Safety & Efficacy of an Antibacterial Protein Molecule Applied Topically to the Nostrils of Volunteers and Patients

A Randomized Double-Blind Placebo-Controlled Study to Determine Safety of P128 Applied to Nares of Healthy Volunteers and Safety And Efficacy of Any Patient Including Chronic Kidney Disease Patients Who Are Nasal Carriers of S.Aureus.

The purpose of this study is to determine whether the antibacterial protein P128 is (i) safe and well tolerated in healthy volunteers and in chronic kidney diseases patients on dialysis, (ii) is it effective in reducing the nasal carriage of pathogen (Staphylococcus aureus) in humans.

Study Overview

• Status: Completed
• Conditions: Bacterial Infections; Infectious Disease
• Intervention / Treatment: Drug: P128-0.1 mg; Drug: P128-0.3 mg; Drug: P128-1.0 mg; Drug: Placebo

Detailed Description

Staphylococcus aureus with acquired multiple-drug resistance poses an increasing problem in both hospital and community settings. S. aureus is known to cause infections ranging in severity from skin infection to systemic bacteremia. As nasal colonization is the principal ecological niche for these bacteria and has been shown to be a significant risk factor in developing S. aureus infection, it is of importance to develop an efficient therapy that is able to clear this bacterium from human nostrils.

In-vivo studies have shown that P128 treatment is efficacious in reducing and decolonizing MRSA bacteria from rat nostrils.

Pre-clinical safety studies in animal models indicated no test drug related toxicity signs at the site of application or systemically.

The present clinical trial is conducted in four parts. Part A consists of safety and tolerability studies in 4 cohorts of 3 healthy subjects who are administered a single dose of three escalating concentrations of the drug and placebo intra-nasally. Part B consists of safety & tolerability as in part A but with multiple doses (3 doses/day for 5 days). Part C comprises of safety/tolerability as well as efficacy studies in chronic kidney disease patients stable on dialysis who are nasal carriers of S.aureus or MRSA on a treatment regimen as in Part B. Part D comprises of safety and efficacy studies in any patient who are nasal carriers of S.aureus or MRSA with single dose of 3 escalating concentrations of the drug and placebo intra-nasally.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore
    • National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy human volunteer
• Any patient clinically stable who are nasal carrier of S. aureus or MRSA including Chronic Kidney disease patients stable on dialysis

Exclusion Criteria:

• Presence of active systemic bacterial infection of any nature not cured at least 4 weeks before enrollment.
• Systemic or intra-nasal anti-bacterial treatment during four week period before enrollment
• Pregnancy, breast feeding during the study duration
• Participation in any other intervention study during the past three months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: P128-0.1 mg; Three healthy adult volunteers will be enrolled to P128-0.1 mg single dose-cohort 1 (Part A) Three healthy adult volunteers will be enrolled to P128-0.1 mg multiple doses-Cohort 4 (Part B) Ten chronic kidney disease patients will be enrolled to P128-0.1 mg multiple doses (Part C) Ten patient harboring S.aureus nasally will be enrolled to P128-0.1 mg single dose (Part D)	Drug: P128-0.1 mg; P-128 at 0.1 mg divided evenly between the nares is administered once in Part A; multiple times in Part B and Part C; and once in Part D.; Other Names: Single dose in Part A; Multiple doses in Part B; Multiple doses in Part C; Single dose in Part D
EXPERIMENTAL: P128-0.3 mg; Three healthy adult volunteers will be enrolled to P128-0.3 mg single dose-Cohort 2 (Part A) Three healthy adult volunteers will be enrolled to P128-0.3 mg multiple doses-Cohort 5 (Part B) Ten chronic kidney disease patients will be enrolled to P128-0.3 mg multiple doses (Part C) Ten patient harboring S.aureus nasally will be enrolled to P128-0.3 mg single dose (Part D)	Drug: P128-0.3 mg; P-128 at 0.3 mg divided evenly between the nares is administered once in Part A; multiple times in Part B and Part C; and once in Part D.; Other Names: Single dose in Part A; Multiple doses in Part B; Multiple doses in Part C; Single dose in Part D
EXPERIMENTAL: P128-1.0 mg; Three healthy adult volunteers will be enrolled to P128-1.0 mg single dose-Cohort 3 (Part A) Three healthy adult volunteers will be enrolled to P128-1.0 mg multiple doses-Cohort 6 (Part B) Ten chronic kidney disease patients will be enrolled to P128 1.0 mg multiple doses (Part C) Ten patient harboring S.aureus nasally will be enrolled to P128-1.0 mg single dose (Part D)	Drug: P128-1.0 mg; P-128 at 1.0 mg divided evenly between the nares is administered once in Part A; multiple times in Part B and Part C; once in Part D.; Other Names: Single dose in Part A; Multiple doses in Part B; Multiple doses in Part C; Single dose in Part D
PLACEBO_COMPARATOR: Placebo; Three healthy adult volunteers will be enrolled to placebo single dose-Cohort 1-3 (Part A) Three healthy adult volunteers will be enrolled to placebo multiple doses-Cohort 4-6 (Part B) Ten chronic kidney disease patients will be enrolled to placebo multiple doses (Part C) Ten patient harboring S.aureus nasally will be enrolled to placebo single dose (Part D)	Drug: Placebo; Placebo was administered to both nares once in part A, multiple times in Part B and Part C, Once in part D; Other Names: Single dose in Part A; Multiple doses in Part B; Multiple doses in Part C; Single dose in Part D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability (Part A, Part B, Part C and Part D); Efficacy (Part C and Part D)	The number of adverse events, type of adverse events, frequency of adverse events and proportion of subjects with adverse events and the severity, seriousness and the relationship of adverse event to the treatment. For efficacy, rate of S. aureus clearance following 5 days of treatment with various doses of P128 for Part C; rate of clearance following single dose treatment with various doses of P128 for Part D.	30 Days (Part A and Part B), 20 Days (Part C), 7 Days (Part D)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity (Part A, Part B and Part C)	Levels of antibodies to the investigational product in serum before and after administration of the drug will be compared to understand immunogenicity of the drug.	8 Days (Part A), 13 Days (Part B)
Pharmacokinetics (Part A and Part B)	AUC0-t, AUC0-∞, Cmax, Tmax, Tlag, Kel and AUC_% will be measured; AUC means area under curve Part A Baseline Pre-dose: before 1st dose on Day 1. Post - dose: 5 min, 15 min, 30 min, 1hr, 2hrs and 6hrs after first dose(on day 1) Part B Baseline Pre-dose: before 1st dose on Day 1. Post - dose: 5 min, 15 min, 30 min, 1hr, 2hrs and 6hrs after first dose(on day 1) Pre-final dose Post - dose: 5 min, 15 min, 30 min, 1 hr, and 12 hours post last dose - after the last dose is administered.	1 Day (Part A), 6 days (Part B)
Secondary efficacy (Part C)	Rate of S. aureus clearance following 3 days of treatment with various doses of P128	3 days
Re-colonization (Part C)	Rate of re-colonization by S. aureus 7 and 14 days after the last day of treatment with various doses of P128	14 Days

Collaborators and Investigators

• Sponsor: GangaGen, Inc.
• Investigators: Principal Investigator: Dale A Fisher, MBBS, FRACP, National University Hospital, Singapore; Study Director: Surinder Kher, MD, Manipal Acunova Ltd, Bangalore

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (ACTUAL): October 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: December 5, 2012
• First Submitted That Met QC Criteria: December 8, 2012
• First Posted (ESTIMATE): December 11, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): March 7, 2016
• Last Update Submitted That Met QC Criteria: March 4, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Prophylaxis; S.aureus; Methicillin Resistant S.aureus (MRSA); Nasal carrier status
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Bacterial Infections
• Other Study ID Numbers: P128-001