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TerminatedNCT01887912Updated Mar 28, 2022Results posted

Study of a Candidate Clostridium Difficile Toxoid Vaccine in Subjects at Risk for C. Difficile Infection

A Phase 3 interventional study of C. difficile Toxoid Vaccine and Placebo: 0.9% normal saline in Clostridium Difficile Infection, sponsored by Sanofi Pasteur, a Sanofi Company. Terminated at 335 sites in 26 countries. Open to participants aged 50 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-03-28.

Sponsored by Sanofi Pasteur, a Sanofi Company · Phase 3, Interventional, and Prevention

Why this study was terminated
The Independent Data Monitoring Committee (IDMC) concluded that the probability that the study will meet its primary objective is low.
Phase
Phase 3
Study type
Interventional
Enrollment
9,302
Allocation
Randomized
Ages
50 Years and older
Sex
All
01

Study summary

The aim of this study was to evaluate the efficacy of the Clostridium difficile vaccine to prevent primary symptomatic C. difficile infection (CDI) in participants at risk for CDI where there is a substantial unmet medical need.

Primary objective:

  • To assess the efficacy of the C. difficile vaccine in preventing the onset of symptomatic primary CDI confirmed by polymerase chain reaction (PCR) in adult participants aged >= 50 years who are at risk for CDI and have received at least 1 injection.

Secondary Objectives:

Efficacy:

  • To assess prevention of symptomatic PCR-confirmed primary CDI cases after 3 injections administered at 0, 7, and 30 days.
  • To assess prevention of symptomatic PCR-confirmed primary CDI cases after completion of at least 2 injections.

Immunogenicity:

  • To describe the immunogenicity to toxin A and toxin B at specific time points in a subset of participant and in participants with CDI at Day 0 and Day 60.

Safety:

  • To describe the safety profile of all participants who received at least 1 injection.
Read the detailed description

The study was designed as an event-driven group sequential protocol with 4 interim analyses at defined information milestones and a final analysis when a specific number of clinical endpoints are reached. Analyses of trial futility (non-efficacy) were to be performed at the first 2 interim analyses, and the study was to be stopped if either of those analyses provided robust and compelling evidence that meaningful levels of vaccine efficacy (VE) would not be demonstrated.

Following completion of the first interim analysis (50 cases of confirmed CDI observed), the futility criterion was met and in accordance with IDMC recommendation, enrollment and further vaccination ceased in November 2017.

Due to the early termination of the study, some of the planned secondary efficacy endpoints could not be analyzed as all planned data were not collected.

Participants were randomized to receive either the candidate vaccine or a placebo that was to be administered in a 3-dose schedule. At the time of group assignment, 928 participants (10% of total enrollment) were randomized to an immunogenicity subset; and 1859 participants (20% of total enrollment) were randomized to a reactogenicity subset.

Safety was assessed in all participants in terms of unsolicited adverse events from Day 0 to Day 60, as well as serious adverse events (SAEs) throughout the study. Solicited adverse reactions were collected for 6 days following each injection in the reactogenicity subset.

02

Conditions studied

  • Clostridium Difficile Infection

Keywords

  • Clostridium difficile Toxoid Vaccine
  • Clostridium difficile infection
  • Cdiffense
03

In context

Infections

6,687 studies on the registry are indexed under Infections; 807 are open to participants now.

This study's enrollment of 9,302 is above the median of 120 across 4,200 interventional studies indexed under Infections.

Browse Infections studies →

Lead sponsor

Sanofi Pasteur, a Sanofi Company is the lead sponsor of 366 studies on the registry; 4 are open to participants now.

Of its 94 completed or terminated interventional studies of FDA-regulated products, 73 (78%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
50 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Aged >= 50 years on the day of inclusion
  • Informed consent form had been signed and dated.
  • Attended all scheduled visits and complied with all trial procedures.
  • Covered by health insurance (if required).
  • Must fulfill at least 1 of the following criteria

Risk Stratum 1:

  • Had at least 2 hospital stays, each lasting at least >= 24 hours, in the 12 months before enrollment, and
  • Had received systemic (not topical) antibiotics in the 12 months before enrollment, or

Risk Stratum 2:

  • Was anticipated to have an in-patient hospitalization for a planned surgical procedure within 60 days of enrollment. The impending hospital stay was planned to be >= 72 hours for a surgery involving 1 of the following:
  • Kidney/bladder/urinary system
  • Musculoskeletal system
  • Respiratory system
  • Circulatory system
  • Central nervous system.

Exclusion criteria

Exclusion Criteria:

  • Participant was pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and until at least 4 weeks after the last vaccination).
  • Participation in the 4 weeks preceding the first trial vaccination or participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.
  • Receipt of any vaccine in the 4 weeks preceding the first trial vaccination except for influenza (seasonal or pandemic) and pneumococcal vaccines. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines.
  • Previous vaccination against C. difficile with either the trial vaccine, another vaccine, or monoclonal antibodies.
  • Diarrhea on day of enrollment.
  • Self-reported current or prior CDI episode.
  • Anticipated or current receipt of kidney dialysis treatment.
  • History of gastrointestinal surgery for gastrointestinal malignancy (Note: Colonoscopy, polypectomy, and appendectomy are not exclusion criteria).
  • History of inflammatory bowel disease, irritable bowel syndrome (must include diarrhea as a symptom), colostomy, or small or large intestine bowel surgery where resection was performed.
  • Receiving enteral feeding (e.g., nasogastric, gastrostomy, and jejunostomy tube feeding).
  • Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
  • Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances.
  • Self-reported thrombocytopenia, contraindicating intramuscular vaccination.
  • Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
  • Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures in the opinion of the Investigator.
  • Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion.
  • Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature >= 38.0 degree Celsius [>= 100.4°Fahrenheit]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.
  • Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.
05

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
9,302 participants (actual)

Study arms

  • Experimental
    C. difficile Vaccine Group

    Participants received 1 injection of 0.5 mL C. difficile toxoid vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).

    Biological: C. difficile Toxoid Vaccine

  • Placebo comparator
    Placebo Group

    Participants received 1 injection of 0.5 mL placebo matched to vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).

    Biological: Placebo: 0.9% normal saline

Interventions

  • BiologicalC. difficile Toxoid Vaccine

    0.5 mL, Intramuscular

  • BiologicalPlacebo: 0.9% normal saline

    0.5 mL, Intramuscular

06

What researchers measure

Primary outcomes

  1. Number of Participants With Symptomatic Polymerase Chain Reaction (PCR)-Confirmed Primary C. Difficile Infection (CDI) Cases

    Symptomatic PCR-confirmed CDI cases were defined as the number of participants with combination of clinical and laboratory findings. Clinical components were: \>= 3 loose stools in \<= 24 hours, loose stools (defined as type 6 \[fluffy pieces with ragged edges, mushy\] or type 7 \[watery, no solid pieces\] according to the Bristol Stool Chart) lasting \>= 24 hours. Laboratory findings were: stool sample positive for C. difficile Toxin B by PCR at central laboratory or diagnosis of pseudomembranous colitis visualized at colonoscopy.

    Time frame: Up to 3 years post injection 1

Secondary outcomes

  1. Number of Participants With Severe PCR-Confirmed Primary CDI Cases

    Severe CDI cases were defined as number of participants with at least one of the following symptoms: fever \>= 38.5 degree Celsius (°C), white blood cell count \>= 15,000 cells/mm\^3, ileus, pseudomembranous colitis, serum albumin \<3 gram per deciliter, abdominal distension, abdominal tenderness, or admission to the intensive care unit within 7 days of CDI diagnosis.

    Time frame: Up to 3 years post injection 1

  2. Number of Participants With Loose Stool Episodes

    Loose stools were defined as type 6 (fluffy pieces with ragged edges, mushy) or type 7 (watery, no solid pieces) according to the Bristol Stool Chart. In this outcome measure, participants with number of loose stool episodes (categorized as: loose stool episodes less than 3, 3 to 6, 7 to 10, 11 to 15 and greater than 15) were reported.

    Time frame: Up to 3 years post injection 1

  3. Number of Participants With Symptomatic PCR Confirmed CDI Cases: Per-Protocol Population

    Symptomatic PCR confirmed CDI cases were defined as the number of participants with combination of clinical and laboratory findings. Clinical components were: \>= 3 loose stools in \<= 24 hours, loose stools (defined as type 6 \[fluffy pieces with ragged edges, mushy\] or type 7 \[watery, no solid pieces\] according to the Bristol Stool Chart) lasting \>= 24 hours. Laboratory findings were: stool sample positive for C. difficile Toxin B by PCR at central laboratory or diagnosis of pseudomembranous colitis visualized at colonoscopy. Analysis was performed on per-protocol efficacy analysis set (PPEAS).

    Time frame: Up to 3 years post injection 1

  4. Serum Antibody Concentrations Against Toxins A and B Measured by Enzyme-Linked Immunosorbent Assay (ELISA)

    Serum antibody concentrations against toxins A and B were measured by ELISA and expressed as geometric mean concentration (GMC). The 2-sided 95% Confidence Interval (CI) of GMC was based on the Student t-distribution. Analysis was performed on Per Protocol Immunogenicity Analysis Set, which included participants who had at least 1 injection, no relevant protocol deviations (not met inclusion criteria/ met exclusion criteria, not received vaccine/ not received in proper time window, received different vaccine than randomized, preparation and/ or administration of vaccine not per protocol, protocol-restricted therapy, not provided post-dose serology sample/serology sample did not produced a valid test result).

    Time frame: Day 0, Day 14, Day 30, Day 60, Day 210, Day 390, Day 570, Day 750, Day 930, and Day 1110

  5. Percentage of Participants With >= 2 and 4-Fold Rise in Serum Antibody Concentrations From Baseline Against Toxins A and B Measured by ELISA

    Percentage of Participants with \>= 2 and 4-fold rise in serum antibody concentrations against toxins A and B were measured by ELISA. The 2-sided 95% Cl of the percentage was based on Exact method calculations.

    Time frame: Day 60

  6. Serum Antibody Concentrations Against Toxins A and B Measured by ELISA in Participants With CDI

    Serum antibody concentrations against toxins A and B were measured by ELISA and expressed as GMC. The 2-sided 95% CI GMC was based on the Student t-distribution. Symptomatic PCR-confirmed CDI cases were defined as the number of participants with combination of clinical and laboratory findings. Clinical components were: \>= 3 loose stools in \<= 24 hours, loose stools (defined as type 6 \[fluffy pieces with ragged edges, mushy\] or type 7 \[watery, no solid pieces\] according to the Bristol Stool Chart) lasting \>= 24 hours. Laboratory findings were: stool sample positive for C. difficile Toxin B by PCR at central laboratory or diagnosis of pseudomembranous colitis visualized at colonoscopy.

    Time frame: Day 0 and Day 60

  7. Serum Antibody Concentrations Against Toxins A and B Measured by Toxin Neutralization Assay (TNA)

    Serum antibody concentrations against toxins A and B were measured by TNA and expressed as geometric mean titer (GMT). The 2-sided 95% Cl of GMT was based on the Student t-distribution.

    Time frame: Day 0, Day 14, Day 30, Day 60, Day 210, Day 390, Day 570, Day 750, Day 930, and Day 1110

  8. Percentage of Participants With >= 2 and 4-Fold Rise in Serum Antibody Concentrations From Baseline Against Toxins A and B Measured by TNA

    Percentage of Participants with \>= 2 and 4-fold rise in serum antibody concentrations against toxins A and B were measured by TNA. The 2-sided 95% CI of the percentage was based on Exact method calculations.

    Time frame: Day 60

  9. Serum Antibody Concentrations Against Toxins A and B Measured by TNA in Participants With CDI

    Serum antibody concentrations against toxins A and B were measured by TNA and were expressed as GMT. The 2-sided 95% CI GMC was based on the Student t-distribution. Symptomatic PCR confirmed CDI cases were defined as the number of participants with combination of clinical and laboratory findings. Clinical components were: \>= 3 loose stools in \<= 24 hours, loose stools (defined as type 6 \[fluffy pieces with ragged edges, mushy\] or type 7 \[watery, no solid pieces\] according to the Bristol Stool Chart) lasting \>= 24 hours. Laboratory findings were: stool sample positive for C. difficile Toxin B by PCR at central laboratory or diagnosis of pseudomembranous colitis visualized at colonoscopy.

    Time frame: Day 0 and Day 60

  10. Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions

    Solicited injection site reactions: pain, erythema, and swelling. Pain: Grade 1: no interference with activity, Grade 2: some interference with activity, Grade 3: significant; prevents daily activity; Erythema and swelling: Grade 1: \>= 25 to \<=50 mm, Grade 2: \>51 to \<=100 mm, Grade 3: \>100 mm. Solicited systemic reactions: fever, headache, malaise, myalgia, and arthralgia. Fever: Grade 1: \>= 38.0°C to \<=38.4°C or \>= 100.4° Fahrenheit (F) to \<=101.1°F, Grade 2: \>=38.5°C to \<= 38.9°C or \>=101.2°F to \<=102.0°F, Grade 3: \>=39.0°C or \>=102.1°F. Headache, malaise, and myalgia: Grade 1: no interference with activity, Grade 2: some interference with activity, Grade 3: significant; prevents daily activity; Arthralgia: Grade 1: free range of motion but complains of pain or discomfort, Grade 2: decreased range of motion due to pain or discomfort, Grade 3: unwilling to move due to pain.

    Time frame: Day 0 to Day 6 after any vaccination

07

Results

Posted Jul 5, 2019

Participant flow

Study participants were enrolled in the study from 30 July 2013 to 17 November 2017.

Participant flow — Overall Study
MilestoneC. Difficile Vaccine GroupPlacebo Group
Started62013101
Safety population61133057
Completed48092370
Not completed1392731
Withdrew: Serious adverse event400198
Withdrew: Other adverse event3415
Withdrew: Protocol violation6737
Withdrew: Lost to follow-up16374
Withdrew: Withdrawal by subject606349
Withdrew: Other12258

Outcome measures

PrimaryNumber of Participants With Symptomatic Polymerase Chain Reaction (PCR)-Confirmed Primary C. Difficile Infection (CDI) Cases

Symptomatic PCR-confirmed CDI cases were defined as the number of participants with combination of clinical and laboratory findings. Clinical components were: \>= 3 loose stools in \<= 24 hours, loose stools (defined as type 6 \[fluffy pieces with ragged edges, mushy\] or type 7 \[watery, no solid pieces\] according to the Bristol Stool Chart) lasting \>= 24 hours. Laboratory findings were: stool sample positive for C. difficile Toxin B by PCR at central laboratory or diagnosis of pseudomembranous colitis visualized at colonoscopy.

Time frame:
Up to 3 years post injection 1
Reported as:
Count of participants · Participants
Number of Participants With Symptomatic Polymerase Chain Reaction (PCR)-Confirmed Primary C. Difficile Infection (CDI) Cases
ParticipantsC. Difficile Vaccine GroupPlacebo Group
Number of Participants With Symptomatic Polymerase Chain Reaction (PCR)-Confirmed Primary C. Difficile Infection (CDI) Cases3416
SecondaryNumber of Participants With Severe PCR-Confirmed Primary CDI Cases

Severe CDI cases were defined as number of participants with at least one of the following symptoms: fever \>= 38.5 degree Celsius (°C), white blood cell count \>= 15,000 cells/mm\^3, ileus, pseudomembranous colitis, serum albumin \<3 gram per deciliter, abdominal distension, abdominal tenderness, or admission to the intensive care unit within 7 days of CDI diagnosis.

Time frame:
Up to 3 years post injection 1
Reported as:
Count of participants · Participants
Number of Participants With Severe PCR-Confirmed Primary CDI Cases
ParticipantsC. Difficile Vaccine GroupPlacebo Group
Number of Participants With Severe PCR-Confirmed Primary CDI Cases96
SecondaryNumber of Participants With Loose Stool Episodes

Loose stools were defined as type 6 (fluffy pieces with ragged edges, mushy) or type 7 (watery, no solid pieces) according to the Bristol Stool Chart. In this outcome measure, participants with number of loose stool episodes (categorized as: loose stool episodes less than 3, 3 to 6, 7 to 10, 11 to 15 and greater than 15) were reported.

Time frame:
Up to 3 years post injection 1
Reported as:
Count of participants · Participants
Number of Participants With Loose Stool Episodes
ParticipantsC. Difficile Vaccine GroupPlacebo Group
<300
3 to 674
7 to 1072
11 to 1574
>15136
SecondaryNumber of Participants With Symptomatic PCR Confirmed CDI Cases: Per-Protocol Population

Symptomatic PCR confirmed CDI cases were defined as the number of participants with combination of clinical and laboratory findings. Clinical components were: \>= 3 loose stools in \<= 24 hours, loose stools (defined as type 6 \[fluffy pieces with ragged edges, mushy\] or type 7 \[watery, no solid pieces\] according to the Bristol Stool Chart) lasting \>= 24 hours. Laboratory findings were: stool sample positive for C. difficile Toxin B by PCR at central laboratory or diagnosis of pseudomembranous colitis visualized at colonoscopy. Analysis was performed on per-protocol efficacy analysis set (PPEAS).

Time frame:
Up to 3 years post injection 1
Reported as:
Count of participants · Participants
Number of Participants With Symptomatic PCR Confirmed CDI Cases: Per-Protocol Population
ParticipantsC. Difficile Vaccine GroupPlacebo Group
Number of Participants With Symptomatic PCR Confirmed CDI Cases: Per-Protocol Population2313
SecondarySerum Antibody Concentrations Against Toxins A and B Measured by Enzyme-Linked Immunosorbent Assay (ELISA)

Serum antibody concentrations against toxins A and B were measured by ELISA and expressed as geometric mean concentration (GMC). The 2-sided 95% Confidence Interval (CI) of GMC was based on the Student t-distribution. Analysis was performed on Per Protocol Immunogenicity Analysis Set, which included participants who had at least 1 injection, no relevant protocol deviations (not met inclusion criteria/ met exclusion criteria, not received vaccine/ not received in proper time window, received different vaccine than randomized, preparation and/ or administration of vaccine not per protocol, protocol-restricted therapy, not provided post-dose serology sample/serology sample did not produced a valid test result).

Time frame:
Day 0, Day 14, Day 30, Day 60, Day 210, Day 390, Day 570, Day 750, Day 930, and Day 1110
Reported as:
Geometric mean · ELISA units per milliliter (EU/mL)
Serum Antibody Concentrations Against Toxins A and B Measured by Enzyme-Linked Immunosorbent Assay (ELISA)
ELISA units per milliliter (EU/mL)C. Difficile Vaccine GroupPlacebo Group
Toxin A ImunnoglobulinG (IgG): Day 00.957 (0.897 to 1.02)0.999 (0.912 to 1.09)
Toxin A IgG: Day 143.19 (2.68 to 3.80)0.913 (0.849 to 0.983)
Toxin A IgG: Day 3012.2 (10.4 to 14.3)0.959 (0.889 to 1.03)
Toxin A IgG: Day 6043.7 (38.1 to 50.2)0.933 (0.867 to 1.00)
Toxin A IgG: Day 21012.0 (10.5 to 13.8)0.944 (0.865 to 1.03)
Toxin A IgG: Day 3906.02 (5.23 to 6.93)0.955 (0.856 to 1.06)
Toxin A IgG: Day 5704.50 (3.86 to 5.25)0.908 (0.834 to 0.989)
Toxin A IgG: Day 7504.02 (3.38 to 4.78)0.856 (0.776 to 0.944)
Toxin A IgG: Day 9303.83 (3.02 to 4.85)0.902 (0.796 to 1.02)
Toxin A IgG: Day 11103.75 (2.64 to 5.34)1.09 (0.786 to 1.50)
Toxin B IgG: Day 01.40 (1.24 to 1.57)1.49 (1.24 to 1.79)
Toxin B IgG: Day 144.36 (3.37 to 5.64)1.56 (1.29 to 1.89)
Toxin B IgG: Day 3010.0 (7.85 to 12.8)1.46 (1.21 to 1.75)
Toxin B IgG: Day 6024.8 (20.1 to 30.6)1.42 (1.18 to 1.71)
Toxin B IgG: Day 2106.62 (5.36 to 8.19)1.31 (1.07 to 1.61)
Toxin B IgG: Day 3903.98 (3.15 to 5.02)1.24 (0.991 to 1.56)
Toxin B IgG: Day 5703.37 (2.63 to 4.32)1.15 (0.905 to 1.47)
Toxin B IgG: Day 7502.86 (2.14 to 3.84)1.11 (0.840 to 1.47)
Toxin B IgG: Day 9302.42 (1.65 to 3.55)1.13 (0.812 to 1.58)
Toxin B IgG: Day 11103.46 (2.06 to 5.81)0.966 (0.592 to 1.58)
SecondaryPercentage of Participants With >= 2 and 4-Fold Rise in Serum Antibody Concentrations From Baseline Against Toxins A and B Measured by ELISA

Percentage of Participants with \>= 2 and 4-fold rise in serum antibody concentrations against toxins A and B were measured by ELISA. The 2-sided 95% Cl of the percentage was based on Exact method calculations.

Time frame:
Day 60
Reported as:
Number · percentage of participants
Percentage of Participants With >= 2 and 4-Fold Rise in Serum Antibody Concentrations From Baseline Against Toxins A and B Measured by ELISA
percentage of participantsC. Difficile Vaccine GroupPlacebo Group
Toxin A IgG: >=293.3 (90.5 to 95.5)0.9 (0.1 to 3.3)
Toxin A IgG: >=488.9 (85.6 to 91.7)0.0 (0.0 to 1.7)
Toxin B IgG: >=282.2 (78.3 to 85.7)4.6 (2.2 to 8.3)
Toxin B IgG: >=473.2 (68.8 to 77.3)0.5 (0.0 to 2.5)
SecondarySerum Antibody Concentrations Against Toxins A and B Measured by ELISA in Participants With CDI

Serum antibody concentrations against toxins A and B were measured by ELISA and expressed as GMC. The 2-sided 95% CI GMC was based on the Student t-distribution. Symptomatic PCR-confirmed CDI cases were defined as the number of participants with combination of clinical and laboratory findings. Clinical components were: \>= 3 loose stools in \<= 24 hours, loose stools (defined as type 6 \[fluffy pieces with ragged edges, mushy\] or type 7 \[watery, no solid pieces\] according to the Bristol Stool Chart) lasting \>= 24 hours. Laboratory findings were: stool sample positive for C. difficile Toxin B by PCR at central laboratory or diagnosis of pseudomembranous colitis visualized at colonoscopy.

Time frame:
Day 0 and Day 60
Reported as:
Geometric mean · EU/mL
Serum Antibody Concentrations Against Toxins A and B Measured by ELISA in Participants With CDI
EU/mLC. Difficile Vaccine GroupPlacebo Group
Toxin A IgG: Day 01.15 (0.821 to 1.62)1.04 (0.661 to 1.64)
Toxin A IgG: Day 6042.1 (18.0 to 98.3)1.06 (0.632 to 1.76)
Toxin B IgG: Day 01.41 (0.762 to 2.62)1.05 (0.504 to 2.20)
Toxin B IgG: Day 6019.3 (6.65 to 56.2)1.13 (0.609 to 2.11)
SecondarySerum Antibody Concentrations Against Toxins A and B Measured by Toxin Neutralization Assay (TNA)

Serum antibody concentrations against toxins A and B were measured by TNA and expressed as geometric mean titer (GMT). The 2-sided 95% Cl of GMT was based on the Student t-distribution.

Time frame:
Day 0, Day 14, Day 30, Day 60, Day 210, Day 390, Day 570, Day 750, Day 930, and Day 1110
Reported as:
Geometric mean · Titer (1/dilution)
Serum Antibody Concentrations Against Toxins A and B Measured by Toxin Neutralization Assay (TNA)
Titer (1/dilution)C. Difficile Vaccine GroupPlacebo Group
Toxin A TNA: Day 09.86 (9.22 to 10.5)10.1 (9.12 to 11.2)
Toxin A TNA: Day 1428.5 (22.7 to 35.8)9.86 (8.96 to 10.8)
Toxin A TNA: Day 3050.5 (40.9 to 62.3)9.97 (9.09 to 10.9)
Toxin A TNA: Day 60269 (226 to 322)9.82 (8.95 to 10.8)
Toxin A TNA: Day 210269 (228 to 317)10.3 (9.09 to 11.7)
Toxin A TNA: Day 390217 (183 to 259)10.1 (8.86 to 11.5)
Toxin A TNA: Day 570184 (153 to 223)9.86 (8.76 to 11.1)
Toxin A TNA: Day 750186 (148 to 234)10.2 (8.66 to 12.0)
Toxin A TNA: Day 930173 (125 to 240)10.7 (8.57 to 13.4)
Toxin A TNA: Day 1110212 (137 to 329)10.2 (8.03 to 12.9)
Toxin B TNA: Day 012.3 (11.2 to 13.6)13.2 (11.2 to 15.6)
Toxin B TNA: Day 1432.7 (25.3 to 42.2)13.3 (11.3 to 15.7)
Toxin B TNA: Day 3037.8 (29.3 to 48.8)13.4 (11.3 to 15.8)
Toxin B TNA: Day 6043.9 (34.0 to 56.6)14.3 (11.9 to 17.2)
Toxin B TNA: Day 21041.4 (32.4 to 53.1)13.2 (11.1 to 15.5)
Toxin B TNA: Day 39038.4 (30.0 to 49.0)13.5 (11.3 to 16.1)
Toxin B TNA: Day 57035.7 (27.7 to 46.0)13.7 (11.3 to 16.8)
Toxin B TNA: Day 75034.3 (25.1 to 46.9)14.6 (11.2 to 18.9)
Toxin B TNA: Day 93031.0 (21.1 to 45.6)17.0 (12.3 to 23.5)
Toxin B TNA: Day 111046.8 (26.1 to 84.1)14.0 (9.05 to 21.7)
SecondaryPercentage of Participants With >= 2 and 4-Fold Rise in Serum Antibody Concentrations From Baseline Against Toxins A and B Measured by TNA

Percentage of Participants with \>= 2 and 4-fold rise in serum antibody concentrations against toxins A and B were measured by TNA. The 2-sided 95% CI of the percentage was based on Exact method calculations.

Time frame:
Day 60
Reported as:
Number · percentage of participants
Percentage of Participants With >= 2 and 4-Fold Rise in Serum Antibody Concentrations From Baseline Against Toxins A and B Measured by TNA
percentage of participantsC. Difficile Vaccine GroupPlacebo Group
Toxin A TNA: >=285.6 (81.9 to 88.8)0.5 (0.0 to 2.5)
Toxin A TNA: >=478.2 (74.0 to 82.0)0.5 (0.0 to 2.5)
Toxin B TNA: >=230.9 (26.5 to 35.5)2.8 (1.0 to 5.9)
Toxin B TNA: >=427.4 (23.2 to 31.8)1.8 (0.5 to 4.7)
SecondarySerum Antibody Concentrations Against Toxins A and B Measured by TNA in Participants With CDI

Serum antibody concentrations against toxins A and B were measured by TNA and were expressed as GMT. The 2-sided 95% CI GMC was based on the Student t-distribution. Symptomatic PCR confirmed CDI cases were defined as the number of participants with combination of clinical and laboratory findings. Clinical components were: \>= 3 loose stools in \<= 24 hours, loose stools (defined as type 6 \[fluffy pieces with ragged edges, mushy\] or type 7 \[watery, no solid pieces\] according to the Bristol Stool Chart) lasting \>= 24 hours. Laboratory findings were: stool sample positive for C. difficile Toxin B by PCR at central laboratory or diagnosis of pseudomembranous colitis visualized at colonoscopy.

Time frame:
Day 0 and Day 60
Reported as:
Geometric mean · Titer (1/dilution)
Serum Antibody Concentrations Against Toxins A and B Measured by TNA in Participants With CDI
Titer (1/dilution)C. Difficile Vaccine GroupPlacebo Group
Toxin A TNA: Day 012.4 (8.59 to 17.9)12.0 (6.27 to 23.0)
Toxin A TNA: Day 60176 (83.4 to 371)10.7 (5.77 to 19.7)
Toxin B TNA: Day 016.7 (9.46 to 29.5)11.1 (7.57 to 16.3)
Toxin B TNA: Day 6053.0 (18.3 to 153)13.1 (8.11 to 21.0)
SecondaryPercentage of Participants Reporting Solicited Injection Site and Systemic Reactions

Solicited injection site reactions: pain, erythema, and swelling. Pain: Grade 1: no interference with activity, Grade 2: some interference with activity, Grade 3: significant; prevents daily activity; Erythema and swelling: Grade 1: \>= 25 to \<=50 mm, Grade 2: \>51 to \<=100 mm, Grade 3: \>100 mm. Solicited systemic reactions: fever, headache, malaise, myalgia, and arthralgia. Fever: Grade 1: \>= 38.0°C to \<=38.4°C or \>= 100.4° Fahrenheit (F) to \<=101.1°F, Grade 2: \>=38.5°C to \<= 38.9°C or \>=101.2°F to \<=102.0°F, Grade 3: \>=39.0°C or \>=102.1°F. Headache, malaise, and myalgia: Grade 1: no interference with activity, Grade 2: some interference with activity, Grade 3: significant; prevents daily activity; Arthralgia: Grade 1: free range of motion but complains of pain or discomfort, Grade 2: decreased range of motion due to pain or discomfort, Grade 3: unwilling to move due to pain.

Time frame:
Day 0 to Day 6 after any vaccination
Reported as:
Number · percentage of participants
Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions
percentage of participantsC. Difficile Vaccine GroupPlacebo Group
Injection site Pain38.613.5
Injection site Erythema4.20.0
Injection site Swelling3.80.3
Fever4.85.7
Headache25.322.5
Malaise23.919.6
Myalgia26.621.2
Arthralgia19.516.7

Adverse events

Collected over Adverse events data was collected throughout the study (up to 3 years).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
C. Difficile Vaccine Group255/6,113 (4.2%)1,662/6,113 (27.2%)1,347/6,113 (22%)
Placebo Group127/3,057 (4.2%)851/3,057 (27.8%)401/3,057 (13.1%)
Most frequent serious events
Showing 10 of 935
Most frequent serious events
EventC. Difficile Vaccine GroupPlacebo Group
PneumoniaInfections and infestations107/611367/3057
Chronic Obstructive Pulmonary DiseaseRespiratory, thoracic and mediastinal disorders84/611351/3057
Urinary Tract InfectionInfections and infestations91/611338/3057
CellulitisInfections and infestations63/611336/3057
Cardiac Failure CongestiveCardiac disorders69/611329/3057
Acute Myocardial InfarctionCardiac disorders56/611322/3057
Chest PainGeneral disorders50/611319/3057
OsteoarthritisMusculoskeletal and connective tissue disorders47/611319/3057
Atrial FibrillationCardiac disorders42/611314/3057
SepsisInfections and infestations34/611318/3057
Most frequent other events
Most frequent other events
EventC. Difficile Vaccine GroupPlacebo Group
Injection Site PainGeneral disorders855/6113127/3057
HeadacheNervous system disorders531/6113229/3057
MyalgiaMusculoskeletal and connective tissue disorders368/6113132/3057
ArthralgiaMusculoskeletal and connective tissue disorders345/6113146/3057
MalaiseGeneral disorders325/6113135/3057

Baseline characteristics

Analysis was performed on all randomized participants.

Age, Continuous
Age, Continuous(years)C. Difficile Vaccine GroupPlacebo GroupTotal
Mean65.9 ± 8.8665.8 ± 8.8765.8 ± 8.86
Sex: Female, Male
Sex: Female, Male(Participants)C. Difficile Vaccine GroupPlacebo GroupTotal
Female262912943923
Male357218075379
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)C. Difficile Vaccine GroupPlacebo GroupTotal
Hispanic or Latino330171501
Not Hispanic or Latino278013904170
Unknown or Not Reported309115404631
Race (NIH/OMB)
Race (NIH/OMB)(Participants)C. Difficile Vaccine GroupPlacebo GroupTotal
American Indian or Alaska Native6612
Asian7953981193
Native Hawaiian or Other Pacific Islander549
Black or African American206102308
White298314874470
More than one race8513
Unknown or Not Reported219810993297
08

Study locations

335 sites
  • Huntsville, Alabama 35803, United States
  • Investigational Site 104
    Mobile, Alabama 36608, United States
  • Flagstaff, Arizona 86001, United States
  • Investigational Site 194
    Phoenix, Arizona 85018, United States
  • Investigational Site 503
    Surprise, Arizona 85374, United States
  • Little Rock, Arkansas 72205, United States
  • Bakersfield, California 93301, United States
  • Banning, California 92220, United States
  • Garden Grove, California 92844, United States
  • La Mesa, California 91942, United States
  • Investigational Site 534
    Los Angeles, California 90022, United States
  • Investigational Site 051
    Los Angeles, California 90027, United States
  • Modesto, California 95350, United States
  • Redding, California 96001, United States
  • Sacramento, California 95817, United States
  • Investigational Site 504
    Simi Valley, California 93065, United States
  • Investigational Site 057
    Stanford, California 94305, United States
  • Investigational Site 176
    Upland, California 91786, United States
  • Ventura, California 93003, United States
  • Investigational Site 546
    Wheat Ridge, Colorado 90033, United States
  • Bristol, Connecticut 06010, United States
  • Danbury, Connecticut 06810, United States
  • Investigational Site 143
    Bradenton, Florida 34209, United States
  • Investigational Site 187
    Brandon, Florida 33511, United States
  • Investigational Site 075
    Clearwater, Florida 33756, United States
  • Investigational Site 517
    Clearwater, Florida 33765, United States
  • Investigational Site 055
    Crystal River, Florida 34429, United States
  • DeLand, Florida 32720, United States
  • Investigational Site 506
    Gainesville, Florida 32607, United States
  • Investigational Site 099
    Hialeah, Florida 33012, United States
  • Investigational Site 009
    Jacksonville, Florida 32216, United States
  • Lauderdale Lakes, Florida 33319, United States
  • Miami, Florida 33165, United States
  • Orange Park, Florida 32073, United States
  • Investigational Site 112
    Pensacola, Florida 32504, United States
  • Port Saint Lucie, Florida 34987, United States
  • Investigational Site 040
    Saint Petersburg, Florida 33709, United States
  • Investigational Site 114
    Saint Petersburg, Florida 33713, United States
  • Investigational Site 088
    Sarasota, Florida 34239, United States
  • Tamarac, Florida 33321, United States
  • Tampa, Florida 33612, United States
  • West Palm Beach, Florida 33401, United States
  • Investigational Site 149
    Augusta, Georgia 30912, United States
  • Investigational Site 529
    Decatur, Georgia 30030, United States
  • Macon, Georgia 31201, United States
  • Investigational Site 010
    Savannah, Georgia 31406, United States
  • Investigational Site 049
    Idaho Falls, Idaho 83494, United States
  • Investigational Site 543
    Pocatello, Idaho 83201, United States
  • Evanston, Illinois 60201, United States
  • Peoria, Illinois 61602, United States
  • Peoria, Illinois 61614, United States
  • Anderson, Indiana 46011, United States
  • Investigational Site 101
    Iowa City, Iowa 52242, United States
  • Topeka, Kansas 66606, United States
  • Louisville, Kentucky 40202, United States
  • Investigational Site 091
    Metairie, Louisiana 70006, United States
  • Investigational Site 084
    New Orleans, Louisiana 70121, United States
  • Opelousas, Louisiana 70570, United States
  • Investigational Site 077
    Shreveport, Louisiana 71101, United States
  • Auburn, Maine 04210, United States
  • Baltimore, Maryland 21224, United States
  • Investigational Site 002
    Boston, Massachusetts 02215, United States
  • Investigational Site 035
    West Roxbury, Massachusetts 02132, United States
  • Investigational Site 190
    Ann Arbor, Michigan 48106, United States
  • Investigational Site 175
    Detroit, Michigan 48202, United States
  • Investigational Site 183
    Flint, Michigan 48504, United States
  • Grosse Pointe Woods, Michigan 48236, United States
  • Kalamazoo, Michigan 49007, United States
  • Livonia, Michigan 48152, United States
  • Investigational Site 069
    Royal Oak, Michigan 48073, United States
  • Stevensville, Michigan 49127, United States
  • Troy, Michigan 48098, United States
  • Butte, Montana 59701, United States
  • Investigational Site 189
    Hillsborough, New Jersey 8844, United States
  • Investigational Site 044
    Neptune, New Jersey 07753, United States
  • Teaneck, New Jersey 07666, United States
  • Albuquerque, New Mexico 27103, United States
  • Albuquerque, New Mexico 87102, United States
  • Bronx, New York 10467, United States
  • Investigational Site 013
    Bronx, New York 10468, United States
  • Investigational Site 022
    Endwell, New York 13760, United States
  • Rochester, New York 14621, United States
  • Rochester, New York 14642, United States
  • Syracuse, New York 13210, United States
  • Investigational Site 146
    Asheville, North Carolina 28805, United States
  • Cary, North Carolina 27518, United States
  • Charlotte, North Carolina 28209, United States
  • Hickory, North Carolina 28602, United States
  • Raleigh, North Carolina 27612, United States
  • Raleigh, North Carolina 48202, United States
  • Statesville, North Carolina 28625, United States
  • Wilmington, North Carolina 28401, United States
  • Winston-Salem, North Carolina 27103, United States
  • Investigational Site 031
    Fargo, North Dakota 58104, United States
  • Fargo, North Dakota 58122, United States
  • Investigational Site 523
    Canton, Ohio 44710, United States
  • Cincinnati, Ohio 45219, United States
  • Cleveland, Ohio 44106, United States
  • Investigational Site 129
    Cleveland, Ohio 44109, United States
  • Cleveland, Ohio 44118, United States

Showing the first 100 of 335 sites across 26 countries.

09

References and documents

Publications

  • de Bruyn G, Gordon DL, Steiner T, Tambyah P, Cosgrove C, Martens M, Bassily E, Chan ES, Patel D, Chen J, Torre-Cisneros J, Fernando De Magalhaes Francesconi C, Gesser R, Jeanfreau R, Launay O, Laot T, Morfin-Otero R, Oviedo-Orta E, Park YS, Piazza FM, Rehm C, Rivas E, Self S, Gurunathan S. Safety, immunogenicity, and efficacy of a Clostridioides difficile toxoid vaccine candidate: a phase 3 multicentre, observer-blind, randomised, controlled trial. Lancet Infect Dis. 2021 Feb;21(2):252-262. doi: 10.1016/S1473-3099(20)30331-5. Epub 2020 Sep 15. PubMed 32946836 ↗

Study documents

  • Study protocol · Feb 14, 2017
  • Statistical analysis plan · Sep 5, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 28, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01887912
Lead sponsor
Sanofi Pasteur, a Sanofi Company
Responsible party
Sponsor
First posted
Jun 27, 2013
Start date
Jul 30, 2013
Primary completion
Jun 12, 2018
Completion
Jun 12, 2018
Results posted
Jul 5, 2019
Last update
Mar 28, 2022

Study contacts

Medical Director
study director · Sanofi Pasteur Inc.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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