NCT03027609

Adjunctive Therapeutic Treatment With Human Monoclonal Antibody AR-105 (Aerucin®) in P. Aeruginosa Pneumonia

Completed Phase 2 Results posted Last updated 17 March 2022

What this trial tests

Phase 2 trial testing AR-105 in Pseudomonas Aeruginosa Pneumonia in 158 participants. Completed in 25 April 2019.

Timeline

29 March 2017

Primary endpoint
25 April 2019

25 April 2019

Quick facts

Lead sponsor	Aridis Pharmaceuticals, Inc.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	158
Start date	29 March 2017
Primary completion	25 April 2019
Estimated completion	25 April 2019
Sites	111 locations across Georgia, France, Russia, Greece, Ukraine, Peru, Belgium, Taiwan

Drugs / interventions tested

• AR-105 — full drug profile →
• Placebo

Conditions studied

• Pseudomonas Aeruginosa Pneumonia — all drugs for Pseudomonas Aeruginosa Pneumonia →

Sponsor

Aridis Pharmaceuticals, Inc. — full company profile →

Who can join

18 and older, any sex, with Pseudomonas Aeruginosa Pneumonia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Clinical Cure on Day 21 Primary · 21 days following dosing

A summary of the number (%) of patients who were cured on or before Day 21 (micro-ITT population) is provided, by treatment group

Observed Cured

Group	Value	95% CI
AR-105	34
Control	37

Imputed Cured

Group	Value	95% CI
AR-105	6
Control	5

Not Cured

Group	Value	95% CI
AR-105	25
Control	20

Reinfection same pathogen

Group	Value	95% CI
AR-105	5
Control	2

New Infection Different Pathogen

Group	Value	95% CI
AR-105	0
Control	3

New infection Unknown pathogen

Group	Value	95% CI
AR-105	0
Control	0

Clinical Cure on Day 7 Secondary · 7 days following dosing

A summary of the number (%) of patients who were cured on or before Day 7 (micro-ITT population) is provided, by treatment group

Cured Observed

Group	Value	95% CI
AR-105	16
Control	18

Cured Imputed

Group	Value	95% CI
AR-105	0
Control	0

Not Cured

Group	Value	95% CI
AR-105	52
Control	47

Re-infection Same Pathogen

Group	Value	95% CI
AR-105	1
Control	0

New Infection Different Pathogen

Group	Value	95% CI
AR-105	1
Control	1

New Infection Unknown Pathogen

Group	Value	95% CI
AR-105	0
Control	1

Clinical Cure on Day 14 Secondary · 14 days following dosing

A summary of the number (%) of patients who were cured on or before Day 14 (micro-ITT population) is provided by treatment group

Observed Cured

Group	Value	95% CI
AR-105	36
Control	31

Imputed Cured

Group	Value	95% CI
AR-105	1
Control	2

Not Cured

Group	Value	95% CI
AR-105	29
Control	30

Reinfection same pathogen

Group	Value	95% CI
AR-105	1
Control	0

New Infection Different Pathogen

Group	Value	95% CI
AR-105	2
Control	4

New infection Unknown Pathogen

Group	Value	95% CI
AR-105	1
Control	0

Clinical Cure on Day 28 Secondary · 28 days following dosing

A summary of the number (%) of patients who were cured on or before Day 28 (micro-ITT population) is provided by treatment group

Observed Cured

Group	Value	95% CI
AR-105	35
Control	38

Imputed Cured

Group	Value	95% CI
AR-105	9
Control	6

Not Cured

Group	Value	95% CI
AR-105	23
Control	16

Reinfection same pathogen

Group	Value	95% CI
AR-105	3
Control	3

New Infection Different Pathogen

Group	Value	95% CI
AR-105	0
Control	4

New infection Unknown Pathogen

Group	Value	95% CI
AR-105	0
Control	0

Absolute Difference Clinical Cure at Day 14 and 21 for Study 1 Secondary · Up to Day 21

Difference in percentage of clinical cure rates between the two treatment groups

Cured Day 14

Group	Value	95% CI
Subset AR-105 Study1	6
Subset Placebo Study1	8

Cured Day 21

Group	Value	95% CI
Subset AR-105 Study1	7
Subset Placebo Study1	10

Absolute Difference Clinical Cure at Day 14 and 21 for Study 2 Secondary · Up to Day 21

Difference in percentage of clinical cure rates between the two treatment groups

Cured Day 14

Group	Value	95% CI
Subset AR-105 Study2	2
Subset Placebo Study2	2

Cured Day 21

Group	Value	95% CI
Subset AR-105 Study2	2
Subset Placebo Study2	3

Adverse events — posted to ClinicalTrials.gov

Time frame: 1 month: from administration day (Day 0) up to Day 28 (28 days after administration). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

AR-105

Serious: 36/79 (46%)

Deaths: 25/79

Control

Serious: 22/79 (28%)

Deaths: 13/79

Serious adverse events (58 terms)

Reaction	System	AR-105	Control
Multiple organ dysfunction syndrome	General disorders	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—
Septic shock	Infections and infestations	—	—
Brain herniation	Injury, poisoning and procedural complications	—	—
Cardiac failure acute	Cardiac disorders	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—
Brain oedema	Nervous system disorders	—	—
Pneumonia	Infections and infestations	—	—
Sepsis	Infections and infestations	—	—
Cardiac arrest	Cardiac disorders	—	—
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	—	—
Respiratory distress	Respiratory, thoracic and mediastinal disorders	—	—
Gastrointestinal haemorrhage	Gastrointestinal disorders	—	—
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	—	—
Abdominal abscess	Infections and infestations	—	—
Circulatory Collapse	Vascular disorders	—	—
Haemodynamic instability	Vascular disorders	—	—
Shock	Vascular disorders	—	—
Shock haemorrhagic	Vascular disorders	—	—
Cardiac death	General disorders	—	—
Systemic inflammatory response syndrome	General disorders	—	—
Gastrointestinal stoma complication	Injury, poisoning and procedural complications	—	—
Transaminases increased	Investigations	—	—
Acute left ventricular failure	Cardiac disorders	—	—
Acute myocardial infarction	Cardiac disorders	—	—

Other adverse events (33 terms — click to expand)

Reaction	System	AR-105	Control
Anaemia	Blood and lymphatic system disorders	—	—
Hypotension	Vascular disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—
Multiple organ dysfunction syndrome	General disorders	—	—
Decubitus ulcer	Skin and subcutaneous tissue disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Hyperkalaemia	Metabolism and nutrition disorders	—	—
Septic shock	Infections and infestations	—	—
Urinary tract infection	Infections and infestations	—	—
Pyrexia	General disorders	—	—
Hydrothorax	Respiratory, thoracic and mediastinal disorders	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—
Brain oedema	Nervous system disorders	—	—
Pneumonia	Infections and infestations	—	—
Sepsis	Infections and infestations	—	—
Oedema peripheral	General disorders	—	—
Agitation	Nervous system disorders	—	—
Bradycardia	Cardiac disorders	—	—
Pneumothorax	Respiratory, thoracic and mediastinal disorders	—	—
Tachypnoea	Respiratory, thoracic and mediastinal disorders	—	—
Delirium	Nervous system disorders	—	—
Insomnia	Nervous system disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Hypernatraemia	Metabolism and nutrition disorders	—	—
Hypovolaemia	Metabolism and nutrition disorders	—	—
Cystitis	Infections and infestations	—	—
Tracheobronchitis	Infections and infestations	—	—

Most-reported serious reactions: Multiple organ dysfunction syndrome, Respiratory failure, Septic shock, Brain herniation, Cardiac failure acute, Pulmonary embolism, Brain oedema, Pneumonia.

Data from ClinicalTrials.gov NCT03027609 adverse events section.

Sponsor's own description

Prospective, double-blind, randomized assessment of the efficacy, safety and pharmacokinetic of Aerucin® as adjunct treatment (in addition to standard of care antibiotics) for pneumonia caused by P. aeruginosa.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Virulence Factors of <i>Pseudomonas Aeruginosa</i> and Antivirulence Strategies to Combat Its Drug Resistance.
   Liao C, Huang X, Wang Q, Yao D, et al · · 2022 · cited 163× · PMID 35873152 · DOI 10.3389/fcimb.2022.926758
2. Fighting antibiotic resistance-strategies and (pre)clinical developments to find new antibacterials.
   Walesch S, Birkelbach J, Jézéquel G, Haeckl FPJ, et al · · 2023 · cited 102× · PMID 36533629 · DOI 10.15252/embr.202256033
3. Antimicrobial Resistance and Recent Alternatives to Antibiotics for the Control of Bacterial Pathogens with an Emphasis on Foodborne Pathogens.
   Helmy YA, Taha-Abdelaziz K, Hawwas HAE, Ghosh S, et al · · 2023 · cited 96× · PMID 36830185 · DOI 10.3390/antibiotics12020274
4. Therapies for multidrug resistant and extensively drug-resistant non-fermenting gram-negative bacteria causing nosocomial infections: a perilous journey toward 'molecularly targeted' therapy.
   El Chakhtoura NG, Saade E, Iovleva A, Yasmin M, et al · · 2018 · cited 60× · PMID 29310479 · DOI 10.1080/14787210.2018.1425139
5. Narrow-Spectrum Antibacterial Agents-Benefits and Challenges.
   Alm RA, Lahiri SD. · · 2020 · cited 48× · PMID 32708925 · DOI 10.3390/antibiotics9070418
6. How Three Self-Secreted Biofilm Exopolysaccharides of <i>Pseudomonas aeruginosa</i>, Psl, Pel, and Alginate, Can Each Be Exploited for Antibiotic Adjuvant Effects in Cystic Fibrosis Lung Infection.
   Chung J, Eisha S, Park S, Morris AJ, et al · · 2023 · cited 40× · PMID 37240055 · DOI 10.3390/ijms24108709
7. What Is New in the Anti-<i>Pseudomonas aeruginosa</i> Clinical Development Pipeline Since the 2017 WHO Alert?
   Reig S, Le Gouellec A, Bleves S. · · 2022 · cited 40× · PMID 35880080 · DOI 10.3389/fcimb.2022.909731
8. A New Take on an Old Remedy: Generating Antibodies against Multidrug-Resistant Gram-Negative Bacteria in a Postantibiotic World.
   Motley MP, Fries BC. · · 2017 · cited 35× · PMID 28989972 · DOI 10.1128/msphere.00397-17