Clinical trial NCT06153420: Study of the Research Medicine CIN-103 in Adults with Irritable Bowel Syndrome with Predominant Diarrhea (IBS-D).
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of CIN-103 in Adults with Irritable Bowel Syndrome with Predominant Diarrhea (IBS-D)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Irritable Bowel Syndrome with Diarrhea
Keywords: Irritable Bowel Syndrome
IBS-D
IBS
IBS with diarrhea
Abdominal pain with diarrhea
IBS with loose stool
Lead sponsor: CinPhloro Pharma, LLC
Sponsor class: INDUSTRY
First posted: 2023-12-01
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to evaluate if the study drug, CIN-103, can help reduce the symptoms associated with irritable bowel syndrome with predominant diarrhea (IBS-D) in adult patients. The main questions it aims to answer are:

* To evaluate the efficacy of CIN-103 on symptoms of IBS-D when given to patients with IBS-D compared to a placebo.
* To evaluate the safety and tolerability of CIN-103 when given to patients with IBS-D compared to a placebo

Participants will attend the following visits:

* Screening Period (1 Visit)
* Baseline Period (1 Visit)

  * Will complete daily diary and other Patient Reported Outcomes (PROs) as described in the protocol to assess eligibility for continued participation.
* 12-Week Treatment Period (5 Visits)

  * Study drug taken twice daily by mouth.
  * Will complete daily diaries and other PROs as described in the protocol.
* Follow- Up Period (1 Visit)

Researchers will compare CIN-103 Dose 1, CIN-103 Dose 2, and placebo, to evaluate the clinical response to multiple dose strengths of CIN-103 relative to placebo on abdominal pain and stool consistency along with safety and tolerability.


Eligibility criteria: * Inclusion Criteria:

  1. Are adult male and female subjects ≥ 18 years of age;
  2. Have a body mass index between 18 and 45 kg/m2, inclusive at Screening;
  3. Meet Rome IV Criteria for IBS-D by subject self-report of recurrent abdominal pain that is associated with ≥ 2 of the following over the last ≥ 6 months, with frequency of at least 1 day per week over the last 3 months (on average) before enrollment:

     1. Related to defecation;
     2. Associated with a change in frequency of stool; and/or
     3. Associated with a change in form (appearance of stool).
  4. Based on Investigator interview of subject's symptoms over the last 3 months, have ≥ 25% of bowel movements (BMs) with Bristol Stool Scale (BSS) Type 6 or 7 (loose or watery stools) and \< 25% of BMs with BSS Type 1 or 2 (lumpy or hard stools) per the Rome IV Criteria for IBS-D;
  5. In the opinion of the Investigator, are on a stable diet for ≥ 4 weeks prior to Screening and are not planning to change lifestyle, exercise, and/or diet that may impact symptoms of IBS-D during study participation;
  6. Have a fecal calprotectin ≤ 100 mcg/g at the Screening Visit or Visit 2; Note: A single normal test result is adequate for study eligibility. If subjects are rescreened within 12 months, there is no need for repeat fecal calprotectin sample collection and testing. However, subjects who fail screening due to a fecal calprotectin level \> 100 mcg/g are not eligible for re-screening. Note: Repeat Fecal calprotectin may be considered with prior Sponsor approval.
  7. Have a serum tTG-IgA (tissue transglutaminase immunoglobulin A) ≤ 4.99 FLU (fluorescent light units) at the Screening Visit;
  8. Have undergone a colonoscopy examination within the designated time interval prior to randomization, if they meet any of the following criteria. Note: A negative Cologuard® test result is an acceptable alternative to colonoscopy for subjects ≥ 45 years and at average risk for colon cancer.

     1. Average risk, based on US Preventive Services Task Force Recommendation Statement for screening of colorectal cancer, with age ≥ 45 years (colonoscopy within 10 years or negative test results on Cologuard within 3 years);
     2. Personal history of completely removed adenomatous colorectal polyps (colonoscopy within 5 years for polyps \> 1 cm, within 10 years for polyps \< 1 cm);
     3. History of colorectal cancer or adenomatous polyps in a first-degree relative before age 60 (colonoscopy within 5 years); or
     4. History of colorectal cancer or adenomatous polyps in ≥ 2 first-degree relatives at any age, or family history of hereditary colorectal cancer or polyposis (colonoscopy within 5 years).
* Exclusion Criteria:

  1. Have a diagnosis or suspected diagnosis of non-diarrhea predominant IBS (eg, IBS with a subtype of constipation, IBS with mixed or alternating bowel habits, un-subtyped IBS) or functional constipation by the Rome IV Criteria;
  2. Non-infectious chronic lower gastrointestinal conditions including a history of or current inflammatory bowel disease (ie, Crohn's disease, ulcerative colitis, indeterminate colitis), recurrent diverticulitis, microscopic colitis, lymphocytic colitis, celiac disease, non-celiac gluten sensitivity and non-compliant on a gluten-free diet, untreated lactose intolerance, carcinoid syndrome, Lynch syndrome, or familial polyposis, intestinal obstruction, stricture, toxic megacolon, solitary rectal ulcer syndrome, GI perforation, intra-abdominal or pelvic adhesions, ischemic colitis, radiation proctitis, chronic enteritis, non-infectious colitis, or impaired intestinal circulation (eg, aortoiliac disease);

     Note: Lactose intolerance and non-celiac gluten sensitivity will not exclude a subject from participation if the Investigator documents that the subject is compliant on a special diet (lactose-free diet or gluten-free diet, respectively) and/or for lactose intolerance is successfully treated with commercial lactase supplement(s).
  3. Infectious lower gastrointestinal conditions requiring antibiotics or microbiome therapy; any microbiologically documented acute lower gastrointestinal colitis or enteritis requiring antibiotic treatment including successfully treated Clostridioides difficile colitis within 3 months prior to Screening, or a history of recurrent C. difficile colitis at any time in the past;
  4. Have a known family history of inflammatory bowel disease in at least 1 first-degree relative;
  5. Have a known history of a pelvic floor disorder associated with constipation (unless successful treatment has been documented by a normal balloon expulsion test or anorectal manometry), refractory constipation not responsive to standard medical therapy, fecal impaction that required hospitalization, cathartic colon, and/or active proctological condition;
  6. Have a history of or current non-IBS chronic condition(s) with ongoing symptoms associated with abdominal pain or GI discomfort (eg, gastroparesis, functional dyspepsia, uncontrolled gastroesophageal reflux disease, polycystic kidney disease, ovarian cysts, urological pain, or endometriosis);
  7. Have a history of or current clinically significant arrhythmias as judged by the Investigator, including ventricular tachycardia, ventricular fibrillation, and Torsades de pointes. Subjects with any abnormal electrocardiogram (ECG) not considered clinically significant by the Investigator are not excluded;
  8. Have current or a history of diverticulitis, heme positive stool, or unexplained GI bleeding within 3 months prior to Screening.

     Note: Surgically repaired diverticulitis \> 3 months prior to Screening is permitted.
  9. Have a history of surgical resection of the stomach, small, or large intestine;
  10. Have had any major abdominal surgery within the 3 months prior to Screening;

      Note: Permitted procedures are uncomplicated appendectomy, cholecystectomy, and resection of benign polyps within the 3 months prior to Screening. Subjects who had an appendectomy that was associated with any related complications or sequelae are eligible if the procedure was performed at least 6 months prior to Screening.
  11. Are currently undergoing or planning to initiate treatment with weight loss medication during study participation or prior weight loss surgery (eg, gastric bypass surgery, gastric banding);
  12. Have a planned invasive elective surgery during the period of anticipated study participation from the time of informed consent through the last study visit;

Primary outcomes:
measure: Occurrence of meeting Study Composite Responder status for an adult subject with IBS-D.
timeFrame: 12 weeks of Double Blind Treatment Period
Secondary outcomes:
measure: The occurrence of meeting Weekly Composite Responder status
timeFrame: 12-week of Double-Blind Treatment Period
measure: The occurrence of meeting Weekly Composite Responder status over 4-weekly intervals (1 to 4, 5 to 8, and 9 to 12 weeks).
timeFrame: 12 weeks of Double Blind Treatment Period
measure: The change in a composite of the daily mean and weekly mean of daily WAP score and stool consistency score as compared to Baseline
timeFrame: 12-week of Double-Blind Treatment Period
measure: The change in daily mean and weekly mean number of BMs per day compared to Baseline
timeFrame: 12-week of Double-Blind Treatment Period
measure: The occurrence of meeting Stool Consistency Responder status
timeFrame: 12-week of Double-Blind Treatment Period
measure: The change in the daily mean and weekly mean of stool consistency measured with the Bristol Stool Scale (BSS) as compared to Baseline
timeFrame: 12-week of Double-Blind Treatment Period
measure: The occurrence of meeting Pain Responder status
timeFrame: 12-week of Double-Blind Treatment Period
measure: The change in the daily mean and weekly mean of daily WAP as compared to Baseline
timeFrame: 12-week of Double-Blind Treatment Period
measure: The change in the daily mean and weekly mean of daily abdominal bloating score as compared to Baseline.
timeFrame: 12-week of Double-Blind Treatment Period
measure: The change in the daily mean and weekly mean of daily urgency score compared to Baseline.
timeFrame: 12-week of Double-Blind Treatment Period
measure: The change in daily mean and weekly mean number of fecal incontinence episodes compared to Baseline
timeFrame: 12-week of Double-Blind Treatment Period
measure: Incidence of clinically significant changes, in the Investigator's opinion, in vital signs, physical examinations, ECGs, and clinical laboratory evaluations.
timeFrame: Through study completion, up to 19 weeks.
measure: Occurrence of Treatment-Emergent Adverse Events (TEAEs).
timeFrame: Through study completion, up to 19 weeks.
measure: Occurrence of treatment-emergent serious adverse events.
timeFrame: Through study completion, up to 19 weeks.
measure: Occurrence of TEAEs leading to premature discontinuation of the study drug.
timeFrame: Through study completion, up to 19 weeks.
measure: Occurrence of treatment-emergent clinically significant laboratory abnormalities.
timeFrame: Through study completion, up to 19 weeks.
measure: Percentage of post-randomization days with symptom of urgency present ("Yes")
timeFrame: 12-week of Double-Blind Treatment Period
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Digestive Health Specialists - Dothan
state: Alabama
city: Huntsville
country: United States
facility: Clinical Research Associates, LLC
state: Alabama
city: Phoenix
country: United States
facility: Elite Clinical Studies LLC
state: Arizona
city: Sun City
country: United States
facility: GI Alliance - Sun City
state: Arizona
city: Little Rock
country: United States
facility: Applied Research Center of Arkansas
state: Arkansas
city: Garden Grove
country: United States
facility: Paragon Rx Clinical, Inc. - Garden Grove
state: California
city: Lancaster
country: United States
facility: Gastro Care Institute- lancaster
state: California
city: San Diego
country: United States
facility: Medical Associates Research Group
state: California
city: Cape Coral
country: United States
facility: American Family Research Group
state: Florida
city: Doral
country: United States
facility: USA and International Research Inc.
state: Florida
city: Miami
country: United States
facility: International Research Associates LLC
state: Florida
city: Palmetto Bay
country: United States
facility: Innovation Medical Research Center
state: Florida
city: Savannah
country: United States
facility: Velocity Clinical Research,, Savannah
state: Georgia
city: Oak Lawn
country: United States
facility: Southwest Gastroenterology
state: Illinois
city: Mandeville
country: United States
facility: DelRicht Research
state: Louisiana
city: Marrero
country: United States
facility: Tandem Clinical Research GI LLC
state: Louisiana
city: Metairie
country: United States
facility: Tandem Clinical Research GI LLC
state: Louisiana
city: New Orleans
country: United States
facility: DelRicht Research
state: Louisiana
city: West Monroe
country: United States
facility: Delta Research Partners, LLC
state: Louisiana
city: Rockville
country: United States
facility: DelRicht Research of Bethesda Clinical Trials
state: Maryland
city: Weldon Spring
country: United States
facility: St. Charles Clinical Research
state: Missouri
city: Omaha
country: United States
facility: Quality Clinical Research, Inc
state: Nebraska
city: Las Vegas
country: United States
facility: Las Vegas Medical Research
state: Nevada
city: Las Vegas
country: United States
facility: Digestive Disease Specialists
state: Nevada
city: Reno
country: United States
facility: Advanced Research Institute - Reno
state: Nevada
city: Somers Point
country: United States
facility: Allied Digestive Health Clinical Research Organization
state: New Jersey
city: Somers Point
country: United States
facility: Allied Digestive Health-Jersey Shore Gastroenterology - Point Commons
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials, Inc
state: New Mexico
city: Carmel hamlet
country: United States
facility: Westchester Putnam Gastro
state: New York
city: New York
country: United States
facility: IMA Clinical Research PC and Affiliates- New York, NY
state: New York
city: New York
country: United States
facility: NY Scientific
state: New York
city: Charlotte
country: United States
facility: Atrium Health - Center for Gastroenterology and Hepatology MMP
state: North Carolina
city: High Point
country: United States
facility: Peters Medical Research
state: North Carolina
city: Mount Airy
country: United States
facility: IMA Clinical Research
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Remington Davis, Inc.
state: Ohio
city: Mentor
country: United States
facility: Great Lakes Gastroenterology Research LLC
state: Ohio
city: Westlake
country: United States
facility: Northshore Gastroenterology Research, LLC
state: Ohio
city: Tulsa
country: United States
facility: Options Health Research LLC
state: Oklahoma
city: Harrisburg
country: United States
facility: Susquehanna Research Group, LLC
state: Pennsylvania
city: Charleston
country: United States
facility: DelRicht Research of Charleston Clinical Trials
state: South Carolina
city: Summerville
country: United States
facility: Palmetto Clinical Research
state: South Carolina
city: Chattanooga
country: United States
facility: Galen Medical Group - Downtown Gastroenterology Location
state: Tennessee
city: Kingsport
country: United States
facility: Tri-Cities Gastroenterology
state: Tennessee
city: Union City
country: United States
facility: Advanced Gastroenterology
state: Tennessee
city: Bellaire
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Houston
country: United States
facility: The Clinical Trials Network LLC
state: Texas
city: Houston
country: United States
facility: Care and Cure Clinic
state: Texas
city: Pharr
country: United States
facility: GLRI - McAllen Research
state: Texas
city: San Antonio
country: United States
facility: Quality Research Inc
state: Texas
city: San Antonio
country: United States
facility: Gastroenterology Research of San Antonio
state: Texas
city: Ogden
country: United States
facility: Advanced Research Institute
state: Utah
city: Tacoma
country: United States
facility: GI Alliance - Washington Gastroenterology
state: Washington
Study officials:
References: