Clinical Trials List
Protocol NumberVE303-003
Not yet recruiting
2025-04-01 - 2027-11-30
Recruiting3
A randomized, double-blind, placebo-controlled phase 3 trial is investigating the use of VE303 for the prevention of recurrent Clostridium difficile infection.
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Trial Applicant
PAREXEL INTERNATIONAL CO., LTD.
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Sponsor
Parexel International Co., Ltd.
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Trial scale
Multi-Regional Multi-Center
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Update
2026/08/10
Investigators and Locations
Co-Principal Investigator
- Ho Mao-Wang 無
- 蘇浤傑 無
- 鄭孟瑜 Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Fang-Jung Yu Yu Division of Infectious Disease
- 呂其融 Division of Infectious Disease
- Chun-Yuan Lee Division of Infectious Disease
- Shang-Yi Lin Division of Infectious Disease
- Chun-Yu Lin Division of Infectious Disease
- Wen-Hung Hsu Division of Infectious Disease
- Tun-Chieh Chen Division of Infectious Disease
- Chung-Hao Huang Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Cheng-Hsun Chiu
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Double-blind, placebo-controlled trial: Proportion of participants with laboratory-confirmed CDI recurrence by week 8
Objectives
The overall objective of the RESTORATiVE303 trial was to evaluate the safety and relapse rate of Clostridium difficile infection (CDI) at week 8 in participants receiving a 14-day course of VE303 or the equivalent placebo. The objectives and endpoints of Phase 1 (relapsed CDI) and Phase 2 (high-risk primary CDI) were identical. However, the endpoints from Phase 1 and Phase 2 of the trial will be assessed and analyzed separately.
Test Drug
VE303
Active Ingredient
VE303
Dosage Form
Capsules
Dosage
2.7 × 10^9 CFU
Endpoints
Double-blind, placebo-controlled trial: Proportion of participants with laboratory-confirmed CDI recurrence by week 8
Inclution Criteria
Phase 1 Inclusion (Recurrent Clostridium difficile infection (rCDI) population):
1. Age ≥ 12 years (in countries allowing adolescent inclusion) and ≥ 18 years (in other countries) with a laboratory-confirmed qualifying episode of Clostridium difficile infection and a history of at least one previous Clostridium difficile infection within the past 6 months.
Phase 2 Inclusion (High-Risk Primary Clostridium difficile infection (pCDI-hr) population):
2. Age ≥ 75 years with a laboratory-confirmed qualifying episode of Clostridium difficile infection or
3. Age 12 to 74 years (in countries allowing adolescent inclusion) and 18 to 74 years (in other countries) with a laboratory-confirmed qualifying episode of Clostridium difficile infection and at least two of the following risk factors:
– Age ≥ 65 years
– Renal dysfunction, defined as an estimated creatinine clearance < 60 mL/min/1.73 m² at the time of a qualifying Clostridium difficile infection episode
– Past 2 – History of regular proton pump inhibitor (PPI) use within the past month, and expected to continue PPI use during the trial
– History of Clostridium difficile infection episodes within the 6 to 12 months prior to enrollment
– Immunosuppression due to pre-existing disease or its treatment
– Solid organ or hematopoietic bone marrow stem cell transplantation
For Phase 1 or Phase 2 enrollment:
4. Eligible CDI events must meet all of the following criteria:
a. ≥ 3 new unformed bowel movements (i.e., Bristol Stool Scale categories 5 to 7) for at least 2 consecutive days within 24 hours
b. Onset of CDI symptoms within 4 weeks prior to initiation of SoC antibiotic therapy for CDI
c. A stool sample collected before (or no more than 72 hours after) initiation of SoC antibiotic therapy that is positive for CDI in a laboratory, defined as EIA and GDH of toxin A/B (if GDH/EIA) by a local or central laboratory. (If toxin results are inconsistent, PCR reflection testing will be performed.)
d. Diarrhea deemed unlikely to have other causes
5. Before receiving the investigational drug, participants should:
a. Receive and complete a course of SoC antibiotics for at least 10 days and at most 28 days (Note: The choice of SoC drug is determined by the physician, and the antibiotic dose should not be gradually reduced.)
b. Meet the criteria for a successful clinical response, defined as symptom control of a qualifying CDI event, i.e., <3 loose/unformed bowel movements per 24 hours for at least 2 consecutive days.
6. For women of fertility, pregnancy tests must be negative, and pregnancy must be confirmed within a maximum of 3 days during the trial and after the last dose of the investigational drug. For one month, the patient agrees to use a highly effective and acceptable form of contraception (a highly effective contraception is defined as a method with an annual failure rate of less than 1% when used correctly and consistently, such as adding a barrier method to an existing hormonal contraception, hormonal contraception related to ovulation suppression, including implants, injections, and oral contraceptives, and some intrauterine devices), abstain from sexual activity, or have sexual intercourse only with a female partner and/or a medically confirmed successful vasectomy. Abstinence is defined as avoiding heterosexual intercourse throughout the entire risk period associated with the trial treatment. The reliability of abstinence must be assessed based on the clinical trial, the patient's preferences, and their usual lifestyle. Periodic abstinence (cycle method, symptom-basal body temperature method, post-ovulation contraception), withdrawal (coitus interruptus), spermicide alone, and lactational amenorrhea are not acceptable methods of contraception.
7. Able to receive the first dose of investigational drug on the last scheduled date of SoC antibiotic administration for a qualifying CDI event, or within two days after completion of antibiotic administration.
8. Has recovered from any complications of a severe or fulminant CDI and achieved clinical stability at the time of randomization.
9. Able and willing to comply with trial assessments (e.g., able to swallow oral capsules, cooperate with trial follow-up visits and procedures, provide blood and stool samples, and complete questionnaires).
10. Able and willing to provide written consent/a written consent form before initiating any trial-specific procedures or administration of the investigational drug, and understand the potential risks and benefits of trial inclusion and administration of the investigational drug. Informed consent may be provided by a legal guardian (LAR) where appropriate. For participants under the legal age of majority (18 years in most areas), the consent form should be signed by the participant's legal guardian or jointly signed with them, using a child-specific consent form to comply with local regulations and practices.
1. Age ≥ 12 years (in countries allowing adolescent inclusion) and ≥ 18 years (in other countries) with a laboratory-confirmed qualifying episode of Clostridium difficile infection and a history of at least one previous Clostridium difficile infection within the past 6 months.
Phase 2 Inclusion (High-Risk Primary Clostridium difficile infection (pCDI-hr) population):
2. Age ≥ 75 years with a laboratory-confirmed qualifying episode of Clostridium difficile infection or
3. Age 12 to 74 years (in countries allowing adolescent inclusion) and 18 to 74 years (in other countries) with a laboratory-confirmed qualifying episode of Clostridium difficile infection and at least two of the following risk factors:
– Age ≥ 65 years
– Renal dysfunction, defined as an estimated creatinine clearance < 60 mL/min/1.73 m² at the time of a qualifying Clostridium difficile infection episode
– Past 2 – History of regular proton pump inhibitor (PPI) use within the past month, and expected to continue PPI use during the trial
– History of Clostridium difficile infection episodes within the 6 to 12 months prior to enrollment
– Immunosuppression due to pre-existing disease or its treatment
– Solid organ or hematopoietic bone marrow stem cell transplantation
For Phase 1 or Phase 2 enrollment:
4. Eligible CDI events must meet all of the following criteria:
a. ≥ 3 new unformed bowel movements (i.e., Bristol Stool Scale categories 5 to 7) for at least 2 consecutive days within 24 hours
b. Onset of CDI symptoms within 4 weeks prior to initiation of SoC antibiotic therapy for CDI
c. A stool sample collected before (or no more than 72 hours after) initiation of SoC antibiotic therapy that is positive for CDI in a laboratory, defined as EIA and GDH of toxin A/B (if GDH/EIA) by a local or central laboratory. (If toxin results are inconsistent, PCR reflection testing will be performed.)
d. Diarrhea deemed unlikely to have other causes
5. Before receiving the investigational drug, participants should:
a. Receive and complete a course of SoC antibiotics for at least 10 days and at most 28 days (Note: The choice of SoC drug is determined by the physician, and the antibiotic dose should not be gradually reduced.)
b. Meet the criteria for a successful clinical response, defined as symptom control of a qualifying CDI event, i.e., <3 loose/unformed bowel movements per 24 hours for at least 2 consecutive days.
6. For women of fertility, pregnancy tests must be negative, and pregnancy must be confirmed within a maximum of 3 days during the trial and after the last dose of the investigational drug. For one month, the patient agrees to use a highly effective and acceptable form of contraception (a highly effective contraception is defined as a method with an annual failure rate of less than 1% when used correctly and consistently, such as adding a barrier method to an existing hormonal contraception, hormonal contraception related to ovulation suppression, including implants, injections, and oral contraceptives, and some intrauterine devices), abstain from sexual activity, or have sexual intercourse only with a female partner and/or a medically confirmed successful vasectomy. Abstinence is defined as avoiding heterosexual intercourse throughout the entire risk period associated with the trial treatment. The reliability of abstinence must be assessed based on the clinical trial, the patient's preferences, and their usual lifestyle. Periodic abstinence (cycle method, symptom-basal body temperature method, post-ovulation contraception), withdrawal (coitus interruptus), spermicide alone, and lactational amenorrhea are not acceptable methods of contraception.
7. Able to receive the first dose of investigational drug on the last scheduled date of SoC antibiotic administration for a qualifying CDI event, or within two days after completion of antibiotic administration.
8. Has recovered from any complications of a severe or fulminant CDI and achieved clinical stability at the time of randomization.
9. Able and willing to comply with trial assessments (e.g., able to swallow oral capsules, cooperate with trial follow-up visits and procedures, provide blood and stool samples, and complete questionnaires).
10. Able and willing to provide written consent/a written consent form before initiating any trial-specific procedures or administration of the investigational drug, and understand the potential risks and benefits of trial inclusion and administration of the investigational drug. Informed consent may be provided by a legal guardian (LAR) where appropriate. For participants under the legal age of majority (18 years in most areas), the consent form should be signed by the participant's legal guardian or jointly signed with them, using a child-specific consent form to comply with local regulations and practices.
Exclusion Criteria
1. A history of prolonged diarrhea unrelated to Clostridium difficile infection (defined as ≥3 loose stools per day for at least 4 weeks) within the 3 months prior to randomization.
2. Infectious diarrhea (including bacterial, viral, or parasitic causes) other than a confirmed CDI during an eligible CDI episode.
3. Known or suspected toxic megacolon or small bowel obstruction at the time of randomization.
4. Confirmed history of colonic disease, inflammatory bowel disease, microscopic colitis, short bowel syndrome, gastrointestinal (GI) fistula, or recent (within 6 months prior to screening) episode of intestinal ischemia or ischemic colitis.
5. Contraindications to oral/enteral therapy at the time of randomization (e.g., severe reflux, severe nausea/vomiting, or bowel obstruction).
6. White blood cell count > 15.0 x 10⁹ cells/L within 7 days prior to randomization.
7. Absolute neutrophil count (ANC) < 0.5 x 10⁹ cells/L for two consecutive days within 7 days prior to randomization, or an absolute neutrophil count consistently < 1.0 x 10⁹ cells/L.
8. Received bezlotoxumab during standard care antibiotic treatment for an eligible Clostridium difficile infection episode.
9. Scheduled to receive the first dose of investigational drug 3 days prior to randomization. 10. Expected to receive oral or parenteral antibiotic therapy for non-difficult Clostridium difficile infection between randomization and week 24 (end of trial).
11. History of malignancy within 2 months prior to randomization, and receiving chemotherapy or other treatments known to cause gastrointestinal adverse reactions.
12. Received any investigational drug or vaccine within 30 days prior to randomization.
13. Currently or likely to receive mechanical ventilation or vasopressors for hemodynamic support.
14. Expected life expectancy < 3 months.
15. Underwent major gastrointestinal surgery (e.g., major bowel resection or shunt), is currently undergoing ileostomy, or has previously undergone total colectomy within 3 months prior to randomization. Participants who have undergone appendectomy, cholecystectomy, or gastric reduction surgery (e.g., gastric banding) may be included in the trial after discussion with the medical monitor, provided the surgery was performed at least one month prior to randomization and the participant has fully recovered.
16. Pregnancy or breastfeeding
17. Known allergic reaction/allergy/intolerance to any component of the VE303 test formulation.
18. Clinically significant or poorly controlled medical or surgical conditions not mentioned above may, in the opinion of the trial administrator, interfere with the administration of the investigational drug, the interpretation of trial safety and efficacy data, or compromise the safety or well-being of participants.
2. Infectious diarrhea (including bacterial, viral, or parasitic causes) other than a confirmed CDI during an eligible CDI episode.
3. Known or suspected toxic megacolon or small bowel obstruction at the time of randomization.
4. Confirmed history of colonic disease, inflammatory bowel disease, microscopic colitis, short bowel syndrome, gastrointestinal (GI) fistula, or recent (within 6 months prior to screening) episode of intestinal ischemia or ischemic colitis.
5. Contraindications to oral/enteral therapy at the time of randomization (e.g., severe reflux, severe nausea/vomiting, or bowel obstruction).
6. White blood cell count > 15.0 x 10⁹ cells/L within 7 days prior to randomization.
7. Absolute neutrophil count (ANC) < 0.5 x 10⁹ cells/L for two consecutive days within 7 days prior to randomization, or an absolute neutrophil count consistently < 1.0 x 10⁹ cells/L.
8. Received bezlotoxumab during standard care antibiotic treatment for an eligible Clostridium difficile infection episode.
9. Scheduled to receive the first dose of investigational drug 3 days prior to randomization. 10. Expected to receive oral or parenteral antibiotic therapy for non-difficult Clostridium difficile infection between randomization and week 24 (end of trial).
11. History of malignancy within 2 months prior to randomization, and receiving chemotherapy or other treatments known to cause gastrointestinal adverse reactions.
12. Received any investigational drug or vaccine within 30 days prior to randomization.
13. Currently or likely to receive mechanical ventilation or vasopressors for hemodynamic support.
14. Expected life expectancy < 3 months.
15. Underwent major gastrointestinal surgery (e.g., major bowel resection or shunt), is currently undergoing ileostomy, or has previously undergone total colectomy within 3 months prior to randomization. Participants who have undergone appendectomy, cholecystectomy, or gastric reduction surgery (e.g., gastric banding) may be included in the trial after discussion with the medical monitor, provided the surgery was performed at least one month prior to randomization and the participant has fully recovered.
16. Pregnancy or breastfeeding
17. Known allergic reaction/allergy/intolerance to any component of the VE303 test formulation.
18. Clinically significant or poorly controlled medical or surgical conditions not mentioned above may, in the opinion of the trial administrator, interfere with the administration of the investigational drug, the interpretation of trial safety and efficacy data, or compromise the safety or well-being of participants.
The Estimated Number of Participants
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Taiwan
6 participants
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Global
852 participants
