A Phase I/IIa, double-blind, placebo-controlled, randomised study designed to evaluate the safety, tolerability, exploratory efficacy and exposure of LTX-109 administered topically to the anterior nares in subjects with persistent carriage of S. aureus (methicillin-susceptible S. aureus \[MSSA\] and/or methicillin-resistant S. aureus \[MRSA\]).
Approximately 60 subjects will be screened to achieve 24 persistent MSSA and/or MRSA carriers and 16 randomised and dosed subjects randomized 3:1, active to placebo. Eligible subjects will be admitted to the clinic on Day 1 for randomisation and dosing and will remain at the clinic until Day 2. Following nasal and perineum swabs and a chlorhexidine (Hibiscrub®) shower, the investigational medicinal product (IMP) will be applied topically to both nostrils by a qualified health professional 4 times during a six hour period (every two hours at 0, 2, 4 and 6 hours) on Day 1. Subjects will come back to the research clinic on Day 3, Day 4, Day 8 and Day 15 (Visits 4 to 7) for safety, tolerability and efficacy assessments and for blood sampling for bioanalysis. On Day 5 and Day 6, subjects will take a chlorhexidine shower at home. A final end-of-study visit (Visit 8) will take place on Day 22 (±3 days) or after early withdrawal. All subjects will be instructed to wash the body and hair with chlorhexidine body wash and shampoo at the clinic on Day 1 (prior to the first dose) and on Day 2. Prior to leaving the clinic on Day 2, subjects will be provided with chlorhexidine body wash and shampoo for body and hair wash at home on Day 3 (prior to Visit 4), on Day 4 (prior to Visit 5) and on Day 5 and Day 6. Each subject is expected to participate in the study for approximately 50 days including a 28 day screening period
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
15
LTX-109 gel will be applied topically to both nostrils by a qualified health professional. On each dosing occasion, a large drop of IMP will be applied into each nostril and distributed to cover the whole area of the nostril.
Placebo gel will be applied topically to both nostrils by a qualified health professional. On each dosing occasion, a large drop of IMP will be applied into each nostril and distributed to cover the whole area of the nostril.
ClinSmart Sweden AB
Uppsala, Sweden
Assessment of safety by occurence and frequency of Adverse Events
Occurrence and frequency of Adverse Events
Time frame: Through treatment and followup of 22 days
Local tolerability assessed by a qualified health care professional by evaluation of nostrils and scoring using a 4-point graded scale.
Incidence of local reactions (erythema, swelling and lesions) will be assessed by a qualified health care professional . Each nostril will be evaluated separately and scored using a 4-graded scale (0-3)
Time frame: Day 1
Local tolerability assessed by a qualified health care professional by evaluation of nostrils and scoring using a 4-point graded scale.
Incidence of local reactions (erythema, swelling and lesions) will be assessed by a qualified health care professional . Each nostril will be evaluated separately and scored using a 4-graded scale (0-3)
Time frame: Day 2
Local tolerability assessed by a qualified health care professional by evaluation of nostrils and scoring using a 4-point scale.
Incidence of local reactions (erythema, swelling and lesions) will be assessed by a qualified health care professional . Each nostril will be evaluated separately and scored using a 4-graded scale (0-3)
Time frame: Day 3
Local tolerability assessed by a qualified health care professional by evaluation of nostrils and scoring using a 4-point scale.
Incidence of local reactions (erythema, swelling and lesions) will be assessed by a qualified health care professional . Each nostril will be evaluated separately and scored using a 4-graded scale (0-3)
Time frame: Day 4
Local tolerability assessed by a qualified health care professional by evaluation of nostrils and scoring using a 4-point scale.
Incidence of local reactions (erythema, swelling and lesions) will be assessed by a qualified health care professional . Each nostril will be evaluated separately and scored using a 4-graded scale (0-3)
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Time frame: Day 8
Local tolerability assessed by a qualified health care professional by evaluation of nostrils and scoring using a 4-point scale.
Incidence of local reactions (erythema, swelling and lesions) will be assessed by a qualified health care professional . Each nostril will be evaluated separately and scored using a 4-graded scale (0-3)
Time frame: Day 15
Local tolerability assessed by a qualified health care professional by evaluation of nostrils and scoring using a 4-point scale.
Incidence of local reactions (erythema, swelling and lesions) will be assessed by a qualified health care professional . Each nostril will be evaluated separately and scored using a 4-graded scale (0-3)
Time frame: Day 22
Local tolerability assessed by the subject by Visual Analog Scale.
Assessment of Local tolerability on Visual Analog Scale
Time frame: Day 1
Local tolerability assessed by the subject by Visual Analog Scale.
Assessment of Local tolerability on Visual Analog Scale
Time frame: Day 2
Number of subjects on LTX-109 versus placebo with bacterial eradication at Test of Cure
Assessment of eradication of bacteria defined as non-presence of Staphylococcus aureus (MSSA and/or MRSA) in quantitative cultures
Time frame: 54 hours (+ 2 hours)
Number of subjects on LTX-109 versus placebo with bacterial eradication at other specified time points than Time of Cure.
Assessment of bacterial count at specified points in time to explore effect of the intervention
Time frame: 4, 6, 12, 24, 78 hours and Days 8, 15 and 22
Number of colony forming units (CFUs) in subjects on LTX-109 versus placebo at specified points in time.
Assessment of bacterial count at specified points in time to explore effect of the intervention
Time frame: 4, 6, 12, 24, 78 hours and Days 8, 15 and 22
Number of subjects on LTX-109 vs placebo with bacterial recolonisation defined as the timepoint of recurrence of colonisation after confirmed eradication.
Assessment of recurrence
Time frame: Days 4, 8, 15 and 22
Plasma concentrations of LTX-109
Assessment of plasma concentratin by analysis of blood samples
Time frame: 6, 24, 54 and 78 hours