REC-3964 for C. difficile Infection

(ALDER Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment called REC-3964 for people with C. difficile infection (CDI), a condition that causes severe diarrhea. Participants will receive either a high or low dose of the medication, or they will be observed without intervention. The trial targets individuals who have recently recovered from a CDI episode after taking vancomycin and are at high risk of recurrence. Those who have tested positive for C. difficile toxins and whose symptoms have improved with treatment might find this trial suitable. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important medical advancements.

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.

Is there any evidence suggesting that REC-3964 is likely to be safe for humans?

Research has shown that REC-3964 is well tolerated by healthy volunteers. In earlier studies, no serious side effects were reported. This suggests the treatment might be safe for people. However, it is important to remember that safety information is still being collected, as the treatment is currently in phase 2 trials. This phase aims to gather more information about how people handle the treatment and its effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for C. difficile infection?

Unlike the standard treatments for C. difficile infection, which typically include antibiotics like vancomycin and metronidazole, REC-3964 offers a novel approach. Researchers are excited about REC-3964 because it targets the infection differently, potentially reducing recurrence rates, which is a common issue with current therapies. Additionally, the dosage flexibility with both high-dose and low-dose options could allow for tailored treatment plans, possibly enhancing effectiveness and minimizing side effects. This innovative angle in tackling C. difficile is what makes REC-3964 stand out from existing options.

What evidence suggests that this trial's treatments could be effective for C. difficile infection?

Research shows that REC-3964 could help treat Clostridioides difficile infection (CDI). Early results suggest that this treatment might lower infection rates. In this trial, participants will receive either a high-dose or low-dose of REC-3964, or they will be in an observation group. Current antibiotics for C. diff often fail to prevent recurrence, with about 20-30% of cases returning. REC-3964 aims to address this issue by potentially offering a more effective solution. It targets the infection while minimizing disruption to healthy gut bacteria, a common problem with current treatments. This could make it a valuable option for patients facing recurring CDI. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06536465

NCT06536465 | The Clostridioides Difficile Trial of REC-3964 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 ...

2. ir.recursion.com ir.recursion.com/news-releases/news-release-details/recursion-announces-first-patient-dosed-phase-2-clinical-study

Recursion announces first patient dosed in Phase 2 clinical ... The purpose of this study is to investigate the safety, tolerability, pharmacokinetics (PK) and efficacy of REC-3964 for the reduction of ...

3. ctv.veeva.com ctv.veeva.com/study/the-clostridioides-difficile-trial-of-rec3964

The Clostridioides Difficile Trial of REC-3964 (ALDER) 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 ...

4. withpower.com withpower.com/trial/phase-2-clostridium-infections-9-2024-64908

REC-3964 for C. difficile Infection (ALDER Trial) The 60-day mortality rate was 17%, indicating that CDI is a serious condition, especially in patients with multiple risk factors or severe indicators, ...

5. synapse.patsnap.com synapse.patsnap.com/article/recursion-doses-first-patient-in-phase-2-trial-of-rec-3964-for-recurrent-c-difficile-infection

Recursion doses first patient in Phase 2 trial of REC-3964 ... Standard antibiotic treatments for C. diff disrupt the gut microbiome and often fail to prevent recurrence. About 20-30% of primary C. diff ...

6. ir.recursion.com ir.recursion.com/news-releases/news-release-details/recursion-announces-completion-phase-1-study-rec-3964

Recursion Announces Completion of Phase 1 Study for ... REC-3964 has been well tolerated in healthy volunteers with no reported serious adverse events. Recursion to explore initiating a Phase 2 ...

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06536465/the-clostridioides-difficile-trial-of-rec-3964

The Clostridioides Difficile Trial of REC-3964 This is a multi-center, open-label study to investigate the safety, tolerability, pharmacokinetics (PK) and efficacy of RE-3964 (doses of ...

8. thelancet.com thelancet.com/journals/ebiom/article/PIIS2352-3964(24)00280-9/fulltext

Predicting Clostridioides difficile infection outcomes with ... Clostridioides difficile infection results in life-threatening short-term outcomes and the potential for subsequent recurrent infection. Predicting these ...