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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03595553




Registration number
NCT03595553
Ethics application status
Date submitted
11/06/2018
Date registered
23/07/2018
Date last updated
3/03/2023

Titles & IDs
Public title
Comparison of Ridinilazole Versus Vancomycin Treatment for Clostridium Difficile Infection
Scientific title
A Phase 3, Randomized, Double-blind, Active Controlled Study to Compare the Efficacy and Safety of Ridinilazole (200 mg, Bid) for 10 Days With Vancomycin (125 mg, Qid) for 10 Days in the Treatment of Clostridium Difficile Infection (CDI)
Secondary ID [1] 0 0
SMT19969/C004
Universal Trial Number (UTN)
Trial acronym
Ri-CoDIFy 1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Clostridioides Difficile Infection 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ridinilazole
Treatment: Drugs - Vancomycin

Experimental: ridinilazole - ridinilazole 200mg bid

Active comparator: vancomycin - vancomycin 125 mg qid


Treatment: Drugs: Ridinilazole
ridinilazole (200 mg bid)

Treatment: Drugs: Vancomycin
vancomycin (125 mg qid)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Sustained Clinical Response (SCR) Defined as Clinical Response and no Recurrence of CDI Through 30 Days Post End of Treatment (EOT).
Timepoint [1] 0 0
Day 40
Secondary outcome [1] 0 0
Clinical Response
Timepoint [1] 0 0
Day 12
Secondary outcome [2] 0 0
Clinical Cure
Timepoint [2] 0 0
Day 12
Secondary outcome [3] 0 0
Sustained Clinical Response Over 60 Days
Timepoint [3] 0 0
Day 70
Secondary outcome [4] 0 0
Sustained Clinical Response Over 90 Days
Timepoint [4] 0 0
Day 100
Secondary outcome [5] 0 0
Relative Abundance of the 3 Main Bile Acid Groups (Conjugated Primary, Primary and Secondary Bile Acids) From Baseline to EOT.
Timepoint [5] 0 0
Day 10
Secondary outcome [6] 0 0
Percentage of Change of a-diversity (Shannon Index) of the Microbiota in Stool Samples From Baseline to EOT.
Timepoint [6] 0 0
Day 10
Secondary outcome [7] 0 0
Measure of ß-diversity of the Gut Microbiota Between Baseline and EOT Stool Samples (Bray-Curtis Index/Dissimilarity).
Timepoint [7] 0 0
Day 10

Eligibility
Key inclusion criteria
Inclusion Criteria

Patients are eligible to be included in the study only if all the following criteria apply:

1. Patient must be at least 18 years of age, at the time of signing the informed consent.
2. Have signs and symptoms of CDI including diarrhea such that in the Investigator's opinion, CDI antimicrobial therapy is required. Diarrhea is defined as a change in bowel habits, with =3 unformed bowel movements (UBMs) (5, 6 or 7 on the Bristol Stool Chart) in the 24 h prior to randomization.
3. Have the presence of either toxin A and/or B of C. difficile in the stool determined by a positive free toxin test (using a Sponsor agreed test). The stool sample must be current (produced within 72 hours prior to randomization).
4. Male or Female

Male patients:

• A male patient must agree to use contraception as detailed in Section 10.4 of this protocol during the treatment period and for at least 30 days after the last dose of study treatment and refrain from donating sperm during this period.

Female patients:

• A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: i. Not a woman of childbearing potential (WOCBP) OR ii. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days after the last dose of study treatment.
5. Has provided documented signed informed consent and any authorizations required by local law (e.g. Protected Health Information [PHI]). If unable to read, understand and sign the informed consent form a legally authorized representative (LAR) may provide consent on the patient's behalf if permitted by the Institutional Review Board (IRB)/Ethics Committee (EC).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

Patients are excluded from the study if any of the following criteria apply:

1. Have had more than one prior episode of CDI in the previous 3 months or more than 3 episodes in the past 12 months prior to randomization.
2. Have a history of chronic diarrheal disease including inflammatory bowel disease (Crohn's disease or ulcerative colitis).
3. Have had a positive diagnostic test for other GI pathogens, considered to be clinically relevant, within 2 weeks of randomization.
4. Have had major gastrointestinal (GI) surgery (e.g. significant bowel resection) within 3 months of randomization (this does not include appendectomy). The presence of a colostomy or ileostomy or likely requirement of an ostomy during the study.
5. Have life threatening or fulminant CDI with evidence of hypotension, septic shock, peritoneal signs or absence of bowel sounds, or toxic megacolon.
6. History of bone marrow or hematopoietic stem cell transplant at any time or a known current history of a severely compromised/suppressed immune system that, in the opinion of the Investigator, would make the patient unsuitable for the study.
7. Have had more than the equivalent of 24 hours of dosing of antimicrobial treatment active against the current episode of CDI prior to randomization. (i.e. more than four doses of oral vancomycin, two doses of fidaxomicin or three doses of metronidazole).
8. Prior or current use of anti-toxin antibodies including bezlotoxumab within the past 6 months prior to randomization.
9. Are unable to discontinue products used affecting disease progression at randomization.
10. Has been involved in a clinical trial and received an investigational medicinal product for indications other than CDI within 1 month or five half-lives (whichever is longer) or within 3 months if the investigational medical product was for CDI.
11. Have received an investigational vaccine against C. difficile.
12. Patients that the Investigator feels are inappropriate for the study this would include those;

1. with any other condition that, in the Investigator's judgment, would make the patient unsuitable for inclusion in the study.
2. who, in the opinion of the Investigator, are not likely to complete the study for whatever reason, e.g. short life expectancy.
3. with known hypersensitivity or intolerance to ridinilazole, vancomycin, and/or their excipients
4. who are unwilling or unable to comply with protocol requirements, e.g. complete the full course of study treatment per schedule, attend study visits, report diarrhea/suspected recurrence, provide stool samples, ingest capsules/tablets or blood draws.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/01/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/11/2021
Sample size
Target
Accrual to date
Final
759
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Westmead Hospital - Westmead
Recruitment hospital [2] 0 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [3] 0 0
Mater Misericordiae - South Brisbane
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [5] 0 0
Monash Medical Center - Clayton
Recruitment hospital [6] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4575 - Birtinya
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Idaho
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Montana
Country [14] 0 0
United States of America
State/province [14] 0 0
Nevada
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
South Dakota
Country [20] 0 0
United States of America
State/province [20] 0 0
Tennessee
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Virginia
Country [23] 0 0
Argentina
State/province [23] 0 0
Buenos Aires
Country [24] 0 0
Argentina
State/province [24] 0 0
Cordoba
Country [25] 0 0
Argentina
State/province [25] 0 0
Salta
Country [26] 0 0
Brazil
State/province [26] 0 0
Minas Gerais
Country [27] 0 0
Brazil
State/province [27] 0 0
Rio Grande Do Sul
Country [28] 0 0
Brazil
State/province [28] 0 0
Sao Paulo
Country [29] 0 0
Bulgaria
State/province [29] 0 0
Kyustendil
Country [30] 0 0
Bulgaria
State/province [30] 0 0
Blagoevgrad
Country [31] 0 0
Bulgaria
State/province [31] 0 0
Sliven
Country [32] 0 0
Bulgaria
State/province [32] 0 0
Sofia
Country [33] 0 0
Canada
State/province [33] 0 0
Alberta
Country [34] 0 0
Canada
State/province [34] 0 0
New Brunswick
Country [35] 0 0
Canada
State/province [35] 0 0
Ontario
Country [36] 0 0
Canada
State/province [36] 0 0
Quebec
Country [37] 0 0
Greece
State/province [37] 0 0
Athens
Country [38] 0 0
Greece
State/province [38] 0 0
Heraklion
Country [39] 0 0
Greece
State/province [39] 0 0
Patras
Country [40] 0 0
Greece
State/province [40] 0 0
Piraeus
Country [41] 0 0
Hungary
State/province [41] 0 0
Békés
Country [42] 0 0
Hungary
State/province [42] 0 0
Pest Megye
Country [43] 0 0
Hungary
State/province [43] 0 0
Balassagyarmat
Country [44] 0 0
Hungary
State/province [44] 0 0
Budapest
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Hungary
State/province [45] 0 0
Békéscsaba
Country [46] 0 0
Hungary
State/province [46] 0 0
Miskolc
Country [47] 0 0
Hungary
State/province [47] 0 0
Pécs
Country [48] 0 0
Hungary
State/province [48] 0 0
Szentes
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Hungary
State/province [49] 0 0
Vác
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Korea, Republic of
State/province [50] 0 0
Gangwon-do
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Korea, Republic of
State/province [51] 0 0
Gangwondo
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Korea, Republic of
State/province [52] 0 0
Gyeonggi-do
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Korea, Republic of
State/province [53] 0 0
Seoul
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Korea, Republic of
State/province [54] 0 0
Yeongnam
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Korea, Republic of
State/province [55] 0 0
Junggu
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Korea, Republic of
State/province [56] 0 0
Soeul
Country [57] 0 0
New Zealand
State/province [57] 0 0
Auckland
Country [58] 0 0
New Zealand
State/province [58] 0 0
Taranki
Country [59] 0 0
New Zealand
State/province [59] 0 0
Waikato
Country [60] 0 0
Poland
State/province [60] 0 0
Podkarpackie
Country [61] 0 0
Poland
State/province [61] 0 0
Bochnia
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Poland
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Bydgoszcz
Country [63] 0 0
Poland
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Chorzów
Country [64] 0 0
Poland
State/province [64] 0 0
Katowice
Country [65] 0 0
Poland
State/province [65] 0 0
Krakow
Country [66] 0 0
Poland
State/province [66] 0 0
Rzeszow
Country [67] 0 0
Poland
State/province [67] 0 0
Sopot
Country [68] 0 0
Poland
State/province [68] 0 0
Warszawa
Country [69] 0 0
Poland
State/province [69] 0 0
Wroclaw
Country [70] 0 0
Romania
State/province [70] 0 0
Bucuresti
Country [71] 0 0
Romania
State/province [71] 0 0
Caracal
Country [72] 0 0
Romania
State/province [72] 0 0
Constanta
Country [73] 0 0
Romania
State/province [73] 0 0
Iasi
Country [74] 0 0
Romania
State/province [74] 0 0
Timi?oara
Country [75] 0 0
Russian Federation
State/province [75] 0 0
Moscow
Country [76] 0 0
Russian Federation
State/province [76] 0 0
Novosibirsk
Country [77] 0 0
Spain
State/province [77] 0 0
Barakaldo
Country [78] 0 0
Spain
State/province [78] 0 0
Barcelona
Country [79] 0 0
Spain
State/province [79] 0 0
Córdoba
Country [80] 0 0
Spain
State/province [80] 0 0
Donostia
Country [81] 0 0
Spain
State/province [81] 0 0
Madrid
Country [82] 0 0
Spain
State/province [82] 0 0
Santander
Country [83] 0 0
Spain
State/province [83] 0 0
Sevilla
Country [84] 0 0
Spain
State/province [84] 0 0
Tarragona

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Summit Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Summit is developing ridinilazole as a novel antimicrobial for Clostridioides difficile Infection (CDI), formerly known as Clostridium difficile Infection, with the goal of demonstrating an improved Sustained Clinical Response rate in subjects treated with ridinilazole as compared to subjects treated with vancomycin.

A phase 2 proof of concept study, with vancomycin as comparator, demonstrated these attributes with a comparable safety profile. A high fecal concentration of ridinilazole and little systemic exposure were noted.

The rationale for this phase 3 study is to confirm the improvement in sustained clinical response of CDI over vancomycin and to compare the safety and tolerability of ridinilazole to that of vancomycin.

Ridinilazole plasma concentration will be assessed in a subset of patients.
Trial website
https://clinicaltrials.gov/study/NCT03595553
Trial related presentations / publications
Carlson TJ, Endres BT, Basseres E, Gonzales-Luna AJ, Garey KW. Ridinilazole for the treatment of Clostridioides difficile infection. Expert Opin Investig Drugs. 2019 Apr;28(4):303-310. doi: 10.1080/13543784.2019.1582640. Epub 2019 Feb 26.
Public notes

Contacts
Principal investigator
Name 0 0
Lori Styles, MD
Address 0 0
Summit Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03595553