A Phase 1 Investigator Initiated Study to Evaluate the Safety, Tolerability and Preliminary Effectiveness of AB-SA01 in Patients with Chronic Rhinosinusitis Associated with Staphylococcus aureus Infection
The Queen Elizabeth Hospital
9 participants
Dec 9, 2015
Interventional
Conditions
Summary
CRS is a debilitating inflammatory and infection based condition, affecting up to 9% of the Australian population (AIHW, 2010). Currently available therapies to treat this condition include steroids, antibiotics and surgical intervention (Fokkens et al., 2012). Unfortunately there remains a cohort of patients that are resistant to both medical and surgical interventions who experience persistent CRS symptoms, which is termed recalcitrant CRS (rCRS). The presence of bacterial biofilms in the sinonasal tract is one aspect of the condition shown to contribute to this recalcitrance and symptom persistence. Biofilms are 1000-fold more resistant to antibiotics compared to non-biofilm bacterial, making them resistant to the current place antibiotic therapies that are used to treat infections in CRS. There is, therefore, a need to develop novel therapies that are effective against these biofilms if we are to succeed in treating these rCRS patients. Bacteriophage-based treatment, AB-SA01, could be the answer to the problem of biofilms in rCRS. Bacteriophages or phages, identified almost 100 years ago, are bacterial viruses that specifically target bacterial cells, leading to cell death. Given their specific mechanism of action, bacteriophages are not able to infect mammalian cells, and have thus far shown few adverse effects when applied to humans for use as antimicrobial treatments (Chanisvilli, 2012; Brussow, 2005). The Primary endpoint of the study is to: 1. To assess the safety and tolerability of three dosage regimens of AB-SA01 in patients with Chronic Rhinosinusitis associated with Staphylococcus aureus infection. The secondary objectives of the study are: 2. The preliminary assessment of effectiveness of three dosage regimens of AB-SA01 by endoscopic evaluation by the Investigator using the Lund-Kennedy scale. 3. The preliminary assessment of effectiveness of three dosage regimens of AB-SA01 by patient assessment of symptoms.
Eligibility
Inclusion Criteria11
- Participants must have had at least two of the following symptoms of chronic rhinosinusitis (nasal discharge, postnasal drip, nasal obstruction, facial pain and pressure or lack of sense of smell) that has been previously persistent for greater than 3 months.
- Participants must have had at least one operation for their chronic rhinosinusitis but should be at least 6 weeks post- operative.
- Participants must have a positive sinonasal swab that indicates infection of S. aureus in the sinuses that is sensitive to AB-SA01 within 14 days of enrolment.
- Participants must show evidence of chronic sinusitis by direct endoscopic examination.
- Participants must have the ability to administer nasal lavage twice daily for the duration of the treatment period.
- Participants must have impaired quality of life as measured by RSDI.
- Participants must be male or female aged between 18 and 70 years.
- Participants must be able to give written informed consent.
- Participants must have the ability and willingness to attend several visits to the study centre.
- Participants must have the willingness and ability to comply with the requirements of the protocol as determined by the Investigator.
- Participants using highly effective, double barrier contraception (both male and female partners) during the study and for 1 month following the dose of AB-SA01.
Exclusion Criteria9
- 1. Participants with a diagnosis of cystic fibrosis or ciliary dyskinesia.
- Female participants who are pregnant or breastfeeding.
- Participants who are immunocompromised.
- Participants who are actively taking oral steroids or antibiotics.
- Participants who have used antibiotics within 1 month prior to screening.
- Participants who have been on active trial therapy within one month of screening.
- Participants who have a positive sinonasal swab that indicates presence of P. aeruginosa in the sinuses.
- Any clinically significant laboratory abnormality.
- Participants who are unlikely to comply with the study protocol or, in the opinion of the investigator, would not be a suitable candidate for participation in the study.
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Interventions
Investigator initiated, single-centre, safety study to evaluate the safety and preliminary effectiveness of three dosage regimens of AB-SA01 in patients with chronic rhinosinusitis associated with Staphylococcus aureus Infection. This is a first in human (FIH) study. A total of 9 participants will be enrolled in the study. Three (3) cohorts of three (3) patients will be serially dosed with AB-SA01 by nasal douche in the following three (3) dosage regimens: Cohort 1: Twice daily for a period of 7 days with phage at a concentration of 3x10^8 pfu prepared in 240 mL of a NeilMed sinus rinse Cohort 2: Twice daily for a period of 14 days with phage at a concentration of 3x10^8 pfu prepared in 240 mL of a NeilMed sinus rinse Cohort 3: Twice daily for a period of 14 days with phage at a concentration of 3x10^9 pfu The investigational product, AB-SA01, is a sterile solution containing three active lytic S. aureus bacteriophages: Sa87, Sa83 and J-Sa36. The biological material subject of the Application to Import Biological Materials is a therapeutic bacteriophage (phage) mix consisting of three individual (Sa87, Sa83 and J-Sa36) naturally occurring, not genetically modified, Staphylococcus aureus phages. To ensure adherence to the intervention, patients will be given detailed instructions of how to use the product and follow up calls during the treatment will be made to ensure there is no confusion. Further to this patients will be asked to return all used and unused vials at the completion of the study, at which time they will also be asked questions specifically about compliance.
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ACTRN12616000002482