Placebo-controlled, double-blind, randomized study of Aerucin® asadjunct therapy to antibiotics in the treatment of P. aeruginosapneumonia

Phase 1

Conditions: Pseudomonas aeruginosa pneumonia
MedDRA version: 20.0Level: PTClassification code 10035664Term: PneumoniaSystem Organ Class: 10021881 - Infections and infestations
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2016-004261-10-BE

Lead Sponsor: Aridis Pharmaceuticals, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 154

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. To be at least 18 years of age.
3. To be treated in an ICU at the time of enrollment.
4. Endotracheal tube in place (tracheostomy is allowed).
5. The patient is mechanically ventilated.
6. Diagnosis of pneumonia based on the following criteria (a, b, and c, all must be met):
a. One definitive chest X-ray diagnostic of pneumonia, or a sequence of at least 2 chest X-rays showing the presence of new or progressive infiltrate(s) suggestive of bacterial pneumonia.
b. Hypoxemia based on at least one of the following measurements/criteria:
i. PaO2/FiO2 <250 mmHg (at sea level or equivalent for significant elevations above sea level) while intubated and mechanically ventilated, as one or more measures within ii. PaO2 <60 mmHg (at sea level or equivalent for significant elevations above sea level) while intubated and mechanically ventilated, as one or more measures within iii. Respiratory failure necessitating intubation and mechanical ventilation. If tracheostomy is in place, the need for mechanical ventilation.
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.
7. Documented pulmonary infection with P. aeruginosa obtained by BAL, mini-BAL, protected endotracheal tube aspiration (ETA) (collectively 'airway specimen'). For the study randomization, P. aeruginosa must be identified by one of the three methods below:
a. An airway specimen culture positive by any method for P. aeruginosa of specimen obtained less than 72 hours prior to randomization. A fresh airway specimen must be obtained prior to treatment initiation for baseline standard microbial culture by the local laboratory (including organism identification, quantitative/semi-quantitative culture and susceptibility testing); the corresponding culture results are not required prior to randomization.
OR
b. A rapid diagnostic test. In such case, the same sample must ALSO be used for standard microbial culture by the local laboratory (including organism identification, quantitative/semi-quantitative culture and susceptibility testing). The corresponding culture results are NOT required prior to randomization.
OR
c. A positive airway specimen culture by any method of P. aeruginosa from a specimen obtained at screening (quantitative, semi-quantitative).
8. APACHE II score = 10 and = 35 within 24 hours once subject has consented.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 54

Exclusion Criteria

1. The subject is moribund. Clinical judgment by the investigator that the subject is unlikely to survive the current illness/ICU-admission/treatment period despite delivery of adequate antibiotics for treatment of P.aeruginosa pneumonia.
2. Effective antibacterial drug therapy for the index pneumonia administered continuously for 48 hours or more prior to initiation of study treatment. Effective antibiotics would include those typically used to treat P. aeruginosa.
3. Plasmapheresis (ongoing or planned) or any procedure that would remove/filter out the monoclonal antibody/study drug.
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 dysfunction with a Child Pugh C score (Child Pugh score of A or B are acceptable at discretion of the PI).
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. Patient has received IV immunoglobulin therapy within 3 months prior to the Screening Visit.
9. Any woman of child-bearing potential (WOCBP) who does not have a negative pregnancy test result at Screening using SERUM or URINE testing based on Beta-subunit human chorionic gonadotropin (HCG) standard tests and methods from the local laboratory. Non-pregnant and non-lactating with confirmation via local laboratory testing is required. Woman who are post-menopausal as evidenced by the absence of menstruation for at least 1 year are eligible; the date of last menstruation is to be recorded in the study files unless post-menopausal status is obvious due to age.
10. Any sexually active subject who is unwilling to use acceptable methods of contraception for 120 days after dosing. WOCBP must agree to use an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, barrier methods, abstinence) or male partner sterilization alone for the duration of the study and for at least 120 days after dosing. Males with female partners of reproductive potential must agree to practice abstinence or to use a condom (male) plus an additional barrier method (female partner) of contraception for the duration of the study and for at least 120 days after dosing.
11. 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.
12. 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.
13. Participation as a 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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