A Phase I/IIa Study to Evaluate the Safety, Tolerability and Efficacy of Topical LTX-109 in Subjects Nasally Colonized With Methicillin-resistant/-Sensitive Staphylococcus Aureus (MRSA/MSSA)

A Randomised, Double-blind, Placebo-controlled, Ascending Dose Phase I/IIa Study to Evaluate the Safety, Tolerability and Efficacy of Topical LTX-109 in Subjects Nasally Colonized With Methicillin-resistant/-Sensitive Staphylococcus Aureus (MRSA/MSSA)

This is a pilot study conducted to evaluate the safety, local tolerability and efficacy of LTX-109(Lytixar™), a lytic peptide designed to kill bacterias quickly and efficient. LTX-109 (Lytixar™)will be applied in the anterior nares in subjects who are carriers of nasal colonies of MRSA/MSSA.

The extent of systemic absorption of LTX -109 when applied to the anterior nares will be evaluated and the effect of Lytixar™ as to clear colonies of MRSA/MSSA during the the observation period and Week 2 to Week 9 after treatment.

Study Overview

• Status: Completed
• Conditions: Nasal Carriers MRSA
• Intervention / Treatment: Drug: LTX-109

Detailed Description

Subjects with persistent colonies of MRSA/MSSA in the nostril will be recruited to receive either active treatment or placebo. This is a dose escalating study. First grout will receive either 1% Lytixar™ or placebo, next group 2% Lytixar™ or placebo and finally 5% Lytixar™ or placebo. Dose escalation will be performed after a brief safety evaluation of the tolerability after application of Lytixar™/placebo vehicle TID for three days. Pharmacokinetic samples will be collected from subjects who are willing. Subjects will be followed until 9 weeks after initiation of treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Malmö, Sweden, 205 02
    • Skane University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 75 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female subjects between the ages of 16 and 75, inclusive.
• Female subjects must be non-pregnant, non-lactating.
• Female subjects of child bearing potential and male subjects with female partners of child-bearing potential must use an adequate form of diaphragm or condom with spermicidal prior to entry into the study and two weeks following the completion of all follow-up procedures 9 weeks after treatment. Hormone contraception or hormonal IUDs alone are not acceptable contraception
• Signed and dated written informed consent by subject.
• Subject's medical condition is stable, with no clinically significant abnormalities.
• Subject's pre-study laboratory screen of haematology, clinical chemistry and urinalysis are normal or if abnormal, not considered clinically significant.
• Subjects must be able to understand the subject information and the consent form, and be willing to return to the study site for follow up visits, comply with requirements, instructions and restrictions of the study listed in the informed consent form.
• All family members, to a subject carrying MRSA (not applicable for MSSA positive) should also be screened for MRSA. Subjects that are eligible may be included in the study, and family members not eligible or willing to participate should be offered treatment for decolonization of MRSA according to standard treatment and investigators choice.

Exclusion Criteria:

• Negative nasal culture for MRSA/MSSA on the first screen visit.
• Negative nasal cultures for MRSA/MSSA at any occasion during the run-in period day -14 to -3 day prior to Baseline.
• Severe eczema (eczema infected with MRSA) or skin wounds, clinically significant according to investigator.
• Previous or concurrent treatment with antimicrobials for an infection within the last 28 days prior to baseline.
• MRSA decolonization attempt in the previous 6 months (prior treatment for a MRSA infection is not an exclusion criterion).
• Systolic BP is ≥170 mmHg, or diastolic BP is ≥100 mmHg or HR is ≥110 bpm.
• Inability to take medications nasally.
• Evidence of active rhinitis, sinusitis, or upper respiratory infection.
• 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 previous 3 months.
• Significant ongoing or history of drug or alcohol abuse in the opinion of the investigator makes the subject unsuitable for enrolment.
• Use of prescription or non prescription drugs within minimum 7 days prior to the first dose of study medication. Subjects on stable doses of non-prescription painkillers, anti-inflammatory drugs (such as paracetamol and NSAIDs), oral antidiabetics or insulin may be allowed to be included to the study at the discretion of the investigator.
• Known allergic reactions or hypersensitivity of significant severity in general and specifically to any component of the study medication.
• Systemic illness requiring treatment within 28 days prior to baseline.
• Clinically significant illness (defined by the investigator) in the past 4 weeks before the Screening visit.
• Current or history of significant hepatic, renal, endocrine, cardiac, nervous, psychiatric, gastrointestinal, pulmonary, haematological, or metabolic disorder that is not in a stable condition. Malignancy <5 years since final treatment.
• Current or history of any significant disease or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
• Known positive test for Human Immunodeficiency Virus (HIV) antibody, hepatitis B virus surface antigen or hepatitis C virus antibody.
• Other unspecified reasons that, in the opinion of the investigator make the subject unsuitable for enrolment.
• Treatment with an investigational drug within 30 days prior to the first dose of study medication.

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: TRIPLE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LTX-109 (Lytixar); Ascending dose study. Start enrollment to group 1: 1% LTX-109/placebo, then group 2: 2%LTX-109/placebo and finally group 3: 5%LTX-109/placebo dosed in each nostril TID for 3 consecutive days.	Drug: LTX-109; 1%, 2% and 3% Lytixar (gel formulation). TID for 3 days.; Other Names: Lytixar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local tolerability in the anterior nares	To explore safety, local tolerability and efficacy of LTX-109 when applied topically into the anterior nares in subjects with nasal colonisation of MRSA/MSSA. To determine the extent of systemic absorption of LTX -109 when applied to the anterior nares.	Day 1, 2, 3. week 2-9 after final treatment.

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate recurrence of MRSA/MSSA during the observation period.	Week 2 to Week 9 after treatment.

Collaborators and Investigators

• Sponsor: Lytix Biopharma AS
• Investigators: Principal Investigator: Anna Nilsson, MD, PhD, Skåne University Hospital, Malmö

Publications and helpful links

General Publications

• Nilsson AC, Janson H, Wold H, Fugelli A, Andersson K, Hakangard C, Olsson P, Olsen WM. LTX-109 is a novel agent for nasal decolonization of methicillin-resistant and -sensitive Staphylococcus aureus. Antimicrob Agents Chemother. 2015 Jan;59(1):145-51. doi: 10.1128/AAC.03513-14. Epub 2014 Oct 20.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (ACTUAL): April 1, 2011
• Study Completion (ACTUAL): April 1, 2011

Study Registration Dates

• First Submitted: July 7, 2010
• First Submitted That Met QC Criteria: July 7, 2010
• First Posted (ESTIMATE): July 8, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): June 8, 2011
• Last Update Submitted That Met QC Criteria: June 7, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: MRSA; nose
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity
• Other Study ID Numbers: C10-109-02