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

Efficacy, Immunogenicity, and Safety Study of Clostridium Difficile Toxoid Vaccine in Subjects at Risk for C. Difficile Infection (Cdiffense™)

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.

Study Overview

• Status: Terminated
• Conditions: Clostridium Difficile Infection
• Intervention / Treatment: Biological: C. difficile Toxoid Vaccine; Biological: Placebo: 0.9% normal saline

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.

• Study Type: Interventional
• Enrollment (Actual): 9302
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
  • Queensland
    • Cairns, Queensland, Australia, 4870
      • Investigational Site 401
    • Woolloongabba, Queensland, Australia, 4102
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Investigational Site 404
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Investigational Site 403
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
    • Subiaco, Western Australia, Australia, 6008
• Brazil
  • Campinas, Brazil, 13020431
  • BA
    • Salvador, BA, Brazil, 40420-000
    • Salvador, BA, Brazil, 41253-190
  • GO
    • Aparecida de Goiânia, GO, Brazil, 74935-530
  • MG
    • Belo Horizonte, MG, Brazil, 30150-221
    • Belo Horizonte, MG, Brazil, 30190-130
    • Juiz De Fora, MG, Brazil, 36010-570
  • PE
    • Recife, PE, Brazil, 52020-010
  • PR
    • Curitiba, PR, Brazil, 80810-040
  • RJ
    • Nova Iguaçu, RJ, Brazil, 26030-380
    • Rio de Janeiro, RJ, Brazil, 22271-100
  • RN
    • Natal, RN, Brazil, 59025-600
  • RS
    • Canoas, RS, Brazil, 92425-900
    • Porto Alegre, RS, Brazil, 90035-003
  • SP
    • Santo Andre, SP, Brazil, 09060-650
• Canada
  • British Columbia
    • New Westminster, British Columbia, Canada, V3L 3W7
    • Surrey, British Columbia, Canada, V3V 1Z2
      • Investigational Site 156
    • Vancouver, British Columbia, Canada, V5Z IM9
      • Investigational Site 158
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A IR9
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
    • Truro, Nova Scotia, Canada, B2N 1L2
      • Investigational Site 163
  • Ontario
    • Guelph, Ontario, Canada, N1H 1B1
    • Toronto, Ontario, Canada, M5G 1X5
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
    • Pierrefonds, Quebec, Canada, H9H 4Y6
    • Québec, Quebec, Canada, G1E 7G9
      • Investigational Site 152
    • Sherbrooke, Quebec, Canada, J1H5N4
      • Investigational Site 151
    • Trois-Rivières, Quebec, Canada, G8Z 3R9
      • Investigational Site 161
• Colombia
  • Yopal, Colombia
  • Alantico
    • Barranquilla, Alantico, Colombia
  • Antioquia
    • Medellin, Antioquia, Colombia
  • Ditrito
    • Bogota, Ditrito, Colombia
  • Ditrito Capital
    • Bogota, Ditrito Capital, Colombia
  • Quindio
    • Armenia, Quindio, Colombia
  • Santander
    • Bucaramanga, Santander, Colombia
    • Floridablanca, Santander, Colombia
• Costa Rica
  • San José, Costa Rica, 250-1000
• Denmark
  • Aarhus, Denmark, 8200
    • Investigational Site 215
• Dominican Republic
  • Santo Domingo, Dominican Republic
    • Investigational Site 347
• Finland
  • Espoo, Finland, FIN-02100
  • Helsinki, Finland, FIN-00100
  • Helsinki, Finland, FIN-00930
  • Järvenpää, Finland, FIN-04400
    • Investigational Site 203
  • Kokkola, Finland, 67100
  • Oulu, Finland, FIN-90220
  • Pori, Finland, 28100
  • Seinajoki, Finland, 60100
  • Tampere, Finland, FIN-33100
    • Investigational Site 201
  • Turku, Finland, FIN-20520
    • Investigational Site 202
  • Vantaa, Finland, FIN-01300
• France
  • Dijon, France, 21079
    • Investigational Site 230
  • Lille, France, 49100
  • Limoges, France, 87042
  • Lyon, France, 69004
  • Montpellier, France, 34295
  • Orleans, France, 45100
  • Paris, France, 75014
    • Investigational Site 221
  • Pringy, France, 21079
    • Investigational Site 229
  • Saint Etienne, France, 42055
  • St Priest en Jarez, France, 42270
    • Investigational Site 223
  • Tourcoing, France, 59208
  • Tours, France, 37044
    • Investigational Site 232
• Germany
  • Berlin, Germany, 10629
  • Berlin, Germany, 13347
  • Essen, Germany, 45355
  • Goch, Germany, 47574
  • Hamburg, Germany, 20359
    • Investigational Site 247
  • Hamburg, Germany, 22143
    • Investigational Site 245
  • Leipzig, Germany, 97074
  • BW
    • Deggingen, BW, Germany, 73326
      • Investigational Site 244
  • Bavaria
    • Munich, Bavaria, Germany, 81675
  • Bayern
    • Wurzburg, Bayern, Germany, 97074
      • Investigational Site 242
  • NRW
    • Cologne, NRW, Germany, 50937
  • Sachsen
    • Leipzig, Sachsen, Germany, 04109
  • Thuringia
    • Jena, Thuringia, Germany, 07747
• Guatemala
  • Guatemala, Guatemala, 1001
• Japan
  • Aichi, Japan, 491-8551
    • Investigational Site 450
  • Chiba, Japan, 278-0004
    • Investigational Site 468
  • Fukui, Japan, 910-0067
    • Investigational Site 467
  • Fukuoka, Japan, 800-0344
    • Investigational Site 464
  • Fukuoka, Japan, 814-8525
    • Investigational Site 465
  • Fukuoka, Japan, 838-0069
    • Investigational Site 466
  • Gunma, Japan, 371-0014
    • Investigational Site 457
  • Hyōgo, Japan, 666-0125
    • Investigational Site 455
  • Ibaraki, Japan, 300-0028
    • Investigational Site 453
  • Kyoto, Japan, 611-0041
    • Investigational Site 460
  • Kyoto, Japan, 613-0034
    • Investigational Site 454
  • Nagano, Japan, 382-0091
    • Investigational Site 456
  • Nagano, Japan, 390-8601
    • Investigational Site 452
  • Nagano, Japan, 392-8510
    • Investigational Site 458
  • Okinawa, Japan, 904-2293
    • Investigational Site 469
  • Saitama, Japan, 348-0044
    • Investigational Site 459
  • Shimonoseki, Japan, 750-8520
    • Investigational Site 467
  • Tokyo, Japan, 171-0014
    • Investigational Site 451
  • Yamaguchi, Japan, 750-8520
    • Investigational Site 463
  • Ōsaka, Japan, 596-8522
    • Investigational Site 461
• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • Investigational Site 446
  • Cheongju, Korea, Republic of, 361-711
  • Gyeonggi-do, Korea, Republic of, 16247
    • Investigational Site 439
  • Gyeonggi-do, Korea, Republic of, 443-380
  • Incheon, Korea, Republic of, 21565
    • Investigational Site 412
  • Seoul, Korea, Republic of, 2841
    • Investigational Site 409
  • Seoul, Korea, Republic of, 3722
    • Investigational Site 408
  • Seoul, Korea, Republic of, 5355
    • Investigational Site 415
  • Seoul, Korea, Republic of, 5505
    • Investigational Site 418
  • Seoul, Korea, Republic of, 6351
    • Investigational Site 411
  • Seoul, Korea, Republic of, 7441
    • Investigational Site 437
  • Seoul, Korea, Republic of, 8308
    • Investigational Site 438
  • Gangnam-gu
    • Seoul, Gangnam-gu, Korea, Republic of, 135-710
  • Gangwon-do
    • Wŏnju, Gangwon-do, Korea, Republic of, 26427
      • Investigational Site 407
  • Gyeonggi-do
    • Ansan, Gyeonggi-do, Korea, Republic of, 15355
      • Investigational Site 413
  • Jung-Gu
    • Daegu, Jung-Gu, Korea, Republic of, 700-721
  • Namdong-gu
    • Incheon, Namdong-gu, Korea, Republic of, 22332
      • Investigational Site 427
  • Seocho-gu
    • Seoul, Seocho-gu, Korea, Republic of, 137-701
  • Seodaemun-gu
    • Seoul, Seodaemun-gu, Korea, Republic of, 120-752
  • Seongbuk-gu
    • Seoul, Seongbuk-gu, Korea, Republic of, 136-705
  • Seongdong-gu
    • Seoul, Seongdong-gu, Korea, Republic of, 132-792
  • Songpa-gu
    • Seoul, Songpa-gu, Korea, Republic of, 138-736
• Mexico
  • Durango, Mexico, 34000
    • Investigational Site 326
  • Morelos, Mexico
  • San Luis Potosi, Mexico, 78240
  • AGS
    • Aguascalientes, AGS, Mexico, 20230
  • Baja California
    • Tijuana, Baja California, Mexico, 22320
  • D.f.
    • Mexico City, D.f., Mexico, 14000
      • Investigational Site 325
    • Mexico City, D.f., Mexico, 14080
      • Investigational Site 329
  • Estado De Mexico
    • Ecatepec, Estado De Mexico, Mexico, 55076
      • Investigational Site 352
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Investigational Site 324
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62290
      • Investigational Site 351
  • NL
    • Monterrey, NL, Mexico, 64460
  • SLP
    • San Luis Potosi, SLP, Mexico, 78240
  • Tamaulipas
    • Ciudad Victoria, Tamaulipas, Mexico
      • Investigational Site 363
• Panama
  • Panama City, Panama
    • Investigational Site 354
• Peru
  • Lima, Peru
  • Lima, Peru, callao 2
    • Investigational Site 356
  • Lima, Peru, lima 1
    • Investigational Site 355
  • Piura, Peru, 200101
    • Investigational Site 365
  • La Libertad
    • Trujillo, La Libertad, Peru, 130101
      • Investigational Site 364
  • Lima
    • Jesus Maria, Lima, Peru, lima 11
      • Investigational Site 332
    • Lima Cercado, Lima, Peru
    • San Martín de Porres, Lima, Peru, lima 31
      • Investigational Site 334
    • Surquillo, Lima, Peru
• Philippines
  • Alabang, Philippines, 1770
  • Dasmarinas, Philippines, 4114
  • Manila, Philippines, 1000
  • Manila, Philippines, 1004
  • Pasig City, Philippines, 1600
  • Quezon City, Philippines, 1100
  • Quezon City, Philippines, 1101
• Poland
  • Bydgoszcz, Poland, 85-863
    • Investigational Site 284
  • Nowy Duninów, Poland, 09-505
    • Investigational Site 283
• Puerto Rico
  • Bayamon, Puerto Rico, 00960
    • Investigational Site 171
  • Bayamon, Puerto Rico, 00961
• Singapore
  • Singapore, Singapore, 169608
  • Singapore, Singapore, 119074
  • Singapore, Singapore, 119228
    • Investigational Site 419
  • Singapore, Singapore, 308433
    • Investigational Site 428
  • Singapore, Singapore, 768828
    • Investigational Site 445
• Spain
  • Cordoba, Spain, 14004
    • Investigational Site 294
  • Santander, Spain, 39008
    • Investigational Site 293
  • Terrassa, Spain, 08221
    • Investigational Site 292
  • Vigo, Spain, 36312
    • Investigational Site 295
• Sweden
  • Stockholm, Sweden, 11157
  • Umea, Sweden, 90185
  • SWE
    • Göthenburg, SWE, Sweden, 41685
• Taiwan
  • Kaohsiung, Taiwan, 813
  • New Taipei City, Taiwan, 22056
    • Investigational Site 426
  • New Taipei City, Taiwan, 23156
  • Taichung City, Taiwan, 40201
    • Investigational Site 429
  • Tainan, Taiwan, 71004
    • Investigational Site 421
  • Taipei, Taiwan, 10002
    • Investigational Site 425
  • Tiachung, Taiwan, 404
• Thailand
  • Bangkok, Thailand, 10330
    • Investigational Site 443
  • Bangkok, Thailand, 10400
    • Investigational Site 442
  • Khon Kaen, Thailand, 40002
    • Investigational Site 441
• United Kingdom
  • Blackpool, United Kingdom, FY3 7EN
    • Investigational Site 276
  • Blackpool, United Kingdom, FY3 8NR
  • Coventry, United Kingdom, CV2 2DX
    • Investigational Site 277
  • Harrow, United Kingdom, HA1 3UJ
  • Leeds, United Kingdom, LS9 7TF
    • Investigational Site 281
  • Liverpool, United Kingdom, L78XP
  • London, United Kingdom, SW17 0RE
    • Investigational Site 271
  • Manchester, United Kingdom, M8 5RB
  • Middlesex, United Kingdom, HA1 3UJ
  • North Shields, United Kingdom, NE29 8NH
  • Penzance, United Kingdom, TR19 7HX
    • Investigational Site 275
  • Stoke on Trent, United Kingdom, SR53SY
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35803
    • Mobile, Alabama, United States, 36608
      • Investigational Site 104
  • Arizona
    • Flagstaff, Arizona, United States, 86001
    • Phoenix, Arizona, United States, 85018
      • Investigational Site 194
    • Surprise, Arizona, United States, 85374
      • Investigational Site 503
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
  • California
    • Bakersfield, California, United States, 93301
    • Banning, California, United States, 92220
    • Garden Grove, California, United States, 92844
    • La Mesa, California, United States, 91942
    • Los Angeles, California, United States, 90022
      • Investigational Site 534
    • Los Angeles, California, United States, 90027
      • Investigational Site 051
    • Modesto, California, United States, 95350
    • Redding, California, United States, 96001
    • Sacramento, California, United States, 95817
    • Simi Valley, California, United States, 93065
      • Investigational Site 504
    • Stanford, California, United States, 94305
      • Investigational Site 057
    • Upland, California, United States, 91786
      • Investigational Site 176
    • Ventura, California, United States, 93003
  • Colorado
    • Wheat Ridge, Colorado, United States, 90033
      • Investigational Site 546
  • Connecticut
    • Bristol, Connecticut, United States, 06010
    • Danbury, Connecticut, United States, 06810
  • Florida
    • Bradenton, Florida, United States, 34209
      • Investigational Site 143
    • Brandon, Florida, United States, 33511
      • Investigational Site 187
    • Clearwater, Florida, United States, 33756
      • Investigational Site 075
    • Clearwater, Florida, United States, 33765
      • Investigational Site 517
    • Crystal River, Florida, United States, 34429
      • Investigational Site 055
    • DeLand, Florida, United States, 32720
    • Gainesville, Florida, United States, 32607
      • Investigational Site 506
    • Hialeah, Florida, United States, 33012
      • Investigational Site 099
    • Jacksonville, Florida, United States, 32216
      • Investigational Site 009
    • Lauderdale Lakes, Florida, United States, 33319
    • Miami, Florida, United States, 33165
    • Orange Park, Florida, United States, 32073
    • Pensacola, Florida, United States, 32504
      • Investigational Site 112
    • Port Saint Lucie, Florida, United States, 34987
    • Saint Petersburg, Florida, United States, 33709
      • Investigational Site 040
    • Saint Petersburg, Florida, United States, 33713
      • Investigational Site 114
    • Sarasota, Florida, United States, 34239
      • Investigational Site 088
    • Tamarac, Florida, United States, 33321
    • Tampa, Florida, United States, 33612
    • West Palm Beach, Florida, United States, 33401
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Investigational Site 149
    • Decatur, Georgia, United States, 30030
      • Investigational Site 529
    • Macon, Georgia, United States, 31201
    • Savannah, Georgia, United States, 31406
      • Investigational Site 010
  • Idaho
    • Idaho Falls, Idaho, United States, 83494
      • Investigational Site 049
    • Pocatello, Idaho, United States, 83201
      • Investigational Site 543
  • Illinois
    • Evanston, Illinois, United States, 60201
    • Peoria, Illinois, United States, 61602
    • Peoria, Illinois, United States, 61614
  • Indiana
    • Anderson, Indiana, United States, 46011
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Investigational Site 101
  • Kansas
    • Topeka, Kansas, United States, 66606
  • Kentucky
    • Louisville, Kentucky, United States, 40202
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Investigational Site 091
    • New Orleans, Louisiana, United States, 70121
      • Investigational Site 084
    • Opelousas, Louisiana, United States, 70570
    • Shreveport, Louisiana, United States, 71101
      • Investigational Site 077
  • Maine
    • Auburn, Maine, United States, 04210
  • Maryland
    • Baltimore, Maryland, United States, 21224
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Investigational Site 002
    • West Roxbury, Massachusetts, United States, 02132
      • Investigational Site 035
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Investigational Site 190
    • Detroit, Michigan, United States, 48202
      • Investigational Site 175
    • Flint, Michigan, United States, 48504
      • Investigational Site 183
    • Grosse Pointe Woods, Michigan, United States, 48236
    • Kalamazoo, Michigan, United States, 49007
    • Livonia, Michigan, United States, 48152
    • Royal Oak, Michigan, United States, 48073
      • Investigational Site 069
    • Stevensville, Michigan, United States, 49127
    • Troy, Michigan, United States, 48098
  • Montana
    • Butte, Montana, United States, 59701
  • New Jersey
    • Hillsborough, New Jersey, United States, 8844
      • Investigational Site 189
    • Neptune, New Jersey, United States, 07753
      • Investigational Site 044
    • Teaneck, New Jersey, United States, 07666
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
    • Albuquerque, New Mexico, United States, 27103
  • New York
    • Bronx, New York, United States, 10467
    • Bronx, New York, United States, 10468
      • Investigational Site 013
    • Endwell, New York, United States, 13760
      • Investigational Site 022
    • Rochester, New York, United States, 14621
    • Rochester, New York, United States, 14642
    • Syracuse, New York, United States, 13210
  • North Carolina
    • Asheville, North Carolina, United States, 28805
      • Investigational Site 146
    • Cary, North Carolina, United States, 27518
    • Charlotte, North Carolina, United States, 28209
    • Hickory, North Carolina, United States, 28602
    • Raleigh, North Carolina, United States, 27612
    • Raleigh, North Carolina, United States, 48202
    • Statesville, North Carolina, United States, 28625
    • Wilmington, North Carolina, United States, 28401
    • Winston-Salem, North Carolina, United States, 27103
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Investigational Site 031
    • Fargo, North Dakota, United States, 58122
  • Ohio
    • Canton, Ohio, United States, 44710
      • Investigational Site 523
    • Cincinnati, Ohio, United States, 45219
    • Cleveland, Ohio, United States, 44106
    • Cleveland, Ohio, United States, 44109
      • Investigational Site 129
    • Cleveland, Ohio, United States, 44118
    • Columbus, Ohio, United States, 43215
      • Investigational Site 003
    • Dayton, Ohio, United States, 45419
      • Investigational Site 061
    • Dayton, Ohio, United States, 45428
    • Kettering, Ohio, United States, 45429
    • Marion, Ohio, United States, 43302
    • Middletown, Ohio, United States, 45005
      • Investigational Site 095
  • Oregon
    • Bend, Oregon, United States, 97701
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • Investigational Site 528
    • Hershey, Pennsylvania, United States, 17033
    • Philadelphia, Pennsylvania, United States, 19140
    • Pittsburgh, Pennsylvania, United States, 15212
    • Pittsburgh, Pennsylvania, United States, 15240
    • Uniontown, Pennsylvania, United States, 15401
      • Investigational Site 083
    • West Reading, Pennsylvania, United States, 19611
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Investigational Site 020
  • Rhode Island
    • Pawtucket, Rhode Island, United States, 02860
      • Investigational Site 050
    • Providence, Rhode Island, United States, 02906
    • Providence, Rhode Island, United States, 02908
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Investigational Site 540
    • Mount Pleasant, South Carolina, United States, 29464
      • Investigational Site 047
    • Spartanburg, South Carolina, United States, 29303
      • Investigational Site 180
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Investigational Site 086
  • Tennessee
    • Franklin, Tennessee, United States, 37067
    • Jackson, Tennessee, United States, 38305
    • Nashville, Tennessee, United States, 37203
    • Nashville, Tennessee, United States, 37082
  • Texas
    • Austin, Texas, United States, 78726
      • Investigational Site 544
    • Corpus Christi, Texas, United States, 78413
    • Dallas, Texas, United States, 75216
      • Investigational Site 006
    • Fort Worth, Texas, United States, 76104
      • Investigational Site 119
    • Groesbeck, Texas, United States, 76642
    • San Antonio, Texas, United States, 78229
      • Investigational Site 193
    • Tomball, Texas, United States, 77375
  • Utah
    • Orem, Utah, United States, 84058
      • Investigational Site 135
    • Salt Lake City, Utah, United States, 84124
      • Investigational Site 080
  • Virginia
    • Lynchburg, Virginia, United States, 24501
      • Investigational site 012
    • Williamsburg, Virginia, United States, 23185
    • Winchester, Virginia, United States, 22601
      • Investigational Site 196
  • Washington
    • Spokane, Washington, United States, 99202
    • Tacoma, Washington, United States, 98405
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • Investigational Site 030
    • Weston, Wisconsin, United States, 54476

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; 0.5 mL, Intramuscular
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; 0.5 mL, Intramuscular

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 3 years post injection 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 3 years post injection 1
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.	Up to 3 years post injection 1
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).	Up to 3 years post injection 1
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).	Day 0, Day 14, Day 30, Day 60, Day 210, Day 390, Day 570, Day 750, Day 930, and Day 1110
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.	Day 60
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.	Day 0 and Day 60
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.	Day 0, Day 14, Day 30, Day 60, Day 210, Day 390, Day 570, Day 750, Day 930, and Day 1110
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.	Day 60
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.	Day 0 and Day 60
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.	Day 0 to Day 6 after any vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2013
• Primary Completion (Actual): June 12, 2018
• Study Completion (Actual): June 12, 2018

Study Registration Dates

• First Submitted: June 20, 2013
• First Submitted That Met QC Criteria: June 24, 2013
• First Posted (Estimate): June 27, 2013

Study Record Updates

• Last Update Posted (Actual): March 28, 2022
• Last Update Submitted That Met QC Criteria: March 21, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Clostridium difficile Toxoid Vaccine; Clostridium difficile infection; Cdiffense
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Clostridium Infections
• Other Study ID Numbers: H-030-014; 2013-000775-32 (EudraCT Number); U1111-1127-7162 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No