Clinical Trials List
Protocol NumberVE303-003
NCT Number(ClinicalTrials.gov Identfier)NCT06237452
Not yet recruiting
2025-04-01 - 2027-11-30
Phase III
Recruiting3
A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of VE303 for Prevention of Recurrent Clostridioides Difficile Infection
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Trial Applicant
PAREXEL INTERNATIONAL CO., LTD.
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Sponsor
Parexel International
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Po-Yan Huang Division of Infectious Disease
- Chia-Jung Kuo Division of Infectious Disease
- 鄭鈞文 Division of Infectious Disease
- Ting-Shu Wu Division of Infectious Disease
- Nan-Yu Chen Division of Infectious Disease
- 謝顯森 Division of Infectious Disease
- Puo-Hsien Le Division of Infectious Disease
- 陳建彰 Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 蘇浤傑 Division of Infectious Disease
- Ho Mao-Wang Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Po-Liang Lu
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Prevention of recurrent Clostridioides difficile infection (CDI)
Objectives
The overall objective of the RESTORATiVE303 study is to evaluate the safety and recurrence rate of Clostridioides difficile infection (CDI) at Week 8 in participants receiving a 14-day course of VE303 or a matching placebo.
The objectives and endpoints are the same for Stage 1 (recurrent CDI) and Stage 2 (high-risk primary CDI); however, the analyses and evaluations of endpoints for Stage 1 and Stage 2 will be conducted separately.
Test Drug
VE303
Active Ingredient
VE303
Dosage Form
N/A
Dosage
-
Endpoints
Double-blind, placebo-controlled trial:
Proportion of participants with laboratory-confirmed recurrence of Clostridioides difficile infection (CDI) through Week 8.
Proportion of participants with laboratory-confirmed recurrence of Clostridioides difficile infection (CDI) through Week 8.
Inclution Criteria
Stage 1 Enrollment (Recurrent Clostridioides difficile Infection, rCDI Cohort):
Participants aged ≥12 years (in countries allowing adolescent inclusion) and ≥18 years (in other countries) with a laboratory-confirmed qualifying episode of Clostridioides difficile infection (CDI) and at least one prior CDI episode within the past 6 months.
Stage 2 Enrollment (High-Risk Primary Clostridioides difficile Infection, pCDI-hr Cohort):
2. Participants aged ≥75 years with a laboratory-confirmed qualifying CDI episode, or
3. Participants aged 12–74 years (in countries allowing adolescent inclusion) or 18–74 years (in other countries) with a laboratory-confirmed qualifying CDI episode and at least two of the following risk factors:
– Age ≥65 years
– Renal impairment, defined as an estimated creatinine clearance <60 mL/min/1.73m² at the time of qualifying CDI
– Chronic use of proton pump inhibitors (PPIs) within the past 2 months, with anticipated continuation during the study
– History of CDI occurring within 6–12 months prior to enrollment
– Immunosuppression due to underlying disease or its treatment
– History of solid organ or hematopoietic stem cell transplantation
For both Stage 1 and Stage 2 enrollment:
4. The qualifying CDI episode must meet all of the following criteria:
a. ≥3 new unformed stools within 24 hours (Bristol Stool Scale types 5–7) for at least 2 consecutive days.
b. Onset of CDI symptoms within 4 weeks prior to initiation of standard-of-care (SoC) antibiotic therapy for CDI.
c. Positive stool test for C. difficile toxin A/B (by EIA) and GDH prior to or within 72 hours after starting SoC antibiotics. If GDH/toxin results are discordant, a reflex PCR must confirm positivity, performed by a local or central laboratory.
d. Diarrhea is considered unlikely to be caused by an alternative etiology.
Before receiving study drug, participants must:
a. Have completed 10–28 days of SoC antibiotic therapy for CDI (selected at the investigator’s discretion; tapering regimens are not permitted).
b. Meet criteria for clinical cure, defined as resolution of CDI symptoms (fewer than 3 unformed stools per 24 hours for at least 2 consecutive days).
Participants of childbearing potential must have a negative pregnancy test and agree to use a highly effective form of contraception during the study and for up to 3 months after the last study drug dose.
Acceptable methods (failure rate <1% per year with consistent use) include:
– Hormonal contraception that suppresses ovulation (implant, injection, combined oral contraceptive, hormonal IUD)
– Non-hormonal intrauterine device (IUD, copper)
– Complete abstinence (as a consistent lifestyle choice)
– Sexual activity only with a vasectomized partner with confirmed azoospermia
Periodic abstinence, withdrawal, spermicide-only methods, and lactational amenorrhea are not acceptable.
Able to receive the first dose of study drug either on the final scheduled day of SoC antibiotic therapy or within 2 days after completion of antibiotic treatment.
Clinically recovered and stable from any complications of severe or fulminant CDI at the time of randomization.
Able and willing to comply with study procedures (e.g., oral capsule ingestion, scheduled visits, sample collection for blood and stool, completion of questionnaires).
Able and willing to provide written informed consent/assent prior to any study-specific procedures or drug administration, understanding the potential risks and benefits of participation.
Where applicable, consent may be provided by a legally authorized representative (LAR). For participants below the legal age of consent (generally <18 years), consent must be signed by the parent/guardian (and co-signed by the participant, if appropriate) using a child-specific consent form, in accordance with local regulations and ethical practice.
Participants aged ≥12 years (in countries allowing adolescent inclusion) and ≥18 years (in other countries) with a laboratory-confirmed qualifying episode of Clostridioides difficile infection (CDI) and at least one prior CDI episode within the past 6 months.
Stage 2 Enrollment (High-Risk Primary Clostridioides difficile Infection, pCDI-hr Cohort):
2. Participants aged ≥75 years with a laboratory-confirmed qualifying CDI episode, or
3. Participants aged 12–74 years (in countries allowing adolescent inclusion) or 18–74 years (in other countries) with a laboratory-confirmed qualifying CDI episode and at least two of the following risk factors:
– Age ≥65 years
– Renal impairment, defined as an estimated creatinine clearance <60 mL/min/1.73m² at the time of qualifying CDI
– Chronic use of proton pump inhibitors (PPIs) within the past 2 months, with anticipated continuation during the study
– History of CDI occurring within 6–12 months prior to enrollment
– Immunosuppression due to underlying disease or its treatment
– History of solid organ or hematopoietic stem cell transplantation
For both Stage 1 and Stage 2 enrollment:
4. The qualifying CDI episode must meet all of the following criteria:
a. ≥3 new unformed stools within 24 hours (Bristol Stool Scale types 5–7) for at least 2 consecutive days.
b. Onset of CDI symptoms within 4 weeks prior to initiation of standard-of-care (SoC) antibiotic therapy for CDI.
c. Positive stool test for C. difficile toxin A/B (by EIA) and GDH prior to or within 72 hours after starting SoC antibiotics. If GDH/toxin results are discordant, a reflex PCR must confirm positivity, performed by a local or central laboratory.
d. Diarrhea is considered unlikely to be caused by an alternative etiology.
Before receiving study drug, participants must:
a. Have completed 10–28 days of SoC antibiotic therapy for CDI (selected at the investigator’s discretion; tapering regimens are not permitted).
b. Meet criteria for clinical cure, defined as resolution of CDI symptoms (fewer than 3 unformed stools per 24 hours for at least 2 consecutive days).
Participants of childbearing potential must have a negative pregnancy test and agree to use a highly effective form of contraception during the study and for up to 3 months after the last study drug dose.
Acceptable methods (failure rate <1% per year with consistent use) include:
– Hormonal contraception that suppresses ovulation (implant, injection, combined oral contraceptive, hormonal IUD)
– Non-hormonal intrauterine device (IUD, copper)
– Complete abstinence (as a consistent lifestyle choice)
– Sexual activity only with a vasectomized partner with confirmed azoospermia
Periodic abstinence, withdrawal, spermicide-only methods, and lactational amenorrhea are not acceptable.
Able to receive the first dose of study drug either on the final scheduled day of SoC antibiotic therapy or within 2 days after completion of antibiotic treatment.
Clinically recovered and stable from any complications of severe or fulminant CDI at the time of randomization.
Able and willing to comply with study procedures (e.g., oral capsule ingestion, scheduled visits, sample collection for blood and stool, completion of questionnaires).
Able and willing to provide written informed consent/assent prior to any study-specific procedures or drug administration, understanding the potential risks and benefits of participation.
Where applicable, consent may be provided by a legally authorized representative (LAR). For participants below the legal age of consent (generally <18 years), consent must be signed by the parent/guardian (and co-signed by the participant, if appropriate) using a child-specific consent form, in accordance with local regulations and ethical practice.
Exclusion Criteria
History of chronic diarrhea unrelated to Clostridioides difficile infection within 3 months prior to randomization (defined as ≥3 loose stools per day lasting for at least 4 weeks).
Confirmed infectious diarrhea other than CDI during the qualifying CDI episode (including bacterial, viral, or parasitic etiologies).
Known or suspected toxic megacolon or small bowel obstruction at the time of randomization.
Confirmed colonic disease, including inflammatory bowel disease, microscopic colitis, short bowel syndrome, gastrointestinal (GI) fistula, or a recent episode (within 6 months) of intestinal ischemia or ischemic colitis.
Contraindication to oral/enteral therapy at randomization (e.g., severe reflux, severe nausea/vomiting, or bowel obstruction).
White blood cell count >15.0 × 10⁹ cells/L within 7 days prior to randomization.
Absolute neutrophil count (ANC) <0.5 × 10⁹ cells/L on two consecutive occasions within 7 days prior to randomization, or persistent ANC <1.0 × 10⁹ cells/L.
Receipt of bezlotoxumab during the standard-of-care antibiotic treatment course for the qualifying CDI episode.
Use of antidiarrheal agents (e.g., loperamide, diphenoxylate) within 3 days prior to the first dose of study drug.
Expected need for oral or parenteral antibiotic therapy for non-CDI indications from randomization through Week 24 (end of study).
History of malignancy within 2 months prior to randomization, with receipt of chemotherapy or other treatments known to cause gastrointestinal adverse effects.
Receipt of any investigational drug or vaccine within 30 days prior to randomization.
Current or anticipated need for mechanical ventilation or vasopressor support for hemodynamic stabilization.
Life expectancy <3 months.
Major gastrointestinal surgery (e.g., large bowel resection or diversion procedure) within 3 months prior to randomization; current ileostomy; or prior total colectomy.
Participants with a history of appendectomy, cholecystectomy, or bariatric surgery (e.g., gastric banding) may be eligible upon discussion with the medical monitor, provided the procedure was completed at least 1 month before randomization and the participant has fully recovered.
Pregnant or breastfeeding.
Known hypersensitivity, allergy, or intolerance to any component of the VE303 formulation.
Any clinically significant or uncontrolled medical or surgical condition not specified above that, in the investigator’s opinion, could interfere with study drug administration, the interpretation of safety or efficacy results, or compromise participant safety or well-being.
Confirmed infectious diarrhea other than CDI during the qualifying CDI episode (including bacterial, viral, or parasitic etiologies).
Known or suspected toxic megacolon or small bowel obstruction at the time of randomization.
Confirmed colonic disease, including inflammatory bowel disease, microscopic colitis, short bowel syndrome, gastrointestinal (GI) fistula, or a recent episode (within 6 months) of intestinal ischemia or ischemic colitis.
Contraindication to oral/enteral therapy at randomization (e.g., severe reflux, severe nausea/vomiting, or bowel obstruction).
White blood cell count >15.0 × 10⁹ cells/L within 7 days prior to randomization.
Absolute neutrophil count (ANC) <0.5 × 10⁹ cells/L on two consecutive occasions within 7 days prior to randomization, or persistent ANC <1.0 × 10⁹ cells/L.
Receipt of bezlotoxumab during the standard-of-care antibiotic treatment course for the qualifying CDI episode.
Use of antidiarrheal agents (e.g., loperamide, diphenoxylate) within 3 days prior to the first dose of study drug.
Expected need for oral or parenteral antibiotic therapy for non-CDI indications from randomization through Week 24 (end of study).
History of malignancy within 2 months prior to randomization, with receipt of chemotherapy or other treatments known to cause gastrointestinal adverse effects.
Receipt of any investigational drug or vaccine within 30 days prior to randomization.
Current or anticipated need for mechanical ventilation or vasopressor support for hemodynamic stabilization.
Life expectancy <3 months.
Major gastrointestinal surgery (e.g., large bowel resection or diversion procedure) within 3 months prior to randomization; current ileostomy; or prior total colectomy.
Participants with a history of appendectomy, cholecystectomy, or bariatric surgery (e.g., gastric banding) may be eligible upon discussion with the medical monitor, provided the procedure was completed at least 1 month before randomization and the participant has fully recovered.
Pregnant or breastfeeding.
Known hypersensitivity, allergy, or intolerance to any component of the VE303 formulation.
Any clinically significant or uncontrolled medical or surgical condition not specified above that, in the investigator’s opinion, could interfere with study drug administration, the interpretation of safety or efficacy results, or compromise participant safety or well-being.
The Estimated Number of Participants
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Taiwan
6 participants
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Global
852 participants
