VE303 for C. Difficile Infection

(RESTORATiVE303 Trial)

Recruiting at 160 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

Trial Summary

What is the purpose of this trial?

The overall objective of the RESTORATiVE303 study is to evaluate the safety and the Clostridioides difficile infection (CDI) recurrence rate at Week 8 in participants who receive a 14-day course of VE303 or matching placebo. The objectives and endpoints are identical for Stage 1 (recurrent CDI) and Stage 2 (high-risk primary CDI).

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.

What makes the drug VE303 unique for treating C. difficile infection?

VE303 is unique because it is a microbiome-based treatment designed to restore the natural balance of gut bacteria, which can help prevent the recurrence of C. difficile infections, unlike traditional antibiotics that may disrupt gut flora. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

New types of toxin A-negative, toxin B-positive strains among Clostridium difficile isolates from Asia. [2022]

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

Protection from Clostridium difficile infection in CD4 T Cell- and polymeric immunoglobulin receptor-deficient mice. [2021]

3. Canada pubmed.ncbi.nlm.nih.gov

Use of alternative or adjuvant pharmacologic treatment strategies in the prevention and treatment of Clostridium difficile infection. [2021]

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

Predictors of 30-Day Mortality in Hospitalized Patients with Clostridium difficile Infection. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Emergence of Clostridium difficile-associated disease in North America and Europe. [2022]