Phase II year
2009
(last award dollars: 2010)
Phase II Amount
$2,618,973
Increasing use of intravascular (IV) catheters put patients at risk for catheter occlusion as well as systemic infections. Failure to prevent and treat device-related infections is due to the ability of microorganisms (fungi and bacteria) to produce biofilms, resulting in catheter-associated infection and occlusion. Biofilms formed on catheters are complex structures composed of host-derived fibrin deposits and stranding as well as pathogen- derived, extracellular polysaccharide-rich matrix. There is a significant unmet need to prevent and treat biofilm- related infections. To address this unmet need, in this SBIR application, we will develop and commercialize an antibiofilm product that possesses anti-biofilm and anti-coagulation/anti-catheter occlusion properties. Our product, B-LockTM, discovered using our previously established in vitro and in vivo assays meets the above criteria. We demonstrated that B-LockTM has broad-spectrum activity against biofilms formed by clinically relevant pathogens, both in vitro and in vivo, and also possesses anti-coagulant activity. Since the last submission, we successfully identified six prototype formulations that remained physically and chemically stable for several months, showed that clinical candidate was active against biofilms in vitro and in vivo, including biofilms formed by fluconazole-resistant C. albicans and C. parapsilosis, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE). In this Fast-Track SBIR application, we propose a two-phase plan to develop B-LockTM as a product directed at prevention and treatment of CRBSIs and occlusion. Phase 1 of this SBIR application describes in vivo efficacy testing, stability testing, toxicology and compatibility studies, while Phase 2 details a clinical trial to test the safety and efficacy of B-LockTM. PHASE 1 SPECIFIC AIMS: The objective of Phase 1 of this Fast-Track application is to perform expanded in vivo efficacy testing, evaluate the in vitro activity of B-LockTM against biofilms formed by drug-resistant microorganisms, and determine the long-term stability of the clinical candidate. Furthermore, we will also evaluate the safety profile of B-LockTM and determine its compatibility with catheter material. The following specific aims are proposed: Aim 1. Determine efficacy of clinical B-LockTM formulation in vivo. Aim 2. Evaluate long-term stability of B-LockTM. Aim 3. Evaluate the in vitro activity of B-LockTM against biofilms formed by drug-resistant microorganisms. Aim 4. Demonstrate that B-LockTM is safe and non-toxic in vivo. Aim 5. Demonstrate compatibility of B-LockTM with catheter materials. PHASE 2 SPECIFIC AIM. Conduct a randomized, double-blind clinical trial to evaluate B-LockTM solution compared with heparin lock solution in the preservation of in-dwelling catheter sterility and potency in patients receiving chemotherapy for hematologic malignancies.
Public Health Relevance: Central venous catheters (CVCs) are essential tools for the appropriate treatment and support of patients with life-threatening diseases such as cancer and end-stage kidney failure. However, intravascular catheters put patients at risk for systemic infections, which are caused by microbial biofilms formed within the catheter lumens. In this Fast-Track SBIR application, we propose a two-phase plan to develop an antibiofilm and anticoagulant product (B-LockTM) directed at prevention and treatment of CVC-associated infections and occlusion.
Project Terms: 21+ years old; Acute; Address; Adult; Age; Animals; Anticoagulant Agents; Anticoagulant Drugs; Anticoagulants; Assay; Bacteremia; Bacteria; Binding; Binding (Molecular Function); Bioassay; Biologic Assays; Biological; Biological Assay; Biological Preservation; Blood; Budgets; C. albicans; C.albicans; Cancer Treatment; Cancer, Oncology; Cancers; Candida; Candida albicans; Catheters; Cellular injury; Childhood; Clinical; Clinical Management; Clinical Research; Clinical Study; Clinical Trials; Clinical Trials, Unspecified; Clinics and Hospitals; Clinics or Hospitals; Clotting; Coagulants; Coagulation; Coagulation Process; Collaborations; Common Rat Strains; Complex; Conduct Clinical Trials; Cyclic GMP; Data Set; Dataset; Deposit; Deposition; Development; Devices; Disease; Disorder; Double-Blind Method; Double-Blind Study; Double-Blinded; Double-Masked Method; Double-Masked Study; Drug Formulations; Drug resistance; Drugs; Endothelial Cells; Ensure; Evaluation; Exposure to; FLR; Failure (biologic function); Fee-for-Service Plans; Fees for Service; Fibrin; Fluconazole resistance; Fluconazole resistant; Formulation; Formulations, Drug; Funding; Fungemia; Glycans; Guanosine Cyclic 3',5'-Monophosphate; Guanosine Cyclic Monophosphate; Guanosine, cyclic 3',5'-(hydrogen phosphate); Guidelines; Health Care Providers; Health Personnel; Healthcare Providers; Healthcare worker; Hematologic Cancer; Hematologic Malignancies; Hematologic Neoplasms; Hematological Malignancies; Hematological Neoplasms; Hematological Tumor; Hematopoietic Cancer; Hemodialyses; Hemodialysis; Heparin; Heparinic Acid; Human, Adult; INFLM; Immunocompromised; Immunocompromised Host; Immunocompromised Patient; Immunosuppressed Host; Implantable Catheters; In Vitro; In-Dwelling Catheters; Incidence Study; Industry; Indwelling Catheter; Infection; Inflammation; Injury; International; Kentucky; Kidney Failure; Kidney Insufficiency; Laboratories; Laboratory Research; Life; MRSA; Malignant Hematologic Neoplasm; Malignant Neoplasm Therapy; Malignant Neoplasm Treatment; Malignant Neoplasms; Malignant Tumor; Mammals, Rabbits; Mammals, Rats; Marketing; Mechanics; Medical center; Medication; Methicillin Resistant S. Aureus; Methicillin Resistant Staphylococcus Aureus; Methods; Microbial Biofilms; Microorganisms, General; Modeling; Molecular Interaction; Monilia; Monitor; Mycology; NIH; National Institutes of Health; National Institutes of Health (U.S.); Ohio; Organism; Oryctolagus cuniculus; Out-patients; Outpatients; Patient Recruitments; Patients; Pharmaceutic Preparations; Pharmaceutical Agent; Pharmaceutical Preparations; Pharmaceuticals; Pharmacologic Substance; Pharmacological Substance; Phase; Pilot Projects; Polysaccharides; Position; Positioning Attribute; Preparation; Preservation, Biologic; Preservation, Biological; Prevention; Programs (PT); Programs [Publication Type]; Property; Property, LOINC Axis 2; Rabbit, Domestic; Rabbits; Randomized; Randomized Clinical Trials; Rat; Rattus; Renal Failure; Renal Insufficiency; Research; Research Contracts; Resistance; Reticuloendothelial System, Blood; Risk; SBIR; SBIRS (R43/44); Safety; Science; Secure; Serial Passage; Site; Small Business Innovation Research; Small Business Innovation Research Grant; Solutions; Source; Staging; Standardization; Sterility; Structure; Supportive Therapy; Supportive care; Surrogate Markers; Systemic infection; Technology; Temperature; Test Result; Testing; The science of Mycology; Thrombosis; TimeLine; Toxic effect; Toxicities; Toxicology; United States National Institutes of Health; Universities; Vancomycin resistant enterococcus; Vancomycin-resistant enterococci; Vascular Endothelial Cell; Veins; Venous; Venous Reservoirs; adult human (21+); anticancer therapy; bacteraemia; base; biofilm; blood thinner; cGMP; cancer therapy; candida biofilm; cell damage; cell injury; chemical release; chemical stability; chemotherapy; clinical efficacy; clinical investigation; clinical relevance; clinical research site; clinical site; clinically relevant; commercialization; conference; cost; design; designing; disease/disorder; drug resistant; drug resistant microorganism; drug/agent; efficacy testing; experience; extracellular; failure; fungaemia; fungus; guanosine 3'5' monophosphate; health care personnel; health care worker; health provider; healthcare personnel; high risk; immunosuppressed patient; in vitro activity; in vivo; living system; malignancy; medical personnel; meetings; member; methicillin resistant Staphylococcus aureus (organism); microorganism; neoplasm/cancer; oncology; pathogen; pediatric; pilot study; pre-clinical; preclinical; preservation; prevent; preventing; professor; programs; prospective; prototype; randomisation; randomization; randomly assigned; resistance to Drug; resistant; resistant to Drug; safety testing; stability testing; standard of care; sterile; success; symposium; thrombopoiesis inhibitor; tool; treatment provider
