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    The EU Clinical Trials Register currently displays   44339   clinical trials with a EudraCT protocol, of which   7369   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2008-004907-69
    Sponsor's Protocol Code Number:H-030-011
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2008-10-03
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2008-004907-69
    A.3Full title of the trial
    A Phase II randomized, placebo-controlled, double-blind, dose ranging study of a Clostridium difficile toxoid vaccine (ACAM-CDIFF) in subjects with Clostridium difficile-associated infection(CDI)
    A.3.2Name or abbreviated title of the trial where available
    N/A
    A.4.1Sponsor's protocol code numberH-030-011
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberN/A
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorSanofi Pasteur Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameACAM-CDIFF
    D.3.2Product code N/A
    D.3.4Pharmaceutical form Injection*
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntramuscular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNN/A
    D.3.9.1CAS number N/A
    D.3.9.2Current sponsor codeN/A
    D.3.9.3Other descriptive nameFormalin inactivated Clostridium difficile Toxoids A & B
    D.3.10 Strength
    D.3.10.1Concentration unit µg/ml microgram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.4
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboInjection*
    D.8.4Route of administration of the placeboIntramuscular use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Recurrence of Clostridium difficile Infection (CDI)
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 12.0
    E.1.2Level LLT
    E.1.2Classification code 10006834
    E.1.2Term C.difficile diarrhea
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 12.0
    E.1.2Level LLT
    E.1.2Classification code 10006835
    E.1.2Term C.difficile diarrhoea
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 12.0
    E.1.2Level LLT
    E.1.2Classification code 10012734
    E.1.2Term Diarrhea, Clostridium difficile
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 12.0
    E.1.2Level LLT
    E.1.2Classification code 10012748
    E.1.2Term Diarrhoea, Clostridium difficile
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 12.0
    E.1.2Level LLT
    E.1.2Classification code 10022661
    E.1.2Term Intestinal infection due to clostridium difficile
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 12.0
    E.1.2Level LLT
    E.1.2Classification code 10054236
    E.1.2Term Clostridium difficile infection
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare the event rate of CDI in groups assigned to ACAM-CDIFF vaccine (pooled groups) versus placebo in the 9 week period after the third dose of study vaccine (Study Days 29 to 91) in subjects with primary CDI up to 12 days prior to the first dose of study vaccine, receiving antibiotic standard of care.

    Primary CDI is defined as a documented, laboratory-confirmed CDI event that is either the first in the subject’s history or is occurring more than 90 days after a prior event.
    E.2.2Secondary objectives of the trial
    To evaluate safety of dose groups of vaccine (vax) vs placebo (pbo) in subs w/ primary CDI receiving antibiotic (AB) standard of care (SOC)
    To compare immunogenicity of dose groups of vax in subs with prim CDI receiving AB SOC
    To compare event rate of CDI in vax vs pbo groups starting at completion of AB treatment and ending at D91
    To compare event rate of CDI in vax vs pbo groups starting at completion of AB treatment and ending at the 3rd vax dose
    To compare event rate of CDI following admin of 100 µg dose of vax w/ adjuvant (adj) vs pbo starting at completion of AB treatment and ending at admin of the 3rd vax dose
    To compare event rate of CDI following admin of 100 µg dose of vax w/ adj vs pbo in the 9 weeks after the 3rd vax dose in subs w/ prim CDI receiving AB SOC
    To compare event rate of CDI in vax vs pbo groups in the long-term follow-up period
    To compare event rate of CDI following admin of 100 µg dose of vax w/ adj vs pbo in the long-term follow-up period
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Adult subjects aged ≥18 years.
    2. Subjects who have been diagnosed with primary CDI within the last 12 days. Primary CDI is defined as a documented, laboratory-confirmed CDI event that is either the first in the subject’s history or is occurring more than 90 days after a prior event.
    A CDI event is defined as follows:
    • a change in bowel habit with passage of 3 or more loose stools within a 24 hour period (that conforms to the shape of the container it is placed into)
    AND:
    • a positive result is obtained via stool toxin test for C. difficile using either ELISA/EIA or PCR. The ELISA/EIA assay can be used to test for both toxin A and toxin B, while PCR can be used to test only for toxin B and for toxin regulator genes.
    AND also:
    • absence of another identified cause for diarrhoea
    In addition, a stool cytotoxicity assay will be done in order to confirm the ELISA/EIA or PCR results. Vaccination may proceed before the results of this assay are known. However, if the results are available before a subject has received all 3 doses of ACAM-CDIFF vaccine and are found to be negative, vaccination will be halted, and the subject will be followed only for safety (until 6 months after the last vaccination).
    A positive result for the stool cytotoxicity assay means that the sample is either positive for cytotoxin or has a toxin-producing C. difficile by culture.
    3. Subjects who are judged by the investigator to be medically stable and have a White Cell Count (WCC) < 20,000 per µL and stable serum creatinine levels.
    4. Subjects who understand the risks and benefits of participation, are willing and able to comply with the study procedures and visit schedules outlined, and who have provided written informed consent for the study.
    5. All female subjects of child-bearing potential must not be pregnant or lactating, and must have a negative serum pregnancy test at screening. For females of child-bearing potential, one of the following methods of contraception must have been established at least 30 days prior to baseline examination and continue for 30 days post third vaccination:
    • Combined oral contraceptive pills (subjects should be consulted on the potential ineffectiveness of the oral contraceptive pill in the presence of diarrhoea and/or treatment with antibiotics, and barrier methods mandated as appropriate additional protection)
    • Combined contraceptive (as distinct from hormonal replacement) patch
    • Vaginal combined hormonal contraceptive ring
    • Injectable (combined and single) hormonal contraception (within effective time since injection)
    • Hormonal contraceptive (as distinct from hormonal replacement) implants
    • IUD (within appropriate time of insertion)
    6. Female subjects unable to bear children must have this documented in the case report form (e.g., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of 1 year since the last menstrual period]). Pregnancy testing of pre-menopausal women with tubal ligation without hysterectomy will be required at screening and during the study treatment period;
    7. Male subjects: If his partner might become pregnant the male subject’s partner must use a reliable form of contraception during the study, (one of the following methods of contraception must be used and continue for 30 days post third vaccination: e.g. oral contraception (for the partner) and condom, intra-uterine device (for the partner) and condom, or diaphragm with spermicide (for the partner) and a condom). Hormonal methods must have been established at least 30 days prior to baseline examination.
    E.4Principal exclusion criteria
    1. Subjects who are currently on treatment for a CDI recurrence, or who have had a documented, laboratory-confirmed CDI event, with or without treatment, within the past 90 days.
    2. Subjects who are currently or have recently (within one month prior to enrolment in trial) been treated with immunoglobulin therapy.
    3. Female subjects who are pregnant or breast feeding.
    4. Subjects with WCC > 20,000 per µL and acute rising serum creatinine levels (an acute increase of >50% increase as assessed by investigator).
    5. Concurrent, acutely life-threatening diseases.
    6. Predicted survival < 91 days as determined by the investigator
    7. Subjects with a platelet count of less than 70,000 cells/mm3 or other severe coagulation disorder that may increase risk of bleeding associated with vaccination.
    8. Subjects who are significantly immunocompromised or immunodeficient due to medications (current or expected during study course) or disease, including:
    • Subjects who are taking immunosuppressive therapy including systemic steroid therapy (e.g.; equivalent of prednisone ≥10 mg daily for more than 14 days) or who are expected to need to take such medication during the course of the study.
    • Subjects who are known to be HIV+
    9. Subjects who have received chemotherapy or radiation therapy within the past 6 months.
    10. Subjects with lymphoproliferative disorders.
    11. Subjects with a history of severe allergic reaction associated with respiratory distress, hypotension or other life-threatening condition to any medication or excipient including but not limited to alum and metronidazole or vancomycin.
    12. Subjects who are unable to receive antibiotic standard of care for CDI.
    13. Subjects with a body mass index (BMI) less than 14.0 kg/m2 or greater than 35 kg/ m2.
    14. Subjects who have chronic or persistent intermittent diarrhoea or abdominal pain due to active Crohn’s disease, Ulcerative Colitis, Celiac disease, or other non-C. difficile causes.
    15. Subjects who, in the opinion of the investigator, have any personal situation, medical condition, or illness (including mental illnesses) that could limit their ability to complete through Day 91 of the study including planned travel or surgery.
    16. Organ donation within 30 days of vaccination.
    17. Individuals who have previously received C. difficile toxoid vaccine.
    18. Receipt of any vaccine in the 30 days preceding the first trial vaccination, with the exception of influenza vaccine and pneumococcal vaccine
    19. Planned receipt of any vaccine in the 30 days following any trial vaccination, with the exception of influenza vaccine and pneumococcal vaccine
    20. Subjects who are receiving other non-standard of care therapy for CDI.
    21. Subjects who have any history of intestinal diverticular bleeding
    22. Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 30 days preceding the (first) trial vaccination.
    23. Planned participation in another clinical trial during the present trial period.
    24. Subjects who have had surgery within the past three months for GI malignancy.
    E.5 End points
    E.5.1Primary end point(s)
    Primary Endpoint: Efficacy. The event rate of CDI in groups assigned to ACAM-CDIFF (pooled groups) in the 9 week period after the third dose of study vaccine (Study Days 29 to 91) in subjects with primary CDI receiving antibiotic standard of care.

    Secondary Endpoint: Safety. A comparison of the frequency of local and systemic adverse events (AEs) and serious adverse events (SAEs), new laboratory abnormalities, reported in subjects assigned to ACAM-CDIFF vaccine (pooled) versus placebo will be performed. Clinical laboratory assessments and physical examinations will also be analyzed.

    Secondary Endpoint: Immunogenicity. The primary immunogenicity comparison will be seroconversion rates (% with increase in serum anti-toxin IgG titres compared to baseline) to C. difficile toxins A and B at day 42. The geometric mean titres (GMTs) will be also determined. Finally, the percentage of subjects that achieve ≥ 3 EU/mL anti-toxin A IgG levels at various time points will be determined.

    Secondary Endpoint: Efficacy. The event rate of CDI in specific study groups will be determined.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Immunogenicity
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Placebo-controlled, Dose Ranging
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned35
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    End of the trial is defined by the last patient completion of the Day 210 visit. Any related fatal event occurring during the study would trigger an immediate pause to further enrollment whilst the event is investigated by the IDMC and Sponsor. Such an event would always be unblinded by the IDMC. If the study is placed on hold, it would not restart until the Sponsor, IDMC, Medical Monitor and EC have agreed to a course of action, and the IRB has been notified and gives approval of this plan.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2008-10-03. Yes
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others Yes
    F.3.3.7.1Details of other specific vulnerable populations
    Elderly
    F.4 Planned number of subjects to be included
    F.4.1In the member state306
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 306
    F.4.2.2In the whole clinical trial 612
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    No arrangements are in place for continued provision of ACAM-CDIFF once the study is complete.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2008-11-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2008-11-21
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2011-07-11
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