Study Evaluating Safety, Tolerability, and Efficacy of Intravenous AP-SA02 in Subjects With S. Aureus Bacteremia

Study Overview
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Brief Summary
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Phase 1b/2a, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Escalation Study of the Safety, Tolerability, and Efficacy of Intravenous AP SA02 as an Adjunct to Best Available Antibiotic Therapy Compared to Best Available Antibiotic Therapy Alone for the Treatment of Adults With Bacteremia Due to Staphylococcus aureus

Detailed Description
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This study will be conducted in two phases: Phase 1b will to evaluate the safety and tolerability of multiple ascending intravenous (IV) doses of AP-SA02 or placebo as an adjunct to best available therapy (BAT) compared to BAT alone in subjects with SA bacteremia (SAB). Phase 2a will evaluate the efficacy, safety, and tolerability of multiple doses of AP-SA02 or placebo as an adjunct to BAT compared to BAT alone in subjects with complicated SAB.

Official Title
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Phase 1b/2a, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study of Safety, Tolerability, and Efficacy of Intravenous AP-SA02 as an Adjunct to Best Available Antibiotic Therapy for the Treatment of Adults With Bacteremia Due to Staphylococcus Aureus

Conditions
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Bacteremia, Staphylococcus Aureus, Staphylococcus Aureus Bacteremia, Bacteremia Staph, Bacteremia Due to Staphylococcus Aureus

Intervention / Treatment
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* Biological: AP-SA02
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: A hospitalized female or male ≥ 18 years old Positive blood culture for Staphylococcus aureus (SA) Source of SA infection controlled, or a plan for source control, if relevant Not pregnant or breastfeeding and is not of reproductive potential or agrees to use contraception if or reproductive potential Key Exclusion Criteria: Concomitant growth of organisms besides SA Left-sided infectious endocarditis by modified Duke criteria Known or suspected brain abscess or meningitis Known allergy to phage products

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AP-SA02<br>Anti-staphylococcal bacteriophage | Biological: AP-SA02<br>* Bacteriophage administered via intravenous bolus infusion<br>|
| Placebo Comparator: Placebo<br>Inactive isotonic solution | Other: Placebo<br>* Inactive Placebo administered via intravenous bolus infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-emergent Adverse Events (Safety and Tolerability) of multiple doses of intravenous AP-SA02 | Incidence and severity of treatment-emergent adverse events as assessed by CTCAE v4.0 | Day 1 first dose through Day 12 or through End of Study for serious AEs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Improvement or Response at Day 12 | Description of clinical outcome in the Microbiological Intent-to-Treat (mITT) Population. Clinical outcome of improvement or response is defined as survival with resolution of S. aureus-related clinical signs and symptoms as well as eradication of S. aureus bacteremia, and without new foci of infection or complications of S. aureus bacteremia | Day 12 | 
| Clinical Improvement or Response at 7 days after completion of antibiotic therapy | Description of clinical outcome in the Microbiological Intent-to-Treat (mITT) Population. Clinical outcome of improvement or response is defined as survival with resolution of S. aureus-related clinical signs and symptoms as well as eradication of S. aureus bacteremia, and without new foci of infection or complications of S. aureus bacteremia | 7 days post completion of best available antibiotic therapy | 
| Clinical Improvement or Response at End of Study | Description of clinical outcome in the Microbiological Intent-to-Treat (mITT) Population. Clinical outcome of improvement or response is defined as survival with resolution of S. aureus-related clinical signs and symptoms as well as eradication of S. aureus bacteremia, and without new foci of infection or complications of S. aureus bacteremia | 28 days post completion of best available antibiotic therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bacteriophage, Phage, Bacteremia, Staphylococcus Aureus, Staphylococcus, SAB