VE303 for C. Difficile Infection

(RESTORATiVE303 Trial)

Recruiting at 221 trial locations

Overseen By Steven Shiff, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Vedanta Biosciences, Inc.

Must be taking: Standard antibiotics

Must not be taking: Antidiarrheals, Bezlotoxumab

Disqualifiers: Chronic diarrhea, Celiac, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 14 days

852 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called VE303 for individuals with Clostridioides difficile infections (CDI), which can cause serious diarrhea and gut issues. The goal is to determine if VE303 can safely reduce the recurrence of these infections after standard antibiotic treatment. Participants will take either VE303 or a placebo (a pill with no active medicine) for 14 days. Those who have had CDI before or are at high risk of recurrence, such as individuals with kidney issues or those using certain stomach medicines, may be suitable for the trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must complete a course of standard antibiotic therapy for CDI before starting the study drug. You cannot use antidiarrheal drugs within 3 days before the first dose of the study drug, and you should not expect to take antibiotics for other conditions during the trial.

Is there any evidence suggesting that VE303 is likely to be safe for humans?

Research has shown that VE303 is generally safe for people. In earlier studies, patients who took VE303 experienced few side effects, suggesting safety for most individuals. Made from a mix of natural gut bacteria, VE303 offers a promising option to prevent the recurrence of C. difficile infections. Studies have found that this type of treatment usually doesn't cause serious side effects. While VE303 is still under testing, its safety record so far appears favorable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for C. difficile infections, which typically involves antibiotics like vancomycin or metronidazole, VE303 is unique because it uses a novel approach involving a mix of live bacterial strains. Researchers are excited about VE303 because it aims to restore the healthy balance of gut bacteria after an infection, potentially reducing the risk of recurrence. This method of using beneficial bacteria could offer a more natural and long-term solution compared to traditional antibiotics, which can sometimes disrupt the gut microbiome and lead to further complications.

What evidence suggests that VE303 might be an effective treatment for C. difficile infection?

Research has shown that VE303, a mix of 8 specific bacteria, may help prevent the recurrence of Clostridioides difficile infections (CDI). In this trial, participants in the VE303 arm will take capsules containing VE303. Studies have found that VE303 can significantly reduce the risk of CDI returning in individuals prone to recurrence. One study showed that participants taking VE303 experienced fewer repeat infections compared to those who did not. This suggests that VE303 might help maintain gut health after treating the initial infection with standard antibiotics. The results so far are promising for those with recurrent CDI. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults, especially those over 65 or with kidney issues, who have had Clostridioides difficile infection (CDI) recently or in the past year. It's also for people with weakened immune systems, organ transplant recipients, and regular users of stomach acid reducers. Children over 12 with CDI history can join too.

Inclusion Criteria

I am 12 or older and have had at least two episodes of C. diff infection in the last 6 months.

I am over 75 with CDI or over 12 with CDI and have at least two risk factors like being over 65, kidney issues, regular PPI use, a past CDI episode, immunosuppression, or an organ transplant.

I had a recent severe diarrhea episode treated successfully with antibiotics for C. diff.

Exclusion Criteria

For both Stage 1 and Stage 2: History of chronic diarrhea, Laboratory-confirmed infectious diarrhea other than CDI, Known or suspected toxic megacolon or small bowel ileus, History of confirmed celiac disease, inflammatory bowel disease, microscopic colitis, short gut, GI tract fistulas, or a recent episode of intestinal ischemia or ischemic colitis, Receipt of bezlotoxumab during the course of SoC antibiotic treatment, Receipt of genetically modified live bacterial, fungal, viral, or bacteriophage isolates, fecal-derived live bacterial isolates, or other LBPs for CDI-associated diarrhea within 6 months prior to randomization, Use of antidiarrheal drugs within 3 days prior to the planned first dose of study drug, Anticipated administration of oral or parenteral antibacterial therapy for a non-CDI indication after randomization

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 14-day course of VE303 or placebo after completing 10 to 21 days of standard antibiotic treatment

14 days

Follow-up

Participants are monitored for CDI recurrence and safety until Week 8

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• VE303

Trial Overview The RESTORATiVE303 study tests VE303 against a placebo to see if it prevents CDI from coming back within eight weeks after treatment. Participants will take either VE303 or a placebo for two weeks and be monitored for safety and recurrence.

How Is the Trial Designed?

Group I: VE303 Experimental Treatment 1 Intervention

Subjects assigned to the VE303 arm will take 3 capsules containing VE303 per day for 14 days after completing 10 to 21 days of standard of care antibiotic treatment for the qualifying CDI episode.

Group II: Placebo Placebo Group 1 Intervention

Subjects assigned to the placebo arm will take 3 placebo capsules per day for 14 days after completing 10 to 21 days of standard of care antibiotic treatment for the qualifying CDI episode.

Who Is Running the Clinical Trial?

Vedanta Biosciences, Inc.

Lead Sponsor

Trials

7

Recruited

1,200+

Published Research Related to This Trial

A study of 56 C. difficile strains from various sources identified 11 variant toxinotypes, including five new ones (XVI to XX), highlighting the genetic diversity of this pathogen.

The research revealed that two new groups of strains (toxinotypes XVI and XVII) are A(-)B(+) and differ from known strains, indicating potential implications for understanding the pathogenicity and treatment of C. difficile infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New types of toxin A-negative, toxin B-positive strains among Clostridium difficile isolates from Asia. Rupnik, M., Kato, N., Grabnar, M., et al.[2022]

Clostridium difficile infection is the leading cause of infectious diarrhea in hospitalized patients, surpassing MRSA as a top hospital-acquired infection, with a high recurrence rate of 20-25% after initial treatment.

Due to the limitations of traditional treatments like metronidazole and vancomycin, there is growing interest in alternative strategies that target C. difficile spores, restore gut flora, and enhance the immune response to reduce recurrence and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of alternative or adjuvant pharmacologic treatment strategies in the prevention and treatment of Clostridium difficile infection. Musgrave, CR., Bookstaver, PB., Sutton, SS., et al.[2021]

Clostridium difficile-associated disease (CDAD) can range from mild diarrhea to severe conditions like pseudomembranous colitis, with a significant financial impact on healthcare systems, costing up to $1.1 billion per year in the USA alone.

The emergence of more virulent strains, particularly PCR ribotype 027, has led to increased rates of CDAD with higher mortality and complications, highlighting the need for improved surveillance and control measures in healthcare settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emergence of Clostridium difficile-associated disease in North America and Europe. Kuijper, EJ., Coignard, B., Tüll, P.[2022]

In a mouse model of Clostridium difficile infection (CDI), mice developed protective immunity after infection, generating both systemic and mucosal antibodies that helped prevent CDI upon rechallenge.

The study found that even immunodeficient mice could develop protective immunity through mucosal IgA antibodies, indicating that multiple mechanisms can contribute to protection against CDI, depending on the host's immune status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protection from Clostridium difficile infection in CD4 T Cell- and polymeric immunoglobulin receptor-deficient mice. Johnston, PF., Gerding, DN., Knight, KL.[2021]

In a study of 893 hospitalized patients with Clostridium difficile infection (CDI), 10.97% died within 30 days, highlighting the serious nature of this infection.

Key predictors of 30-day mortality included advanced age, the Charlson comorbidity index, ICU status, and peptic ulcer disease, while acid suppression treatment did not significantly affect mortality rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of 30-Day Mortality in Hospitalized Patients with Clostridium difficile Infection. Chintanaboina, J., Navabi, S., Suchniak-Mussari, K., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37060545/

VE303, a Defined Bacterial Consortium, for Prevention of ... To determine the efficacy of VE303, a defined bacterial consortium of 8 strains of commensal Clostridia, in adults at high risk for CDI recurrence.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03788434

Phase 2 Study of VE303 for Prevention of Recurrent ... This study evaluated the safety and efficacy of VE303 for participants with primary C. difficile infection (pCDI) at high risk for recurrence or subjects with ...

3. vedantabio.com vedantabio.com/commitment-to-patients/restorative303/

RESTORATiVE303 RESTORATiVE303 is a double-blind, placebo-controlled, Phase 3 study to evaluate the safety and efficacy of a 14-day course of VE303.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10105904/

VE303, a Defined Bacterial Consortium, for Prevention of ... To determine the efficacy of VE303, a defined bacterial consortium of 8 strains of commensal Clostridia, in adults at high risk for CDI recurrence.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06237452

VE303 for Prevention of Recurrent Clostridioides Difficile ... The overall objective of the RESTORATiVE303 study is to evaluate the safety and the Clostridioides difficile infection (CDI) recurrence rate at Week 8 in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10678313/

Results from the Phase 2 CONSORTIUM Study After completion of antibiotic treatment for a lab-confirmed CDI episode, 79 subjects were randomized to low-dose VE303, high-dose VE303, or ...