IPV Clinical Trial - The Gambia

NCT ID: NCT01847872

Last Updated: 2018-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 1504 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2015-07-31

Brief Summary

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.

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.

Conditions

Poliomyelitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

IPV IM Needle

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

IPV IM Needle

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

IPV IM Device

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

IPV IM Needle

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

IPV IM Needle

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

IPV ID Needle

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

IPV IM Needle

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

IPV ID Device

Intervention Type: DRUG

Interventions

IPV IM Needle

Intervention Type: DRUG

IPV ID Needle

Intervention Type: DRUG

IPV IM Device

Intervention Type: DRUG

IPV ID Device

Intervention Type: DRUG

Other Intervention Names

Inactivated Poliovirus Vaccine Intramuscular using syringe and needle pair; Inactivated Poliovirus Vaccine Intradermal using syringe and needle pair; Intramuscular Inactivated Poliovirus Vaccine using intramuscular Jet injector device; Intradermal Inactivated Poliovirus Vaccine using intradermal device

Eligibility 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 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

• Minimum Eligible Age: 9 Months
• Maximum Eligible Age: 10 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ed Clarke, MD

Role: PRINCIPAL_INVESTIGATOR

Medical Research Council Unit, The Gambia

Locations

Medical Research Council Unit

Fajara, , The Gambia

Countries

The Gambia

References

Bibby J, Saidu Y, Umesi A, Moneke-Anyanwoke N, Bashorun AO, Hydara MB, Adigweme I, Adetifa JU, Okoye M, Roberts E, Clemens R, Bandyopadhyay AS, Muhammad AK, Mulwa S, Royals M, Jarrahian C, Jeffries D, Kampmann B, Clarke E. The Immunogenicity of Fractional Intradermal Doses of the Inactivated Poliovirus Vaccine Is Associated With the Size of the Intradermal Fluid Bleb. Clin Infect Dis. 2017 Sep 1;65(5):851-854. doi: 10.1093/cid/cix381.

Reference Type: DERIVED

PMID: 28444156 (View on PubMed)

Clarke E, Saidu Y, Adetifa JU, Adigweme I, Hydara MB, Bashorun AO, Moneke-Anyanwoke N, Umesi A, Roberts E, Cham PM, Okoye ME, Brown KE, Niedrig M, Chowdhury PR, Clemens R, Bandyopadhyay AS, Mueller J, Jeffries DJ, Kampmann B. Safety and immunogenicity of inactivated poliovirus vaccine when given with measles-rubella combined vaccine and yellow fever vaccine and when given via different administration routes: a phase 4, randomised, non-inferiority trial in The Gambia. Lancet Glob Health. 2016 Aug;4(8):e534-47. doi: 10.1016/S2214-109X(16)30075-4. Epub 2016 Jun 27.

Reference Type: DERIVED

PMID: 27364568 (View on PubMed)

Other Identifiers

SCC 1327

Identifier Type: -

Identifier Source: org_study_id