SER-155 for Diarrhea

Recruiting at6 trial locations

Overseen by David Faleck, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Steroids, Infliximab, Vedolizumab, Ustekinumab

Disqualifiers: Active GI infection, Inflammatory bowel disease, Severe neutropenia, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out whether SER-155 may be a safe first treatment that causes few or mild side effects for people due to irEC.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain immunosuppressive therapies or investigational medications for diarrhea/colitis within 30 days before joining the trial.

What data supports the effectiveness of the drug SER-155 for treating diarrhea?

The somatostatin analogue SMS 201-995 has been shown to effectively reduce severe diarrhea in both infants and adults with different underlying conditions, suggesting potential effectiveness for similar treatments like SER-155. ^{1 2 3 4 5}

Is SER-155 safe for human use?

The safety data for cilansetron, a similar drug to SER-155, shows it is generally well tolerated, with constipation being the most common side effect. Rare cases of ischemic colitis (a condition where part of the colon is injured due to reduced blood flow) have been reported, but these resolved without serious issues. ^{6 7 8 9 10}

How does the drug SER-155 differ from other treatments for diarrhea?

SER-155 is unique because it may involve a novel mechanism or combination of components not detailed in the available research, unlike existing treatments like ondansetron, which targets serotonin receptors to reduce diarrhea symptoms. ^{1 6 11 12 13}

Research Team

David Faleck, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults over 18 who've had immunotherapy in the last 6 months can join this trial if they have moderate diarrhea likely caused by the treatment. They must be able to take pills, agree to use birth control for a month after the study, and sign a consent form. People with active gut infections, high steroid doses for other side effects, recent experimental diarrhea treatments, hospitalization for gut issues or severe immune system problems can't participate.

Inclusion Criteria

I am older than 18 years.

I have received immunotherapy in the last 6 months.

I am currently receiving chemotherapy or other cancer treatments.

Exclusion Criteria

I do not have an active infection in my digestive system.

I am taking more than 10 mg of prednisone daily for a non-GI side effect.

I haven't taken experimental diarrhea or gut health drugs in the last 30 days.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SER-155 for the treatment of immunotherapy-related enterocolitis

6 weeks

Visits at day 15 and day 43

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• SER-155 (Probiotic)

Trial Overview The trial is testing SER-155 as a potential first-line treatment for diarrhea resulting from immune checkpoint inhibitor therapy (irEC). The goal is to determine its safety and whether it causes only mild or few side effects in patients suffering from irEC.

Participant Groups

Group I: Participants with Immune checkpoint inhibitor-related enterocolitis (irEC) Experimental Treatment 1 Intervention

Participants with grade 2-3 diarrhea from irEC who have not yet received immunosuppressive therapy for irEC

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Lisa M. DeAngelis

Memorial Sloan Kettering Cancer Center

Chief Medical Officer since 2021

MD from Columbia University

Selwyn M. Vickers

Memorial Sloan Kettering Cancer Center

Chief Executive Officer since 2022

MD from Johns Hopkins University

Findings from Research

In a case study of an infant with severe refractory secretory diarrhea of uncertain cause, the somatostatin analogue SMS 201-995 significantly reduced stool output from 250 ml/kg/day to 80-100 ml/kg/day, demonstrating its efficacy in managing this condition.

The treatment with SMS 201-995 was well-tolerated over 9 months, with no observed metabolic, hormonal, or growth abnormalities, indicating its safety for use in this young patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of idiopathic secretory diarrhea of infancy with the somatostatin analogue SMS 201-995. Jaros, W., Biller, J., Greer, S., et al.[2019]

In a case study of a patient with acute postoperative secretory diarrhea following bowel obstruction, the somatostatin analogue SMS 201-995 significantly reduced colostomy output and normalized intestinal abnormalities, indicating its efficacy in managing this condition.

The patient's diarrhea was linked to abnormal secretion in the small intestine, and SMS 201-995 effectively addressed this issue, suggesting it could be a valuable treatment for similar postoperative complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe posthemicolectomy diarrhea: evaluation and treatment with SMS 201-995. Sharkey, MF., Kadden, ML., Stabile, BE.[2019]

In a study of 29 patients with chemotherapy-induced diarrhea (CID), monthly injections of long-acting octreotide (30 mg) led to a significant reduction in diarrhea severity for 41% of participants who completed the study, allowing them to continue chemotherapy at full doses.

While octreotide showed promise in managing CID, further research is needed to determine its optimal dosage and effectiveness when used alongside other antidiarrheal treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting octreotide as secondary prevention of chemotherapy-induced diarrhea: proof of concept. VAN DEN Heuvel, B., Peeters, M., Hendlisz, A., et al.[2019]

5-aminosalicylic acid (5-ASA) was found to be significantly more effective than placebo in treating active ulcerative colitis, with a pooled odds ratio of 0.39 indicating a lower failure rate in achieving clinical improvement or remission.

While 5-ASA showed better tolerability compared to sulfasalazine (SASP) in active disease, there was insufficient evidence to confirm its superiority over SASP for maintenance therapy, with a pooled odds ratio of 1.29 indicating a higher failure rate to maintain remission compared to SASP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternatives to Sulfasalazine: A Meta-analysis of 5-ASA in the Treatment of Ulcerative Colitis. Sutherland, LR., Roth, DE., Beck, PL.[2018]

In a study of 30 patients with distal ulcerative colitis, those treated with 5-aminosalicylic acid (5-ASA) suppositories had a significantly higher remission rate of 92% after one year compared to only 21% in the placebo group.

The treatment was found to be safe, with no side effects reported, indicating that 5-ASA is an effective option for maintaining remission in patients with distal ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Aminosalicylic acid suppositories in the maintenance of remission in idiopathic proctitis or proctosigmoiditis: a double-blind placebo-controlled clinical trial. D'Arienzo, A., Panarese, A., D'Armiento, FP., et al.[2013]

The 5-HT3-receptor antagonist KB-R6933 effectively inhibited diarrhea induced by serotonin (5-HT) in mice, suggesting its potential as a treatment for certain types of diarrhea.

KB-R6933 also reduced intestinal fluid secretion stimulated by cholera toxin in rats, indicating its broader therapeutic potential in managing diarrhea-related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the 5-hydroxytryptamine3 (5-HT3)-receptor antagonist KB-R6933 on experimental diarrhea models. Ozaki, A., Yoshidomi, M., Sukamoto, T.[2022]

In a study of 409 female patients with irritable bowel syndrome with diarrhea (IBS-D), a dose of 2.5 μg of ramosetron significantly improved abdominal pain and discomfort over three months compared to placebo.

While ramosetron was effective in reducing IBS symptoms, it also caused more constipation than placebo, indicating a need to balance efficacy with potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal dose of ramosetron in female patients with irritable bowel syndrome with diarrhea: A randomized, placebo-controlled phase II study. Fukudo, S., Matsueda, K., Haruma, K., et al.[2018]

Cilansetron, a new medication for irritable bowel syndrome (IBS) with diarrhea, has shown significant efficacy in relieving symptoms in both male and female patients during phase III trials.

The drug is generally well tolerated, with the most common side effect being constipation in 3-12% of patients, and while there have been some cases of ischemic colitis, these were self-limited and did not require surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilansetron. Olden, KW., Crowell, MD.[2017]

Cilansetron, a 5-HT3 receptor antagonist, has shown effectiveness in improving symptoms of irritable bowel syndrome with diarrhea predominance (IBS-D) in both male and female patients, outperforming placebo in two large Phase III clinical trials.

While cilansetron is generally well tolerated, it has a rare but concerning side effect of suspected ischemic colitis, occurring at a rate of 3.77 per 1000 person-years, which is higher than expected in the IBS population. All reported cases have resolved without serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilansetron: a new serotonergic agent for the irritable bowel syndrome with diarrhoea. Chey, WD., Cash, BD.[2019]

Cilansetron, a 5-HT3 receptor antagonist, has shown significant efficacy in treating diarrhea-predominant irritable bowel syndrome (IBS), with two large trials demonstrating superior symptom relief compared to placebo over 3 and 6 months.

While cilansetron can induce constipation in some patients, serious adverse effects were rare, with only four cases of transient ischemic colitis reported among 1484 participants, indicating a generally favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilansetron in the treatment of diarrhea-predominant irritable bowel syndrome? Stacher, G.[2012]

Intraperitoneal administration of L-5-hydroxytryptophan (L-5-HTP) in mice significantly increases defecation, indicating its potential role in inducing diarrhea, particularly in conditions like carcinoid syndrome.

The effectiveness of L-5-HTP in causing diarrhea is dependent on its conversion to serotonin (5-HT), and specific 5-HT antagonists, especially 5-HT3 type, can effectively reduce this diarrhea, suggesting a targeted approach for managing symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-HTP induced diarrhea as a carcinoid syndrome model in mice? Bourin, M., Hascoet, M., Deguiral, P.[2019]

In a study of 15 patients with chemotherapy-induced diarrhoea, acetorphan significantly reduced the average number of stools per day from 6.3 to 4.9, indicating its potential efficacy in managing this side effect of chemotherapy.

Acetorphan also decreased the number of days with liquid stools from 4.7 to 2.4, suggesting it may help alleviate severe diarrhoea without causing constipation, warranting further investigation in a randomized controlled trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of acute chemically induced diarrhea by inhibition of enkephalinase. Results of a pilot study]. Dorval, ED., Regimbeau, C., Gamelin, E., et al.[2013]

In a study of 104 children aged 6 months to 16 years with acute gastroenteritis, a single oral dose of ondansetron significantly reduced the duration of symptoms caused by rotavirus, with a median reduction of two days.

Ondansetron also decreased the number of diarrhea episodes, especially in children who had been ill for more than three days, suggesting it may help improve recovery and reduce the need for hospitalization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ondansetron treatment reduces rotavirus symptoms-A randomized double-blinded placebo-controlled trial. Hagbom, M., Novak, D., Ekström, M., et al.[2018]

References

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

Successful treatment of idiopathic secretory diarrhea of infancy with the somatostatin analogue SMS 201-995. [2019]

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

Severe posthemicolectomy diarrhea: evaluation and treatment with SMS 201-995. [2019]

3. Italy pubmed.ncbi.nlm.nih.gov

Long-acting octreotide as secondary prevention of chemotherapy-induced diarrhea: proof of concept. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Alternatives to Sulfasalazine: A Meta-analysis of 5-ASA in the Treatment of Ulcerative Colitis. [2018]

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

5-Aminosalicylic acid suppositories in the maintenance of remission in idiopathic proctitis or proctosigmoiditis: a double-blind placebo-controlled clinical trial. [2013]

6. Japan pubmed.ncbi.nlm.nih.gov

Effect of the 5-hydroxytryptamine3 (5-HT3)-receptor antagonist KB-R6933 on experimental diarrhea models. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Optimal dose of ramosetron in female patients with irritable bowel syndrome with diarrhea: A randomized, placebo-controlled phase II study. [2018]

8. Spain pubmed.ncbi.nlm.nih.gov

Cilansetron. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Cilansetron: a new serotonergic agent for the irritable bowel syndrome with diarrhoea. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Cilansetron in the treatment of diarrhea-predominant irritable bowel syndrome? [2012]

11. England pubmed.ncbi.nlm.nih.gov

5-HTP induced diarrhea as a carcinoid syndrome model in mice? [2019]

12. France pubmed.ncbi.nlm.nih.gov

[Treatment of acute chemically induced diarrhea by inhibition of enkephalinase. Results of a pilot study]. [2013]

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

Ondansetron treatment reduces rotavirus symptoms-A randomized double-blinded placebo-controlled trial. [2018]