IPV Clinical Trial - The Gambia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Medical Research Council Unit, The Gambia
ClinicalTrials.gov Identifier:
NCT01847872
First received: April 19, 2013
Last updated: September 8, 2014
Last verified: February 2014
  Purpose

The overall goal of this study is to identify interference between intramuscular Inactivated Polio Vaccine (IPV) and other vaccines (Measles Rubella and Yellow Fever) co-administered at nine months of age and to confirm the safety of co-administration. In addition, the study will compare the immunogenicity and safety of IPV when administered via different routes.

A total of 1504 healthy infants between the ages of nine to ten months, who have completed their primary immunizations, including at least three doses of trivalent Oral Polio Vaccine (tOPV) will be recruited for this study.


Condition Intervention Phase
Poliomyelitis
Drug: IPV IM Needle
Drug: IPV ID Needle
Drug: IPV IM Device
Drug: IPV ID Device
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase 4, Randomized Trial to Assess the Safety and Immunogenicity of Inactivated Poliovirus Vaccine When Given Concomitantly With Measles and Rubella Combined Vaccine and Yellow Fever Vaccine at Nine Months and When Administered Via Different Vaccination Routes

Resource links provided by NLM:


Further study details as provided by Medical Research Council Unit, The Gambia:

Primary Outcome Measures:
  • interference and immunugenicity [ Time Frame: 4 - 6 weeks after vaccination ] [ Designated as safety issue: No ]

    Serological responses (seropositivity for polioviruses 1, 2 and 3 and seroconversion for measles, rubella and yellow fever) will be measured four weeks following vaccination.

    Median antibody titers will be measured four weeks following vaccine administration


  • Safety [ Time Frame: up to 10 weeks after first vaccination ] [ Designated as safety issue: Yes ]
    Severe Adverse Event or Important Medical Event at any point during the study Any local AE (reactogenicity) on days 0, 1, 2 or 3 following vaccination using the IM or ID needle-free jet-injector devices or in the reference needle/syringe groups Any local or systemic Adverse Event on days 0 or 3 following all other vaccinations


Secondary Outcome Measures:
  • Cellular immune responses (B and T cells) to IPV vaccination [ Time Frame: up to 4 - 6 weeks post vaccination ] [ Designated as safety issue: No ]
    The poliovirus specific B-cell and T-cell responses following IPV vaccination using the IM or ID needle-free jet-injector or in the reference needle/syringe groups

  • stool tOPV quantification [ Time Frame: Day 14 - 21 after tOPV administration ] [ Designated as safety issue: No ]
    The level of poliovirus in the stool 14-21 days after a dose of tOPV in the context of previous IPV boosting using the IM or ID jet injector or in the reference needle/syringe routes.

  • time motion study [ Time Frame: 4- 6 weeks ] [ Designated as safety issue: No ]
    The time taken to administer IPV when the IM and ID needle/syringe routes are compared with the same routes of administration using a jet injector device

  • Perception of devices [ Time Frame: 4 to 6 weeks ] [ Designated as safety issue: No ]

    The perceptions of the vaccinators and parents/guardians regarding the needle-free jet-injector devices.

    For the parent/guardian a questionnaire with 4 questions will be administered following vaccination to assess parental/guardian perception of the device compared to standard needle and syringe base use.

    For the vaccinators will a questionnaire will be administered to assess their perception of the device in terms of ease of use and speed compared to standard needle and syringe base pair



Estimated Enrollment: 1504
Study Start Date: July 2013
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IPV IM (Visit 1)
IM IPV vaccine using syringe and needle pair is given at visit 1 followed by MR vaccine at visit 2 and YF vaccine at visit 3
Drug: IPV IM Needle
Other Name: Inactivated Poliovirus Vaccine Intramuscular using syringe and needle pair
Experimental: IPV IM (Visit 2)
MR vaccine at visit 1 followed by IM IPV vaccine using syringe and needle pair at visit 2, then YF vaccine at visit 3
Drug: IPV IM Needle
Other Name: Inactivated Poliovirus Vaccine Intramuscular using syringe and needle pair
Experimental: IPV IM (Device - Visit 2)
YF vaccine at visit 1 followed by IPV given IM using a Jet injector device at visit 2 and MR vaccine at visit 3
Drug: IPV IM Device
Other Name: Intramuscular Inactivated Poliovirus Vaccine using intramuscular Jet injector device
Experimental: IPV IM and MR (Visit1)
IM IPV using syringe and needle pair is given alongside MR at visit 1 followed by YF vaccine at visit 2
Drug: IPV IM Needle
Other Name: Inactivated Poliovirus Vaccine Intramuscular using syringe and needle pair
Experimental: IPV IM and YF (Visit 1)
IM IPV using syringe and needle pair is given alongside YF vaccine at visit 1 followed by MR at visit 2
Drug: IPV IM Needle
Other Name: Inactivated Poliovirus Vaccine Intramuscular using syringe and needle pair
Experimental: IPV ID (Visit 2)
MR and YF vaccines are co-administered at visit 1 followed by ID IPV using syringe and needle pair is given at visit 2
Drug: IPV ID Needle
Other Name: Inactivated Poliovirus Vaccine Intradermal using syringe and needle pair
Experimental: IPV IM and MR and YF (Visit 1)
IM IPV using syringe and needle pair is given alongside YF vaccine and MR vaccine at visit 1
Drug: IPV IM Needle
Other Name: Inactivated Poliovirus Vaccine Intramuscular using syringe and needle pair
Experimental: IPV (ID Device Visit 2)
MR vaccine is given at visit 1 followed by IPV vaccine by ID Jet injector device at visit 2 and YF vaccine at visit 3
Drug: IPV ID Device
Other Name: Intradermal Inactivated Poliovirus Vaccine using intradermal device

Detailed Description:

In studies conducted to date, Inactivated Polio Vaccine (IPV) appears to boost the systemic immunity generated by Oral Polio Vaccine (OPV) priming significantly more effectively than the use of additional doses of OPV. The use of IPV to both enhance the immunity generated by OPV and also to provide protection against circulating Vaccine Derived Polio Virus type 2 outbreaks and Vaccine Associated Paralytic Poliomyelitis has the potential to address concerns regarding a switch to bivalent OPV.

Concomitant administration with Expanded Program of Immunisations(EPI) vaccines given at about nine months would be a feasible programmatic approach. Maternal antibodies will have largely waned by this point negating any inhibitory effect which they may have within the priming schedule. Significant interference between IPV, Measles and Rubella (MR) and Yellow Fever (YF) vaccines must be excluded to ensure that IPV introduction does not negatively impact on the immunogenicity or safety of the other vaccines in the program at the same point.

Restricted manufacturing capacity in the context of a higher manufacturing cost than OPV would currently limit the rate at which IPV could be rolled out within a modified EPI schedule. The administration of a fractional dose of the vaccine by the Intradermal route would facilitate vaccine role out through limiting the cost and the manufacturing scale-up required. The proposed study is phase 4, eight-arm, open label, randomized controlled clinical vaccine trial. A total of 1504 randomized healthy infants between nine and ten months will receive IPV, MR and YF vaccines either alone, in combinations of two vaccines, or all three vaccines will be given together. Different routes (IM and fractional dose ID) and needle free jet injections devices for administration of IPV will be compared in the different groups. The participants will be assigned to one of eight groups using blocked randomization scheme in a 1:1:1:1:1:1:1:1:1 ratio.

Non- inferiority of serological responses and median antibody titers will be the primary immunogenicity end points. The incidence of serious adverse events and other important medical events at any point during the study will be the primary safety end point in all groups. Following device of reference needle/syringe administration, any local adverse event (reactogenicity), which will be collected on day 0(day of vaccination), day 1, day 2 and day 3 will be a second primary safety endpoint.

  Eligibility

Ages Eligible for Study:   9 Months to 10 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Nine to ten months of age inclusive
  • Receipt of at least three doses of tOPV (excluding a dose given at birth) a minimum of four weeks prior to recruitment date
  • Informed consent for trial participation obtained from a parent/guardian (see section 19.1.2 for definition of guardian and section 19.1.3 for details regarding consent procedure)
  • Resident in the study area and with no plans to travel outside the study area during the period of subject participation
  • Willingness and capacity to comply with the study protocol as judged by a member of the clinical trial team

Exclusion Criteria:

  • Use of any Investigational Medicinal Product(IMP) within the 28 days preceding enrolment
  • Planned administration of any vaccine outside those defined in the study protocol at anytime during trial participation (for procedure in the event of a national OPV campaign see section 12.5.1.1)
  • Previous receipt of a measles, rubella, yellow fever or IPV vaccine
  • Bacillus Calmette-Guérin(BCG) vaccination in the month prior to recruitment
  • Any suspected or confirmed congenital or acquired state of immune deficiency including but not limited to primary immunodeficiencies including thymus disorders, HIV/AIDS, hematological or lymphoid malignancies (blood tests will not be routinely undertaken with this regard as part of the study)
  • Any current immunosuppressive/immunomodulatory medication or treatment including, but not limited to corticosteroids, cyclosporin, azathioprine, cyclophosphamide, methotrexate, radiotherapy, bone marrow transplantation
  • Receipt of any immunosuppressive or immunomodulatory medication or treatment within the six months preceding trial enrolment (for corticosteroids this is defined as a dose of prednisolone (or equivalent) of greater than 2mg/kg/day for one week or 1mg/kg/day for one month. The use of inhaled or topical corticosteroids is not an exclusion criteria
  • Receipt of pooled human immunoglobulin, other blood product or any monoclonal antibody therapy at any point prior to recruitment or plans to receive such therapy at any point during the trial-
  • Any significant congenital defect or significant chronic health problem (e.g. chronic hematological (including severe anemia), renal, gastrointestinal, respiratory, neurological and cardiovascular disorders).
  • A history of anaphylactic or anaphylactoid reaction to egg, chicken proteins, neomycin, streptomycin polymyxin B, any previous vaccination or any individual component of one of the vaccines
  • Confirmed fructose intolerance
  • Severe protein-energy malnutrition (weight-for-age Z-score of less than -3)
  • Any clinically suspected or confirmed congenital or acquired clotting or bleeding disorder or any mediation known to significantly interfere with clotting (e.g. hemophilia or current anti-coagulant therapy) (blood tests will not be routinely undertaken with this regard as part of the study)
  • Any other condition which, in the opinion of the research clinician or ultimately the PI, is likely to interfere with the assessment of the primary and secondary objectives
  • Any significant signs or symptoms of an acute illness or infection including a tympanic temperature >38.0°C or documented fever >38°C in the preceding 48 hours
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01847872

Locations
Gambia
Medical Research Council Unit
Fajara, Gambia
Sponsors and Collaborators
Medical Research Council Unit, The Gambia
Investigators
Principal Investigator: Ed Clarke, MD Medical Research Council Unit, The Gambia
  More Information

No publications provided

Responsible Party: Medical Research Council Unit, The Gambia
ClinicalTrials.gov Identifier: NCT01847872     History of Changes
Other Study ID Numbers: SCC 1327
Study First Received: April 19, 2013
Last Updated: September 8, 2014
Health Authority: Gambia: Department of State for Health and Social Welfare

Keywords provided by Medical Research Council Unit, The Gambia:
Inactivated Poliovirus Vaccine
Randomised Control Phase IV Study
Gambia
IPV
Safety and Immunogenicity
Non-interference study
IM Jet injector
ID Jet Injector

Additional relevant MeSH terms:
Poliomyelitis
Central Nervous System Diseases
Central Nervous System Infections
Central Nervous System Viral Diseases
Enterovirus Infections
Myelitis
Nervous System Diseases
Neuromuscular Diseases
Picornaviridae Infections
RNA Virus Infections
Spinal Cord Diseases
Virus Diseases

ClinicalTrials.gov processed this record on October 20, 2014