REC-3964 for C. difficile Infection

(ALDER Trial)

Recruiting at 12 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Recursion Pharmaceuticals Inc.

Must be taking: Vancomycin

Disqualifiers: Active chronic diarrheal illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

3 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are taking medications for chronic diarrheal illnesses like ulcerative colitis or Crohn's disease, they must be controlled to participate.

What data supports the effectiveness of the drug REC-3964 for C. difficile Infection?

The research on bezlotoxumab, a drug used for recurrent C. difficile infections, shows it significantly reduces recurrence compared to a placebo, which suggests that similar treatments might be effective. Additionally, novel biomarkers and PCR cycle thresholds have been identified as important predictors for recurrence, indicating that understanding these factors can help in optimizing treatment strategies. ^{1 2 3 4 5}

What is the purpose of this trial?

This is a multi-center, open-label study to investigate the safety, tolerability, pharmacokinetics (PK) and efficacy of RE-3964 (doses of either 250 mg or 500 mg PO every 12 hours) for the reduction of Clostridioides difficile infection (CDI).

Eligibility Criteria

This trial is for adults over 18 who have had diarrhea due to Clostridioides difficile infection (CDI), confirmed by a stool test, and were treated with vancomycin. Participants should be at high risk of the infection coming back after treatment and must join within two days of finishing their vancomycin course.

Inclusion Criteria

I am over 18, had C. difficile diarrhea, tested positive, and was treated with vancomycin.

I am at high risk for recurring C. difficile infection and can be treated with vancomycin.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive REC-3964 (250 mg or 500 mg) or undergo observation for 28 days

4 weeks

Daily dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extended Follow-up

Participants are monitored for recurrent Clostridioides difficile infection (rCDI) and adverse events

8 weeks

Treatment Details

Interventions

• REC-3964

Trial Overview The study tests REC-3964, given orally in doses of either 250 mg or 500 mg every 12 hours, to see if it's safe and effective in reducing CDI symptoms. It's an open-label trial conducted across multiple centers where everyone knows what treatment they're getting.

Participant Groups

Group I: REC-3964 Low-dose Experimental Treatment 1 Intervention

Participants will receive 250 mg REC-3964 q12h REC-3964 250 mg capsules

Group II: REC-3964 High-dose Experimental Treatment 1 Intervention

Participants will receive 500 mg REC-3964 q12h REC-3964 250 mg capsules

Group III: Observation Active Control 1 Intervention

Participants will undergo watchful waiting

Who Is Running the Clinical Trial?

Recursion Pharmaceuticals Inc.

Lead Sponsor

Trials

6

Recruited

450+

Findings from Research

In a pooled analysis of the MODIFY I and II trials involving patients with recurrent Clostridium difficile infection (rCDI), bezlotoxumab treatment was associated with a reduction in cumulative inpatient-days, averaging 12.1 days compared to 14.1 days for the placebo group over an 84-day follow-up period.

The reduction in inpatient-days was more pronounced in patients with multiple risk factors for rCDI, indicating that bezlotoxumab may significantly decrease healthcare resource use for those at higher risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bezlotoxumab Is Associated With a Reduction in Cumulative Inpatient-Days: Analysis of the Hospitalization Data From the MODIFY I and II Clinical Trials. Basu, A., Prabhu, VS., Dorr, MB., et al.[2022]

In a study of 210 Clostridioides difficile infection (CDI) episodes treated at a tertiary care hospital, metronidazole was effective for uncomplicated cases, showing a 20% recurrence rate after the first treatment, but had limitations in severe cases.

The 60-day mortality rate was 17%, indicating that CDI is a serious condition, especially in patients with multiple risk factors or severe indicators, suggesting that alternative treatments like oral vancomycin or fidaxomicin may be more appropriate for these high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of Clostridioides difficile infections treated in a Swiss tertiary care hospital: an observational study. Haubitz, S., Bartlomé, N., Bucheli Laffer, E., et al.[2021]

A study involving 257 hospitalized patients identified key biomarkers, including interleukin 6 (IL-6) and PCR cycle threshold (CT), that can accurately predict the risk of recurrent Clostridioides difficile infection, achieving an accuracy of 0.88.

The research suggests that using these biomarkers, especially PCR CT, can enhance current clinical models and help in better risk stratification, potentially improving the use of effective therapies like fecal transplants and bezlotoxumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Biomarkers, Including tcdB PCR Cycle Threshold, for Predicting Recurrent Clostridioides difficile Infection. Madden, GR., Rigo, I., Boone, R., et al.[2023]

The ATLAS score was not effective in predicting 90-day recurrence of Clostridium difficile infections, but it was useful in predicting disease complications and one-year all-cause mortality in a study of 144 patients.

Serum albumin levels were identified as a significant predictor for 90-day recurrence, with specific thresholds indicating risk, highlighting its importance in managing treatment for C. difficile infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoalbuminemia as predictor of recurrence of Clostridium difficile infection. Knafl, D., Vossen, MG., Gerges, C., et al.[2020]

A new risk prediction model developed from a study of 401 patients with Clostridium difficile infection (CDI) identified key predictors of 30-day mortality, including malignancy, elevated serum creatinine, high BUN-to-creatinine ratio, and increased glucose levels, showing a 23.4% mortality rate within 30 days.

This model outperformed existing guidelines in predicting both 30-day mortality and prolonged ICU stays, indicating that incorporating specific biochemical markers can enhance clinical decision-making for patients with CDI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk prediction for 30-day mortality among patients with Clostridium difficile infections: a retrospective cohort study. Chiang, HY., Huang, HC., Chung, CW., et al.[2023]

References

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

Bezlotoxumab Is Associated With a Reduction in Cumulative Inpatient-Days: Analysis of the Hospitalization Data From the MODIFY I and II Clinical Trials. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Outcome of Clostridioides difficile infections treated in a Swiss tertiary care hospital: an observational study. [2021]

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

Novel Biomarkers, Including tcdB PCR Cycle Threshold, for Predicting Recurrent Clostridioides difficile Infection. [2023]

4. Austria pubmed.ncbi.nlm.nih.gov

Hypoalbuminemia as predictor of recurrence of Clostridium difficile infection. [2020]

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

Risk prediction for 30-day mortality among patients with Clostridium difficile infections: a retrospective cohort study. [2023]