LMN-201 for C. Difficile Infection

Recruiting at 17 trial locations

Overseen By Asa Davis

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Lumen Bioscience, Inc.

Must be taking: SOC antibiotics

Must not be taking: Mu-agonist opioids, Anticholinergics

Disqualifiers: Fulminant colitis, ICU admission, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

375 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multisite study to evaluate the safety, tolerability, and efficacy of LMN-201 in participants recently diagnosed with CDI who are scheduled to receive or are receiving SOC antibiotic therapy against C. difficile.

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 can continue taking antibiotics for infections not related to the gut. If you're on certain treatments like mu-agonist opioids, you may need to be on a stable dose without increasing it during the study.

What safety data exists for LMN-201 or similar treatments?

The research articles provided do not contain any relevant safety information for LMN-201 or similar treatments for C. Difficile Infection. ^{1 2 3 4 5}

How does the drug LMN-201 differ from other treatments for C. difficile infection?

LMN-201, also known as LFF571, is unique because it specifically targets the prokaryotic translation elongation factor Tu, which is different from other antibiotics used for C. difficile. It is taken orally and has high concentrations in the gut, which is where the infection occurs, while having minimal presence in the bloodstream, potentially reducing systemic side effects. ^{6 7 8 9 10}

Eligibility Criteria

Adults diagnosed with C. difficile infection (CDI) who are having frequent watery bowel movements and have tested positive for the toxin B. They must be starting or on a standard antibiotic treatment for CDI, able to take oral medication, willing to follow the study plan, and use effective contraception if of reproductive potential.

Inclusion Criteria

I am 18 years old or older.

Provision of signed and dated informed consent form

I am scheduled for a short-term antibiotic treatment for C. diff infection.

Exclusion Criteria

Pregnancy, anticipated pregnancy, or breastfeeding

I cannot swallow pills that need to reach my intestines.

Psychiatric illness that would affect compliance with medications, study capsules, or follow-up

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LMN-201 or placebo in conjunction with SOC antibiotic therapy

8 weeks

Observation

Participants are monitored for CDI recurrence and global cure

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• LMN-201
• Placebo

Trial Overview The trial is testing LMN-201's ability to prevent CDI from coming back in patients currently treated with standard antibiotics. Participants will either receive LMN-201 or a placebo without knowing which one they get.

Participant Groups

Group I: Sentinel Cohort Experimental Treatment 1 Intervention

Group II: LMN-201 Active Control 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Lumen Bioscience, Inc.

Lead Sponsor

Trials

7

Recruited

1,700+

Congressionally Directed Medical Research Programs

Collaborator

Trials

59

Recruited

10,600+

Findings from Research

In a double-blind crossover study involving 21 patients with chronic diarrhea, loperamide was found to be significantly more effective than placebo in controlling symptoms, with a median daily dose of 6 mg leading to fewer and heavier stools.

Patients reported a preference for loperamide over placebo, and the treatment had few gastrointestinal side effects, indicating it is a safe and effective option for managing chronic diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind placebo-controlled study of loperamide (Imodium) in chronic diarrhoea caused by ileocolic disease or resection. Mainguet, P., Fiasse, R.[2019]

Silodosin significantly improves lower urinary tract symptoms in men with benign prostatic hyperplasia, as evidenced by a 2.7 point reduction in the International Prostate Symptom Score (IPSS) compared to placebo, based on a pooled analysis of 1494 patients from three 12-week trials.

The most common side effect of silodosin is ejaculatory dysfunction, affecting 22% of patients, while rates of dizziness and orthostatic hypotension were similar to those in the placebo group, indicating a relatively safe profile for cardiovascular effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pooled analysis of individual patient data from registrational trials of silodosin in the treatment of non-neurogenic male lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). Novara, G., Chapple, CR., Montorsi, F.[2014]

Lactulose has been shown to provide a generally beneficial response in treating constipation compared to a placebo, although the improvement may be only marginal in some cases.

The review included various patient populations, including geriatric and terminally ill patients, but often did not consider dietary techniques that could also aid in improving bowel movements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactulose in the management of constipation: a current review. Kot, TV., Pettit-Young, NA.[2017]

A meta-analysis of 34 studies found that the placebo effect from nutritional supplements like caffeine and extracellular buffers is very small, with a median effect size of 0.09, indicating only a slight improvement in performance compared to control.

The placebo effect accounted for a significant portion of the overall intervention effect, contributing 25% for buffers and 59% for caffeine, suggesting that psychological factors may play a substantial role in the perceived benefits of these supplements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonplacebo Controls to Determine the Magnitude of Ergogenic Interventions: A Systematic Review and Meta-analysis. Marticorena, FM., Carvalho, A., Oliveira, LF., et al.[2023]

In a study involving 14 patients with chronic diarrhea, loperamide was significantly more effective than both placebo and lidamidine in controlling stool consistency.

The study used a double-blind crossover design, and while many patients withdrew early from placebo and lidamidine due to lack of control over diarrhea, only one patient withdrew during loperamide treatment, highlighting its superior efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind crossover comparison of lidamidine, loperamide and placebo for the control of chronic diarrhoea. Allison, MC., Sercombe, J., Pounder, RE.[2019]

LFF571, a novel drug targeting Clostridium difficile, was found to be safe and well tolerated in a study involving 56 healthy subjects, with no serious adverse events reported.

The drug showed limited systemic exposure but achieved high concentrations in feces, indicating its potential effectiveness for treating C. difficile infections while minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A first-in-human, randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study to assess the safety and tolerability of LFF571 in healthy volunteers. Ting, LS., Praestgaard, J., Grunenberg, N., et al.[2023]

In a Phase IV clinical trial involving 24 patients with chemotherapy-induced febrile neutropenia, filgrastim significantly accelerated recovery from neutropenia and fever, with a median recovery time of just two days.

The use of filgrastim also led to a reduction in hospital stay and intravenous antibiotic usage, demonstrating its efficacy and safety, as only mild adverse events were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granulocyte colony-stimulating factor (filgrastim) in chemotherapy-induced febrile neutropenia. Advani, SH., Achreckar, S., Thomas, D., et al.[2021]

In a clinical trial involving 54 patients with metastatic colorectal cancer, low-molecular-weight fucoidan (LMF) significantly improved the disease control rate (DCR) to 92.8% compared to 69.2% in the control group, suggesting its potential as an effective supplemental therapy.

While LMF enhanced disease control, it did not show significant differences in overall survival, progression-free survival, overall response rate, adverse effects, or quality of life compared to the control group, indicating that its primary benefit may lie in improving disease management rather than overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Low-Molecular-Weight Fucoidan as a Supplemental Therapy in Metastatic Colorectal Cancer Patients: A Double-Blind Randomized Controlled Trial. Tsai, HL., Tai, CJ., Huang, CW., et al.[2021]

The FOLFIRI regimen, which combines irinotecan (CPT-11) with 5-fluorouracil (5-FU) and Leucovorin (LV), has been established as a standard first-line chemotherapy for metastatic colorectal cancer since 2000, based on results from controlled randomized phase III trials.

This regimen requires careful supportive therapy to ensure safe administration, highlighting the importance of managing side effects while maximizing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[FOLFIRI regimen for metastatic or recurrent colorectal cancer]. Uemura, N., Yamada, Y.[2013]

In a phase III trial involving 876 patients with stage II and III colon cancer, both levogyre (L) and dextro-levogyre (DL) forms of leucovorin showed similar safety profiles, with no significant difference in grade 3/4 toxicity rates (20% for L-LV vs. 17% for DL-LV).

There were no statistically significant differences in disease-free survival (66.7% for L-LV vs. 67.2% for DL-LV) or overall survival (78.2% for L-LV vs. 74.5% for DL-LV) after a median follow-up of 6.1 years, indicating that both forms of leucovorin are equally effective when used with 5-fluorouracil for treating colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the levogyre and dextro-levogyre forms of leucovorin in a phase III trial of bimonthly LV5FU2 versus monthly 5-fluorouracil and high-dose leucovorin for patients with stage II and III colon cancer (GERCOR C96.1). Baumgaertner, I., Quinaux, E., Khalil, A., et al.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Double-blind placebo-controlled study of loperamide (Imodium) in chronic diarrhoea caused by ileocolic disease or resection. [2019]

2. England pubmed.ncbi.nlm.nih.gov

A pooled analysis of individual patient data from registrational trials of silodosin in the treatment of non-neurogenic male lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). [2014]

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

Lactulose in the management of constipation: a current review. [2017]

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

Nonplacebo Controls to Determine the Magnitude of Ergogenic Interventions: A Systematic Review and Meta-analysis. [2023]

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

A double-blind crossover comparison of lidamidine, loperamide and placebo for the control of chronic diarrhoea. [2019]

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

A first-in-human, randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study to assess the safety and tolerability of LFF571 in healthy volunteers. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Granulocyte colony-stimulating factor (filgrastim) in chemotherapy-induced febrile neutropenia. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of Low-Molecular-Weight Fucoidan as a Supplemental Therapy in Metastatic Colorectal Cancer Patients: A Double-Blind Randomized Controlled Trial. [2021]

9. Japan pubmed.ncbi.nlm.nih.gov

[FOLFIRI regimen for metastatic or recurrent colorectal cancer]. [2013]

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

Comparison of the levogyre and dextro-levogyre forms of leucovorin in a phase III trial of bimonthly LV5FU2 versus monthly 5-fluorouracil and high-dose leucovorin for patients with stage II and III colon cancer (GERCOR C96.1). [2013]