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

NCT ID: NCT01746654

Last Updated: 2016-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2015-12-31

Brief Summary

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.

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.

Conditions

Infectious Disease; Bacterial Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

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)

Group Type: EXPERIMENTAL

P128-0.1 mg

Intervention Type: DRUG

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.

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)

Group Type: EXPERIMENTAL

P128-0.3 mg

Intervention Type: DRUG

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.

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)

Group Type: EXPERIMENTAL

P128-1.0 mg

Intervention Type: DRUG

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.

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)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo was administered to both nares once in part A, multiple times in Part B and Part C, Once in part D

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Placebo

Placebo was administered to both nares once in part A, multiple times in Part B and Part C, Once in part D

Intervention Type: DRUG

Other Intervention Names

Single dose in Part A; Multiple doses in Part B; Multiple doses in Part C; Single dose in Part D; Single dose in Part A; Multiple doses in Part B; Multiple doses in Part C; Single dose in Part D; Single dose in Part A; Multiple doses in Part B; Multiple doses in Part C; Single dose in Part D; Single dose in Part A; Multiple doses in Part B; Multiple doses in Part C; Single dose in Part D

Eligibility Criteria

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

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GangaGen, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dale A Fisher, MBBS, FRACP

Role: PRINCIPAL_INVESTIGATOR

National University Hospital, Singapore

Surinder Kher, MD

Role: STUDY_DIRECTOR

Manipal Acunova Ltd, Bangalore

Locations

National University Hospital

Singapore, , Singapore

Countries

Singapore

Other Identifiers

P128-001

Identifier Type: -

Identifier Source: org_study_id