Oral Phage Therapy for Enterococcus Colonization

Overseen By Ellie Morell

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Intralytix, Inc.

Must not be taking: Antidiarrheals, Antimicrobials, Antacids, Probiotics

Disqualifiers: Pregnancy, Heart disease, Gastrointestinal illness, others

Compensation: Varies

Number of Visits: Unknown

80 Participants Needed

Trial Summary

What is the purpose of this trial?

The study is a first-in-human Phase 1/2a randomized, double-blind, placebo-controlled trial to assess the clinical safety and efficacy of VRELysin in healthy and VRE-colonized adults.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications, such as oral or intravenous antimicrobials, proton pump inhibitors, H2 blockers, antacids, and supplemental probiotics, before and during the study. If you regularly use these or similar medications, you may need to stop them to participate.

What data supports the effectiveness of the treatment VRELysin™ for Enterococcus colonization?

Research shows that phage therapy, which uses viruses to target bacteria, can be effective against antibiotic-resistant Enterococcus infections. Phages have a lower chance of resistance development compared to antibiotics and can specifically target harmful bacteria without affecting beneficial ones. ^{1 2 3 4 5}

How is the treatment VRELysin™ different from other treatments for Enterococcus colonization?

VRELysin™ is unique because it uses bacteriophages, which are viruses that specifically target and kill bacteria, offering a precision approach to treating Enterococcus colonization without disturbing beneficial bacteria. This is different from traditional antibiotics, which can lead to resistance and affect a broader range of bacteria. ^{3 4 6 7 8}

Research Team

Minh-Hong Nguyen, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for healthy adults aged 18-50 with a BMI of 19-40 kg/m2, who are not pregnant, do not have HIV or hepatitis, and agree to avoid other clinical studies. Participants must understand the study and follow its schedule. They should be in good health as determined by medical history and screening tests.

Inclusion Criteria

I agree to use birth control as required.

Good general health as shown by medical history, physical examination, and screening laboratory tests or clinical laboratory abnormalities per clinical judgment of Principal Investigator (PI)

Female subjects must have a negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test at Screening and within 24 hours of initial treatment on Day 1

Exclusion Criteria

I haven't had cancer in the last 5 years, except for skin cancer.

Any other criteria which, in the Investigator's opinion, would compromise the ability of the subject to participate in the study, the safety of the study, or the results of the study

I have not taken certain medications recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Participants receive VRELysin or placebo orally three times a day for 7 days to assess safety in healthy adults

1 week

Daily visits for dosing

Phase 2a Treatment

Participants receive VRELysin or placebo orally three times a day for 14 days to evaluate safety and efficacy in VRE-colonized adults

2 weeks

Daily visits for dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and VRE shedding

up to 180 days

Treatment Details

Interventions

• Placebo
• VRELysin™

Trial Overview The trial is testing VRELysin™ against a placebo in a randomized, double-blind setup to see if it's safe and effective for people colonized by Enterococcus bacteria. It's the first time this treatment is being tried on humans.

Participant Groups

Group I: VRELysin™ Active Control 1 Intervention

Dose is 1mL of bacteriophage preparation given orally three times a day for 7 days (Phase 1) or 14 days (Phase 2a)

Group II: Placebo Placebo Group 1 Intervention

Dose is 1mL of placebo given orally three times a day for 7 days (Phase 1) or 14 days (Phase 2a)

Who Is Running the Clinical Trial?

Intralytix, Inc.

Lead Sponsor

Trials

3

Recruited

160+

Findings from Research

In a study of 526 stool specimens from high-risk hospitalized patients, 19.8% were found to be colonized with vancomycin-resistant enterococci (VRE), highlighting a significant prevalence of VRE in this population.

Routine screening of C difficile-positive stool specimens for VRE was shown to be cost-effective, identifying VRE in 41.4% of patients tested, and costing approximately $62 per VRE-positive patient, suggesting that this strategy is beneficial for controlling VRE transmission in hospitals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory-based surveillance for vancomycin-resistant enterococci: utility of screening stool specimens submitted for Clostridium difficile toxin assay. Leber, AL., Hindler, JF., Kato, EO., et al.[2015]

A novel bacteriophage targeting Enterococcus faecalis was isolated and shown to significantly reduce the metabolic activity of drug-resistant enterococci biofilms from chronic periodontitis patients, achieving a reduction of at least 5 log CFU/ml after 48 hours.

This study suggests that phage therapy could be a promising alternative treatment for infections caused by multidrug-resistant enterococci, although the phage has a narrow host range.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation of a Novel Phage and Targeting Biofilms of Drug-Resistant Oral Enterococci. Bhardwaj, SB., Mehta, M., Sood, S., et al.[2022]

Enterococci and their bacteriophages (phages) play a crucial role in human health, with phages acting as targeted agents to eliminate harmful enterococci in the microbiota or infected tissues.

Given the rise of multidrug-resistant enterococci and the decline in new antibiotic development, enterococcal phages are emerging as promising therapeutic options, potentially revolutionizing treatment strategies against resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular mechanisms of enterococcal-bacteriophage interactions and implications for human health. Canfield, GS., Duerkop, BA.[2021]

A newly isolated virulent bacteriophage, vB_GEC_EfS_9, shows promise for treating infections caused by antibiotic-resistant Enterococcus faecium, which is known for causing serious opportunistic infections.

Phage therapy, like the use of vB_GEC_EfS_9, offers advantages over traditional antibiotics, including a lower likelihood of resistance development and the ability to specifically target harmful bacteria without disrupting beneficial microbiota.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel lytic bacteriophage vB_GEC_EfS_9 against Enterococcus faecium. Rigvava, S., Kusradze, I., Tchgkonia, I., et al.[2022]

A collection of 19 Enterococcus phages was isolated, showing effectiveness in treating antibiotic-resistant Enterococcus faecalis and Enterococcus faecium infections, with some phages being more effective in combinations (cocktails) than alone.

Using phage cocktails not only improved the ability to clear bacterial cultures but also delayed the emergence of phage-resistant mutants, highlighting a promising strategy for phage therapy against antibiotic-resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phage Cocktails Constrain the Growth of Enterococcus. Wandro, S., Ghatbale, P., Attai, H., et al.[2022]

A newly isolated lytic bacteriophage from sewage effectively targets vancomycin-resistant Enterococcus (VREF), which is responsible for serious infections like endocarditis and UTIs, showing promise as an alternative therapy.

The bacteriophage demonstrated optimal activity at 37°C, with a high burst size of 512 viral particles per infected bacterial cell, indicating its potential for effective treatment against VREF infections in various environments, including compost and soil.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of a Lytic Phage SRG1 against Vancomycin-Resistant Enterococcus faecalis in Compost and Soil. Rahmat Ullah, S., Andleeb, S., Raza, T., et al.[2018]

Vancomycin-resistant enterococci (VRE), particularly those with the vanB genotype, pose a growing challenge for treatment, especially in patients with weakened immune systems or those exposed to broad-spectrum antibiotics.

Effective treatment options for vanB enterococci include existing antimicrobials like teicoplanin and daptomycin, as well as new drugs and strategies such as combination therapies and bacteriophages, highlighting the evolving landscape of antimicrobial therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Options for Infections due to vanB Genotype Vancomycin-Resistant Enterococci. Riccardi, N., Monticelli, J., Antonello, RM., et al.[2021]

In a mouse model of severe septic peritonitis, a single injection of a bacteriophage cocktail completely reversed a 100% mortality rate caused by Vancomycin-Resistant Enterococcus faecalis, demonstrating its strong therapeutic efficacy as a rescue treatment.

The study found that combining bacteriophages with a suboptimal antibiotic regimen enhanced treatment success without negatively impacting the microbiome, highlighting the potential for phage therapy to improve outcomes in antibiotic-resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined bacteriophages and antibiotics as an efficient therapy against VRE Enterococcus faecalis in a mouse model. Gelman, D., Beyth, S., Lerer, V., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Laboratory-based surveillance for vancomycin-resistant enterococci: utility of screening stool specimens submitted for Clostridium difficile toxin assay. [2015]

2. India pubmed.ncbi.nlm.nih.gov

Isolation of a Novel Phage and Targeting Biofilms of Drug-Resistant Oral Enterococci. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Molecular mechanisms of enterococcal-bacteriophage interactions and implications for human health. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Novel lytic bacteriophage vB_GEC_EfS_9 against Enterococcus faecium. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Phage Cocktails Constrain the Growth of Enterococcus. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Effectiveness of a Lytic Phage SRG1 against Vancomycin-Resistant Enterococcus faecalis in Compost and Soil. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Therapeutic Options for Infections due to vanB Genotype Vancomycin-Resistant Enterococci. [2021]

8. France pubmed.ncbi.nlm.nih.gov

Combined bacteriophages and antibiotics as an efficient therapy against VRE Enterococcus faecalis in a mouse model. [2019]