Clinical Trials Register

Summary
EudraCT Number:	2016-004261-10
Sponsor's Protocol Code Number:	AR-105-002
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2017-03-28
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

Germany - PEI

A.2

EudraCT number

2016-004261-10

A.3

Full title of the trial

Placebo-controlled, double-blind, randomized study of Aerucin® as
adjunct therapy to antibiotics in the treatment of P. aeruginosa
pneumonia

A.3.1

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

Placebo-controlled, double-blind, randomized study of Aerucin® as
adjunct therapy to antibiotics in the treatment of P. aeruginosa
pneumonia

A.4.1

Sponsor's protocol code number

AR-105-002

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03027609

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	Aridis Pharmaceuticals, Inc.
B.1.3.4	Country	United States
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	Aridis Pharmaceuticals, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Aridis Pharmaceuticals, Inc.
B.5.2	Functional name of contact point	Clinical Group
B.5.3	Address:
B.5.3.1	Street Address	5941 Optical Court
B.5.3.2	Town/ city	San Jose
B.5.3.3	Post code	CA 95138
B.5.3.4	Country	United States
B.5.4	Telephone number	+1408385 1742
B.5.5	Fax number	+1408960 3822
B.5.6	E-mail	delamepa@aridispharma.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	Aerucin®
D.3.2	Product code	AR-105
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INN name not assigned yet
D.3.9.2	Current sponsor code	Aerucin®
D.3.9.3	Other descriptive name	AR-105, CM101, F429, aerubumab
D.3.9.4	EV Substance Code	SUB186715
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	27.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
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	Concentrate for solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

P. aeruginosa pneumonia

E.1.1.1

Medical condition in easily understood language

Pneumonia caused by bacteria P. aeruginosa

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	19.1
E.1.2	Level	PT
E.1.2	Classification code	10035664
E.1.2	Term	Pneumonia
E.1.2	System Organ Class	10021881 - Infections and infestations

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

1. To assess the efficacy of Aerucin®, administered as a single dose in addition to standard
antibiotic regimen, in terms of clinical cure at day 14, i.e., resolution of the P. aeruginosa
pneumonia event diagnosed at enrollment, as compared to standard antibiotic therapy alone.
2. To assess the clinical safety and tolerability of Aerucin® in the study population.

E.2.2

Secondary objectives of the trial

-Clinical Efficacy Objectives:
1.Clinical cure: Clinical cure rate at day 4,7,21,28,using the same criteria as for the
primary efficacy objective.Time to clinical cure
2.Mortality: All-cause mortality.Pneumonia-related mortality post-treatment as adjudicated
by an independent, blinded committee
3.Respiratory function assessment:Changes in PaO2/FiO2.Need for mechanical ventilator
support
4.Overall clinical status:Changes in SOFA score
5.Health economics and well-being:antibiotic utilization, duration of: stay in the ICU,hospitalization, mechanical ventilation,intubation
-Pharmacokinetics:PK Profile over the study follow-up period
-Safety Objectives:To assess the immunogenicity of Aerucin®
-Microbiological Efficacy Objectives
1.Eradication of index P.aeruginosa at 4,7,14, 21, 28 days post-treatment
2.Relapse defined as a reoccurrence of pneumonia due to P. aeruginosa within the 28-day follow-up period
3.Reduction in bacterial load related to the index P. aeruginosa

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written Informed Consent given by the patient or, if not possible, by a legally authorized representative and/or an independent physician as authorized by the competent ethics committee (EC) or independent review board (IRB) and local regulations.
2. Diagnosis of pneumonia based on the following criteria:
a. A sequence of at least 2 chest X-rays showing the presence of new or progressive infiltrate(s) suggestive of bacterial pneumonia or 1 definitive chest X-ray diagnostic of pneumonia
b. Hypoxemia based on at least one of the following criteria:
i. PaO2/FiO2 <250
ii. PaO2 <60 mmHg
c. At least one of the following signs:
i. Documented fever (e.g., body temperature greater than or equal to 38º Celsius).
ii. Hypothermia (e.g., core body temperature less than or equal to 35º Celsius).
iii. Total peripheral white blood cell (WBC) count greater than or equal to 10,000 cells/μL (or mm3).
iv. Leukopenia with total WBC less than or equal to 4,500 cells/μL (mm3).
v. Greater than 15 percent immature neutrophils (bands) noted on peripheral blood smear.
3. To be at least 18 years of age.
4. To be treated in an ICU at the time of enrollment.
5. Endotracheal tube in place (tracheostomy is allowed),
6. The patient is mechanically ventilated.
7. Documented pulmonary infection with P. aeruginosa obtained by BAL, mini-BAL, protected endotracheal tube aspiration (ETA). For the purpose of randomization, P. aeruginosa must be identified either by:
a. On the basis of available results from a culture positive by any method for P. aeruginosa of a sample obtained less than 72 hours prior to randomization. In such case, a fresh sample must be obtained prior to treatment initiation for standard microbial culture by the local laboratory (including organism identification, quantitative culture and susceptibility testing); the corresponding culture results are not required prior to randomization.
OR
b. On the basis of a rapid diagnostic test (see section 14.3 for allowed methods). In such case, the same sample must be used for standard microbial culture by the local laboratory (including organism identification, quantitative culture and susceptibility testing). The corresponding culture results are not required prior to randomization.
8. APACHE II score ≥ 10 and ≤ 35 within 24 hours of enrollment

E.4

Principal exclusion criteria

1. The subject is moribund.
2. Effective antibacterial drug therapy for the index pneumonia administered continuously for 48 hours or more prior to initiation of study treatment.
3. Plasmapheresis (ongoing or planned)
4. Immunocompromised and at risk of infection by opportunistic pathogens including, but not limited to the following:
a. HIV / AIDS who are not stable under medication and/or most recent CD4 <200
b. Expected neutropenia due to chemotherapy
c. Absolute neutrophil count less than 500/μL (mm3)
d. Heart or lung transplant recipient within the past 6 months
5. Known hereditary complement deficiency.
6. Liver function deficiency associated with chronic conditions (e.g., liver cirrhosis Child- Pugh C).
7. Pulmonary disease that precludes evaluation of a therapeutic response (such as lung cancer resulting in bronchial obstruction or on the same side as the pneumonia, active tuberculosis, cystic fibrosis, granulomatous disease, fungal pulmonary infection, lung abscess, pleural empyema or post obstructive pneumonia)
8. Administration of anti-infective monoclonal antibody within 3 months prior to enrollment.
9. Women of childbearing potential who are sexually active and have not been using a medically acceptable method contraception for at least 12 months and in whom a pregnancy test is either not available or positive at the time of enrollment. Women who are surgically sterile or sterile for any other reason are eligible provided medical evidence is provided and maintained in the study file. Women who are post-menopausal as evidenced by the absence of menstruation for at least 1 year are eligible; the date of the last menstruation is to be recorded in the study file unless postmenopausal status is obvious due to age.
10. Known lack of treatment compliance from prior studies or ongoing medical care based on medical records and Principal Investigator’s judgment and/or the capacity of the patient to comply with all study requirements.
11. Any medical, psychological, cognitive, social or legal conditions that would interfere in the ability to give an Informed Consent OR the absence of a legally valid representative of the patient or independent physician allowed and able to give consent on his/her behalf.
12. Participation as subject in another interventional study within 30 days prior to the first dose of study treatment, or planned participation in such a study during the study or within 30 days of its completion by the patient. Patients who participate in observational or epidemiological studies are eligible provided this does not interfere with their capacity or the capacity of the study staff to comply with all study requirements.

E.5 End points

E.5.1

Primary end point(s)

Clinical cure, relapse ( pneumonia due to P. aeruginosa), or reinfection (pneumonia due to a pathogen other than P. aeruginosa)

E.5.1.1

Timepoint(s) of evaluation of this end point

Clinical cure, i.e., resolution of the pneumonia event diagnosed at enrollment. “Clinical cure” is resolution of pneumonia as determined by an independent adjudication committee based on objective criteria. Clinical cure at day 14 will be used as primary clinical efficacy parameter.

E.5.2

Secondary end point(s)

Secondary Clinical Efficacy Parameters
1. Clinical cure:
- Clinical cure rate at day 4, 7, 21 and 28.
- Time to clinical cure.
2. Mortality:
- All-cause mortality
- Pneumonia-related mortality
- Time to death over the 28-day follow-up period.
3. Respiratory function assessment: PaO2/FiO2
4. Overall clinical status: SOFA
5. Health economics and well-being: antibiotic utilization, duration of stay in the ICU,
duration of hospitalization, ventilator-free days.
Microbiological Endpoints

E.5.2.1

Timepoint(s) of evaluation of this end point

The clinical course of pneumonia will be assessed daily by the investigator.
Secondary endpoints will be assessed for analytical purposes on day 4, 7, 14, 21 and 28.

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

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

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.8.2.4

Number of treatment arms in the trial

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

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

Belgium

Czech Republic

France

Germany

Greece

Hungary

Italy

Korea, Republic of

Poland

Russian Federation

Spain

Taiwan

United Kingdom

United States

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

LPLV

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.1.1.1

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

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

When patients are intubated and not able to provide consent, the consent or the approval will be provided according to the local law specific for the country (by LAR, court, independent physician etc).

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

108

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

2017-09-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-08-21

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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