Clinical Trials Register

Summary
EudraCT Number:	2012-001863-64
Sponsor's Protocol Code Number:	AP301-II-001
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-05-31
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

Austria - BASG

A.2

EudraCT number

2012-001863-64

A.3

Full title of the trial

Proof of concept study in male and female intensive care patients to investigate the clinical effect of repetitive orally inhaled doses of AP301 on alveolar liquid clearance in acute lung injury

A.3.1

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

Proof of concept study in male and female intensive care patients to investigate the clinical effect of repetitive orally inhaled doses of AP301 on alveolar liquid clearance in acute lung injury

A.4.1

Sponsor's protocol code number

AP301-II-001

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	Apeptico Forschung und Entwicklung GmbH
B.1.3.4	Country	Austria
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	Apeptico Forschung und Entwicklung GmbH
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Apeptico Forschung und Entwicklung GmbH
B.5.2	Functional name of contact point
B.5.3	Address:
B.5.3.1	Street Address	Mariahilfer Staße 136, Top 1.15
B.5.3.2	Town/ city	Wien
B.5.3.3	Post code	1150
B.5.3.4	Country	Austria
B.5.4	Telephone number	00436641432919
B.5.5	Fax number	0043125330337795
B.5.6	E-mail	b.fischer@apeptico.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	Yes
D.2.5.1	Orphan drug designation number	EU/3/09/677
D.3 Description of the IMP
D.3.1	Product name	AP301
D.3.4	Pharmaceutical form	Powder for nebuliser 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.3.9.1	CAS number	8000019-76-3
D.3.9.2	Current sponsor code	AP301
D.3.9.3	Other descriptive name	human tumour necrosis factor alpha-derived peptide Cys-Gly-Gln-Arg-Glu-Thr-Pro-Glu-Gly-Ala-Glu-Ala-Lys-Pro-Trp-Tyr-Cys
D.3.9.4	EV Substance Code	SUB14950MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
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	Nebuliser 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

Acute Pulmonary oedema

E.1.1.1

Medical condition in easily understood language

Acute Lung Injury

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

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 effect of orally inhaled AP301 on alveolar liquid clearance in ALI patients with the purpose to assess the treatment associated changes of extravascular lung water (EVLW) within 7 days of treatment.

E.2.2

Secondary objectives of the trial

To assess:
• the treatment associated changes of oxygenation as measured by the PaO2 / FiO2 ratio until day 7 of therapy,
• the ventilatory plateau pressure and other ventilation parameters (Tidal volume, positive endexpiratory pressure, PIP, FiO2, respiratory rate, mean airway pressure and peak airway pressure) until day 7 of therapy,
• the Murray lung injury score (a composite variable that includes components of oxygenation, compliance, positive end-expiratory pressure, and the appearance of the chest radiograph),
• the duration of stay at ICU in the first 28 days,
• the duration of controlled ventilation period until extubation,
• number of days free from ventilatory support [for > 48 h] in the first 28 days
• the survival status at day 28,
• the local and systemic safety and tolerability and to identify possible dose related adverse events.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- age ≥ 18
- intubated and mechanically ventilated male and female patients of the Intensive Care Units of the Department of Anesthesia, General Intensive Care and Pain Control
- meets the criteria of ALI (as defined by the American-European Consensus Conference on ALI/ ARDS):
- Onset of ALI within 48 hours
- Bilateral infiltrates seen on frontal chest radiograph
- PCWP ≤ 18 mm Hg or no clinical evidence of left atrial hypertension
- paO2/ FiO2 ratio ≤ 300 mm Hg

- EVLW in PiCCO® at screening ≥ 8 ml/PBW
- Meeting criteria for extensive hemodynamic monitoring according to investigators discretion
- Informed consent:
- For patients that are temporarily unable to consent (e.g. comatose patients) a subsequent informed consent has to be provided.

E.4

Principal exclusion criteria

Medical Issues
• History of clinically relevant allergies or idiosyncrasies to AP301 or any other inactive ingredient(s) of the investigational product
• Brainstem death at screening
• Current evidence of septic shock as defined by the Surviving Sepsis Campaign (Presence of acute organ dysfunction secondary to infection plus hypotension with systolic blood pressure < 90 mm Hg or mean arterial pressure (MAP) < 70 mm Hg for not less than one hour which cannot be reversed with fluid resuscitation)
• Neutrophil count <0.3 x 10^9 L
• Patients under immunosuppression: high dose steroids (> 80 mg Prednisolone /d; > 300 mg hydrocortisone / d), cancer treatment (chemotherapy or biological) or therapy with other immunosuppressive agents for organ transplantation within 2 weeks
• BMI < 18.5 or > 35
• Pregnancy / lactation or intention to fall pregnant during the time course of the study
• Women of childbearing potential who are not using adequate contraception

General Issues
• Participation in other interventional drug trials

E.5 End points

E.5.1

Primary end point(s)

Primary Endpoint is EVWL (measured with PiCCO® technique) between day 0 and day 7 of treatment.

E.5.1.1

Timepoint(s) of evaluation of this end point

from baseline to day 7

E.5.2

Secondary end point(s)

• Oxygenation index (PaO2 / FiO2 ratio) until day 7 of treatment
• Ventilator plateau pressure until day 7 of treatment
• Murray Lung Injury Score until day 7 of treatment
• Ventilation parameters / lung function: tidal volume (Vt), positive endexpiratory pressure (PEEP), PIP, respiratory rate, FiO2 , meak airway pressure, peak airway pressure until day 7 of treatment
• Duration of stay at ICU in the first 28 days
• Duration of controlled ventilation period until extubation
• Number of days free from ventilation support (for > 48 h) in the first 28 days
• Survival status at day 28
• the local and systemic safety and tolerability and to identify possible dose related adverse events

E.5.2.1

Timepoint(s) of evaluation of this end point

baseline to day 7 respectively day 28 (+7)

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

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

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

Yes

E.8.1.7.1

Other trial design description

stratified

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.8.4.1

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

Yes

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)

Yes

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Subjects are incapable of giving consent for reasons linked to their medical condition. They have Acute Lung Injury and are connected to a ventilator.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

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

2012-07-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-06-12

P. End of Trial
P.	End of Trial Status	Completed

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