baseline PVR is defined as the value measured when stability is reached after instrumentation of the patients and peak PVR is defined as the lowest value of PVR in post-baseline assessments (at 15, 30, 45, 60, 90, 120, 150 or 180 minutes).

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

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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

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

Yes

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

Yes

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

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

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

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	6
F.4.2	For a multinational trial
F.4.2.1	In the EEA	39
F.4.2.2	In the whole clinical trial	48

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

2008-07-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-06-24

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2010-08-04

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