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Study to Evaluate the Efficacy, Safety and Tolerability of 3% LTX-109 for Nasal Decolonisation of Staphylococcus Aureus

Primary Purpose

Nasal Decolonization of Staphylococcus Aureus

Status
Completed
Phase
Phase 2
Locations
Sweden
Study Type
Interventional
Intervention
Vehicle gel, 4 + 4 applications or 4 + 2 applications
LTX-109 3% gel, 4 + 4 applications
LTX-109 3% gel, 4 + 2 applications
Sponsored by
Pharma Holdings AS
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nasal Decolonization of Staphylococcus Aureus

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Willing and able to give written informed consent for participation in the study. Male or female subject aged 18 to 65 years, inclusive. Persistent nasal carrier of S. aureus (MSSA), confirmed by 2 positive bacterial cultures from the nose during the screening period. Medically healthy subjects without abnormal clinically significant medical history, physical findings, vital signs, or laboratory values at the time of screening, as judged by the Investigator. Women of child bearing potential (WOCBP) had to practice abstinence (only allowed when this was the preferred and usual lifestyle of the subject) or had to agree to use a highly effective method of contraception with a failure rate of < 1% to prevent pregnancy from the date of dosing until 2 weeks after last dose. Female subjects had to refrain from donating eggs from the date of dosing until 3 months after dosing with the IMP. Their male partner had to agree to use a condom from date of first dosing until 2 weeks after last dose if he had not undergone vasectomy. Male subjects had to be willing to use condom or had to be vasectomised or practice sexual abstinence to prevent pregnancy and drug exposure of a partner and had to refrain from donating sperm from the date of dosing until 3 months after dosing with the IMP. Their female partner of child-bearing potential had to use contraceptive methods with a failure rate of < 1% to prevent pregnancy (see above). Exclusion Criteria: History of any clinically significant disease or disorder which, in the opinion of the Investigator, could either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study. Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the administration of IMP. Severe eczema or skin wounds, dry or sensitive skin assessed as clinically significant by the Investigator. Any positive result at screening for serum hepatitis B surface antigen, hepatitis C antibody and HIV. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to LTX-109 or chlorhexidine. S. aureus (MSSA and/or MRSA) decolonisation attempt in the 6 months prior to - MRSA positive at screening (Visit 1 and/or Visit 2). Inability to take medications nasally. Nasal polyps or significant anatomical nasal abnormality, as judged by the Investigator. Evidence of open wound, lesion, inflammation, erythema or infection (including active rhinitis, sinusitis or upper respiratory infection or severe acne vulgaris) affecting the nostril area, lip and skin close to the nose. History of multiple episodes (>3) of epistaxis within 12 months prior to screening Visit 2. Disease in the region of the application sites, significant history of trauma or skin disease in the region of the application sites, current nasal skin or nasal septum condition requiring treatment or nasal surgery in the 6 months prior to screening Visit 2. In situ nasal jewellery or open nasal piercings. Previous or concurrent treatment with antimicrobials for an infection within the last 28 days prior to the first administration of IMP.

Sites / Locations

  • ClinSmart Sweden AB

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Active Comparator

Active Comparator

Arm Label

Placebo

Cohort 1

Cohort 2

Arm Description

Vehicle treatment

For all subjects, the IMP was applied 4 times during an intensive dosing regimen for 4 ½-hours (on Day 1 at 0, 1 ½, 3 and 4 ½ - hours). For subjects in Cohort 1, this was followed by 4 additional applications: on Day 1 at 12 hours, on Day 2 at 24 and 36 hours, and on Day 3 at 48 hours.

For all subjects, the IMP was applied 4 times during an intensive dosing regimen for 4 ½-hours (on Day 1 at 0, 1 ½, 3 and 4 ½ - hours). For subjects in Cohort 2 the IMP was likewise applied 4 times during the 4 ½-hour period (on Day 1 at 0, 1 ½, 3 and 4½ hours), but was followed by 2 applications: on Day 1 at 12 hours and on Day 2 at 36 hours.

Outcomes

Primary Outcome Measures

Operating Window Eradication
Number of subjects on LTX-109 versus placebo with bacterial eradication period lasting for 6 hours, from 6 to 12 hours after start of treatment (the "Operation Window").

Secondary Outcome Measures

Number eradicated at specific timepoints
Number of subjects on LTX-109 versus placebo with bacterial eradication at 4 ½, 6 and 12 hours after start of treatment.
Percentage change in colony forming units (CFUs) in subjects from baseline
Percentage change in colony forming units (CFUs) in subjects from baseline on LTX-109 versus placebo at 4 ½, 6 and 12 hours after start of treatment.
Number of subjects on LTX-109 versus placebo with bacterial eradication period lasting for 48 hours
Number of subjects on LTX-109 versus placebo with bacterial eradication period lasting for 48 hours, from 6 to 54 hours after start of treatment ("48 hours Eradication Window")
Adverse events
Occurrence and frequency of adverse events (AEs)
Local tolerability assessed by health care professional
Incidence of local reactions (erythema, swelling and lesions) will be assessed. Each nostril will be evaluated separately and each parameter will be scored using a 4-graded scale (0-3): 0: none,1: mild, 2: moderate, 3: severe
Local tolerability assessed by the subject
Incidence of local reactions (pruritus and discomfort) will be assessed by the subject. Each nostril will be evaluated separately using a visual analogue scale (VAS).
Asessment of Vital Signs (Systolic and diastolic blood pressure and pulse)
Systolic and diastolic blood pressure (BP) and pulse will be measured in supine position after 10 minutes of rest
Safety laboratory assessments
Blood samples for the analysis of clinical chemistry and haematology be collected through venepuncture or an indwelling venous catheter and sent to the certified clinical chemistry laboratory and analysed by routine analytical methods. Safety laboratory values will be specified and documented as normal, abnormal NCS, or abnormal CS in the eCRF. Abnormal values assessed by the Investigator as CS will be reported as AEs. Clinical chemistry parameters to be reported: Alanine aminotransferase (ALT),Albumin, Alkaline, phosphatase (ALP), Aspartate aminotransferase (AST), Bilirubin (total and conjugated), Calcium, Creatinine (eGFR included), Glucose, Phosphate, Potassium, Sodium, Urea. Haematology parameters to be reported: Red blood cell (RBC) count, White blood cell (WBC) count with differential count, Haematocrit (B-EVF), Haemoglobin (Hb), Platelet count.

Full Information

First Posted
May 2, 2023
Last Updated
May 25, 2023
Sponsor
Pharma Holdings AS
Collaborators
CTC Clinical Trial Consultants AB
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1. Study Identification

Unique Protocol Identification Number
NCT05889351
Brief Title
Study to Evaluate the Efficacy, Safety and Tolerability of 3% LTX-109 for Nasal Decolonisation of Staphylococcus Aureus
Official Title
A Phase IIa, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety and Tolerability of 3% LTX-109 Compared to Placebo for Nasal Decolonisation of Staphylococcus Aureus.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
September 19, 2022 (Actual)
Primary Completion Date
October 28, 2022 (Actual)
Study Completion Date
October 28, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharma Holdings AS
Collaborators
CTC Clinical Trial Consultants AB

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
A Phase IIa, double-blind, placebo-controlled, randomised study designed to evaluate the efficacy, safety and tolerability of two dosing regimens with LTX-109 administered topically to the anterior nares in subjects with persistent carriage of Staphylococcus aureus (S. aureus).
Detailed Description
Approximately 90 subjects planned screened to achieve 27 randomised and dosed subjects with persistent S. aureus carriage. On Day 1, subject randomisation in a 2:1 ratio to receive either LTX-109 (n=18) or placebo (n=9). Cohort (1 [8 doses] or 2 [6 doses]) used as a stratification variable to preserve the 2:1 treatment randomisation ratio in each cohort (LTX-109 n=9 or placebo n=5/4). For all subjects, the IMP was to be applied 4 times during an intensive dosing regimen for 4 ½-hours (on Day 1 at 0, 1 ½, 3 and 4 ½ - hours). For subjects in Cohort 1, this was followed by 4 additional applications: on Day 1 at 12 hours, on Day 2 at 24 and 36 hours, and on Day 3 at 48 hours. For subjects in Cohort 2 the IMP was likewise applied 4 times during the 4 ½-hour period (on Day 1 at 0, 1 ½, 3 and 4½ hours), but was followed by 2 applications: on Day 1 at 12 hours and on Day 2 at 36 hours. On each dosing occasion, a large drop (approximately 250 μL) of IMP was applied into each nostril and distributed to cover the whole area of the nostril. The subjects were carefully monitored by clinical staff during and after dosing. Safety assessments (AEs, vital signs, safety laboratory assessments and local tolerability) and efficacy assessments (nasal swab) were performed. All subjects were instructed to wash the body and hair with chlorhexidine body wash and shampoo at the CRU on Day 1 (prior to the first dose) and on Day 2. Subjects were provided with chlorhexidine body wash and shampoo for body and hair wash at home on Day 3, Day 4, Day 5, Day 6 and Day 7. On Day 3 and Day 7, subjects used the chlorhexidine shower before the visits to the CRU. A final end-of-study visit (Visit 5) took place on Day 7 (+2 days) or after early withdrawal.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nasal Decolonization of Staphylococcus Aureus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomised, Double-blind, Placebo-controlled Randomization 2:1, active to placebo
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Vehicle treatment
Arm Title
Cohort 1
Arm Type
Active Comparator
Arm Description
For all subjects, the IMP was applied 4 times during an intensive dosing regimen for 4 ½-hours (on Day 1 at 0, 1 ½, 3 and 4 ½ - hours). For subjects in Cohort 1, this was followed by 4 additional applications: on Day 1 at 12 hours, on Day 2 at 24 and 36 hours, and on Day 3 at 48 hours.
Arm Title
Cohort 2
Arm Type
Active Comparator
Arm Description
For all subjects, the IMP was applied 4 times during an intensive dosing regimen for 4 ½-hours (on Day 1 at 0, 1 ½, 3 and 4 ½ - hours). For subjects in Cohort 2 the IMP was likewise applied 4 times during the 4 ½-hour period (on Day 1 at 0, 1 ½, 3 and 4½ hours), but was followed by 2 applications: on Day 1 at 12 hours and on Day 2 at 36 hours.
Intervention Type
Drug
Intervention Name(s)
Vehicle gel, 4 + 4 applications or 4 + 2 applications
Intervention Description
Control arm/placebo
Intervention Type
Drug
Intervention Name(s)
LTX-109 3% gel, 4 + 4 applications
Intervention Description
Cohort 1 active treatment
Intervention Type
Drug
Intervention Name(s)
LTX-109 3% gel, 4 + 2 applications
Intervention Description
Cohort 2 active treatment
Primary Outcome Measure Information:
Title
Operating Window Eradication
Description
Number of subjects on LTX-109 versus placebo with bacterial eradication period lasting for 6 hours, from 6 to 12 hours after start of treatment (the "Operation Window").
Time Frame
6 hour to 12 hours after start of treatment
Secondary Outcome Measure Information:
Title
Number eradicated at specific timepoints
Description
Number of subjects on LTX-109 versus placebo with bacterial eradication at 4 ½, 6 and 12 hours after start of treatment.
Time Frame
4.5 hours, 6 hours, 12 hours
Title
Percentage change in colony forming units (CFUs) in subjects from baseline
Description
Percentage change in colony forming units (CFUs) in subjects from baseline on LTX-109 versus placebo at 4 ½, 6 and 12 hours after start of treatment.
Time Frame
4.5 hours, 6 hours, 12 hours
Title
Number of subjects on LTX-109 versus placebo with bacterial eradication period lasting for 48 hours
Description
Number of subjects on LTX-109 versus placebo with bacterial eradication period lasting for 48 hours, from 6 to 54 hours after start of treatment ("48 hours Eradication Window")
Time Frame
From 6 hours to 54 hours after start of treatment
Title
Adverse events
Description
Occurrence and frequency of adverse events (AEs)
Time Frame
Through treatment and followup of 7 days
Title
Local tolerability assessed by health care professional
Description
Incidence of local reactions (erythema, swelling and lesions) will be assessed. Each nostril will be evaluated separately and each parameter will be scored using a 4-graded scale (0-3): 0: none,1: mild, 2: moderate, 3: severe
Time Frame
Pre-dose, 1.5 hours, 4.5 hours, 6 hours, 12, hrs, 54 hours and Day 7
Title
Local tolerability assessed by the subject
Description
Incidence of local reactions (pruritus and discomfort) will be assessed by the subject. Each nostril will be evaluated separately using a visual analogue scale (VAS).
Time Frame
Pre-dose, 1.5 hours, 4.5 hours, 6 hours, 12, hrs, 54 hours and Day 7
Title
Asessment of Vital Signs (Systolic and diastolic blood pressure and pulse)
Description
Systolic and diastolic blood pressure (BP) and pulse will be measured in supine position after 10 minutes of rest
Time Frame
24 hours, 54 hours and Day 7
Title
Safety laboratory assessments
Description
Blood samples for the analysis of clinical chemistry and haematology be collected through venepuncture or an indwelling venous catheter and sent to the certified clinical chemistry laboratory and analysed by routine analytical methods. Safety laboratory values will be specified and documented as normal, abnormal NCS, or abnormal CS in the eCRF. Abnormal values assessed by the Investigator as CS will be reported as AEs. Clinical chemistry parameters to be reported: Alanine aminotransferase (ALT),Albumin, Alkaline, phosphatase (ALP), Aspartate aminotransferase (AST), Bilirubin (total and conjugated), Calcium, Creatinine (eGFR included), Glucose, Phosphate, Potassium, Sodium, Urea. Haematology parameters to be reported: Red blood cell (RBC) count, White blood cell (WBC) count with differential count, Haematocrit (B-EVF), Haemoglobin (Hb), Platelet count.
Time Frame
54 hours and Day 7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Willing and able to give written informed consent for participation in the study. Male or female subject aged 18 to 65 years, inclusive. Persistent nasal carrier of S. aureus (MSSA), confirmed by 2 positive bacterial cultures from the nose during the screening period. Medically healthy subjects without abnormal clinically significant medical history, physical findings, vital signs, or laboratory values at the time of screening, as judged by the Investigator. Women of child bearing potential (WOCBP) had to practice abstinence (only allowed when this was the preferred and usual lifestyle of the subject) or had to agree to use a highly effective method of contraception with a failure rate of < 1% to prevent pregnancy from the date of dosing until 2 weeks after last dose. Female subjects had to refrain from donating eggs from the date of dosing until 3 months after dosing with the IMP. Their male partner had to agree to use a condom from date of first dosing until 2 weeks after last dose if he had not undergone vasectomy. Male subjects had to be willing to use condom or had to be vasectomised or practice sexual abstinence to prevent pregnancy and drug exposure of a partner and had to refrain from donating sperm from the date of dosing until 3 months after dosing with the IMP. Their female partner of child-bearing potential had to use contraceptive methods with a failure rate of < 1% to prevent pregnancy (see above). Exclusion Criteria: History of any clinically significant disease or disorder which, in the opinion of the Investigator, could either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study. Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the administration of IMP. Severe eczema or skin wounds, dry or sensitive skin assessed as clinically significant by the Investigator. Any positive result at screening for serum hepatitis B surface antigen, hepatitis C antibody and HIV. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to LTX-109 or chlorhexidine. S. aureus (MSSA and/or MRSA) decolonisation attempt in the 6 months prior to - MRSA positive at screening (Visit 1 and/or Visit 2). Inability to take medications nasally. Nasal polyps or significant anatomical nasal abnormality, as judged by the Investigator. Evidence of open wound, lesion, inflammation, erythema or infection (including active rhinitis, sinusitis or upper respiratory infection or severe acne vulgaris) affecting the nostril area, lip and skin close to the nose. History of multiple episodes (>3) of epistaxis within 12 months prior to screening Visit 2. Disease in the region of the application sites, significant history of trauma or skin disease in the region of the application sites, current nasal skin or nasal septum condition requiring treatment or nasal surgery in the 6 months prior to screening Visit 2. In situ nasal jewellery or open nasal piercings. Previous or concurrent treatment with antimicrobials for an infection within the last 28 days prior to the first administration of IMP.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johan Nilsson, MD, Phd
Organizational Affiliation
ClinSmart AB
Official's Role
Principal Investigator
Facility Information:
Facility Name
ClinSmart Sweden AB
City
Uppsala
ZIP/Postal Code
SE-752 37
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study to Evaluate the Efficacy, Safety and Tolerability of 3% LTX-109 for Nasal Decolonisation of Staphylococcus Aureus

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