Safety, Tolerability and the Pharmacokinetics of Ridinilazole in Adolescent Subjects (Ri-CoDIFy 3)

A Randomized, Double Blind, Active Controlled Study to Evaluate the Safety and Tolerability of Ridinilazole Compared With Vancomycin and to Assess the Pharmacokinetics of Ridinilazole in Adolescent Subjects (Aged 12 to <18 Years) With Clostridioides Difficile Infection

Study to evaluate the safety of ridinilazole in adolescent subjects and how ridinilazole is metabolized.

Study Overview

• Status: Terminated
• Conditions: Clostridioides Difficile Infection
• Intervention / Treatment: Drug: Ridinilazole; Drug: Vancomycin

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles (UCLA) David Geffen School of Medicine
    • Orange, California, United States, 92868
      • Children's Hospital Orange County
  • Florida
    • Miami, Florida, United States, 33144
      • Continental Clinical Research
    • Miami, Florida, United States, 33144
      • Dynamic Medical Research LLC
    • Miami, Florida, United States, 33155
      • D&H National Research Centers
    • Orlando, Florida, United States, 32819
      • HMD Research
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Children's Center For Digestive Health
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Snake River Research
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann and Robert H Lurie Children's Hospital of Chicago
    • Chicago, Illinois, United States, 60637
      • University of Chicago - Comer Children's Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health - Riley Hospital for Children
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 11758
      • DiGiovanna Institute for Medical Education And Research
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center - Rainbow Babies and Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 15 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Is aged 12 to <18 years.
• Has signs and symptoms of CDI including diarrhea such that in the Investigator's opinion CDI antimicrobial therapy is required, and the subject has tested positive for toxin A and/or B of C. difficile in the stool. Diarrhea is defined as ≥ 3 unformed bowel movements (UBMs) based on types 5, 6, 7 on the Bristol Stool Chart and diarrhea information is within 24 hours prior to randomization.

Exclusion Criteria:

• Has had more than the equivalent of 48 hours of dosing of antimicrobial treatment active against the current episode of CDI prior to randomization.
• Has received ridinilazole or an investigational vaccine against C. difficile any time in the past, anti-toxic antibodies including bezlotoxumab within the past 6 months, or any other investigational medicinal product for treatment of CDI or fecal microbiota replacement therapy within the past 3 months.
• Has a clinically relevant positive stool test for pathogens other than C. difficile, within 48 hours of randomization.
• Has life-threatening or fulminant CDI with evidence of hypotension, septic shock, peritoneal signs or absence of bowel sounds, toxic megacolon, or ileus.
• Has had major GI surgery (e.g. significant bowel resection or pancreatectomy but not including appendectomy or cholecystectomy) within past 3 months or has the presence of a colostomy or ileostomy or has the likely requirement of an ostomy during the study.
• Is receiving treatment that generally is associated with severe diarrhea, intractable vomiting, severe nausea, or inability to swallow that cannot be managed with antiemetics or antidiarrheals and that limits the ability to take oral medications. Cancer treatment that does not comprise ability to take study medication or cause severe diarrhea is allowed.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ridinilazole; Ridinilazole dosed BID and a comparator placebo dosed QID, to maintain blind, for 40 doses over 10 days.	Drug: Ridinilazole; Ridinilazole 200mg dosed BID for 10 days.
Active Comparator: Vancomycin; Vancomycin dosed QID and a Ridinilazole placebo dosed BID, to maintain blind, for 40 doses over 10 days.	Drug: Vancomycin; Vancomycin 125mg dosed QID for 10 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Treatment-emergant Adverse Events	Safety was assessed using CTCAE v4.	Until study completion (Day 100)

Secondary Outcome Measures

Outcome Measure	Time Frame
Sustained clinical response (SCR) over 30 days post end of treatment (EOT) - defined as clinical cure at the assessment of cure (AOC) visit and no recurrence of CDI within 30 days post EOT	30 days post EOT
Clinical cure at the assessment of cure (AOC) visit	Day 12
Sustained clinical response over 60 days post EOT	60 days post EOT
Sustained clinical response over 90 days post EOT	90 days post EOT
SCR based on clinical response - defined as clinical response with no recurrence assessed through 30 days post-EOT	30 days post EOT
Clinical response at the AOC visit	Day 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medical resource utilization and health economics endpoints	Data will include length of hospital stay, hospital admission and readmission rates and reasons for admission, subject location at admission and subject's discharge location, other location of healthcare access that didn't result in hospitalization i.e. urgent care facility, doctor visit, telemedicine.	Day 1 through Study Completion, an average of 100 days

Collaborators and Investigators

• Sponsor: Summit Therapeutics
• Collaborators: Department of Health and Human Services
• Investigators: Study Director: Lori Styles, MD, Summit Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2021
• Primary Completion (Actual): September 17, 2021
• Study Completion (Actual): September 28, 2022

Study Registration Dates

• First Submitted: March 9, 2021
• First Submitted That Met QC Criteria: March 15, 2021
• First Posted (Actual): March 17, 2021

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Adolescents; Diarrhea; Infection; Pediatric; Clostridium difficile; vancomycin; C. Diff; Clostridioides difficile infection (CDI); ridinilazole
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Clostridium Infections; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Ridinilazole
• Other Study ID Numbers: SMT19969/C006; HHSO100201700014C (Other Identifier: Department of Health and Human Services)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No