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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new oral treatment called VRELysin, which uses bacteriophages (viruses that target bacteria) to combat Enterococcus bacteria in the gut. Researchers aim to determine if this treatment is safe and effective for individuals who are either healthy or already have these bacteria in their system. Participants should have previously tested positive for Enterococcus bacteria in their stool. The trial involves taking a liquid dose three times a day, either the active treatment or a placebo (a dummy treatment with no active ingredients), for one to two weeks. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that phage therapy, such as VRELysin, could effectively treat bacterial infections. However, the researchers are still gathering safety information about VRELysin in humans. This trial marks the first time VRELysin is tested in people, so only early safety results are available. As an early-phase trial, researchers closely monitor VRELysin for any side effects.

Generally, studies of similar treatments suggest that phage therapy is safe. Other phage therapies have reported only minor side effects, but more will be known about VRELysin's safety after this trial. Early-phase trials focus heavily on safety, so participants receive careful monitoring for any problems. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike traditional treatments for Enterococcus colonization, which often rely on antibiotics, VRELysin™ is unique because it uses bacteriophages—viruses that specifically target and destroy bacteria. This novel mechanism of action offers a targeted approach that can reduce bacterial resistance, a significant issue with current antibiotic treatments. Researchers are excited about VRELysin™ because it provides a potential alternative to antibiotics, with the ability to selectively eliminate harmful bacteria without disrupting the beneficial microbial balance in the body. Additionally, this oral treatment is easy to administer and could offer quicker results, improving patient outcomes and reducing the spread of drug-resistant bacteria.

What evidence suggests that VRELysin™ might be an effective treatment for Enterococcus colonization?

Research has shown that phage therapy, such as VRELysin, uses viruses to target and kill specific bacteria, including Enterococcus. In this trial, some participants will receive VRELysin, which initial findings suggest may help reduce Enterococcus colonization by specifically attacking these bacteria in the gut. Phages, as a natural enemy of bacteria, can be a powerful tool in managing bacterial growth. Early indicators point to VRELysin's potential in managing Vancomycin-Resistant Enterococci (VRE), a type of bacteria resistant to many antibiotics. Although human data is still emerging, the mechanism of phage therapy offers hope for its effectiveness. ^{2 3 4 6 7}

Who Is on the Research Team?

Minh-Hong Nguyen, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

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

Pregnant or breastfeeding

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05715619

Study Details | NCT05715619 | Safety and Efficacy of Oral ... The purpose of this study is to determine if VRELysin is safe and effective in adults in a continuous Phase 1/2a trial. Phase 1 will asses the safety of ...

2. withpower.com withpower.com/trial/phase-2-vancomycin-resistant-enterococcal-colonization-3-2023-547cd

Oral Phage Therapy for Enterococcus Colonization What data supports the effectiveness of the treatment VRELysin™ for Enterococcus colonization? Research shows that phage therapy, which uses viruses to ...

3. synapse.patsnap.com synapse.patsnap.com/drug/4d9d0d4d49c842bc9d95ade05260073f

VRELysin - Drug Targets, Indications, Patents A Phase 1/2a Double-Blind, Randomized, Placebo-Controlled Trial to Assess the Safety and Efficacy of Oral Administration of the Phage Cocktail, VRELysin™, ...

4. intralytix.com intralytix.com/article/115?e=Intralytix-Launches-Phase-1%2F2a-Phage-Therapy-Trial-of-Its-VRELysin%26trade%3B-Phage-Preparation%2C-to-Assess-Safety-and-Efficacy-in-Healthy-and-VRE-Colonized-Subjects

Intralytix Launches Phase 1/2a Phage Therapy Trial of Its ... VRELysin offers a potentially very powerful new tool for clinicians to manage VRE colonization in the patients. While VRE infections are not ...

5. medjrf.com medjrf.com/0869-2106/article/download/678618/202884

Review of Alternative Antimicrobial Therapies SYN-004 protects the gut microbiota from disruption by reducing the harmful effects of recurrent. C. difficile infection, limiting colonization by opportunistic.

6. intralytix.com intralytix.com/clinicaltrials/VRELysin

VRELysin Intralytix, Inc.'s VRELysin™ bacteriophage therapy targeting vancomycin resistant Enterococci colonization in the gastrointestinal tract has entered a Phase ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9324367/

Phage Products for Fighting Antimicrobial Resistance - PMC Researchers found great potential for phage therapy and phage therapies are increasingly being used for human bacterial diseases.