Clinical trial NCT01586572: Pakistan Short Interval mOPV1 Compared With Standard Interval mOPV1 and bOPV 1,3
Official title: Comparison of Immunogenicity of Type 1 mOPV Administered at Short Intervals With Type 1 mOPV1 and Type 1 & 3 bOPV Oral Polio Vaccine Given at Standard Intervals in Pakistan:A Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Polio
Keywords: Polio virus type 1,2,3
Poliovaccine-Oral
Poliovaccine
Trivalent Oral Polio vaccine
Monovalent oral polio vaccine
Bivalent Oral polio vaccine
Lead sponsor: Aga Khan University
Sponsor class: OTHER
Collaborators: name: World Health Organization
First posted: 2012-04-27
Enrollment: 1000
Sex: ALL
Minimum age (years): 1
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Globally, polio cases have decreased by over 99% since 1988. However, wild poliovirus cases continue in Pakistan. Conflict and lack of access to children due to on-going insecurity in tribal areas present special challenges in interrupting transmission rapidly. There exists limited knowledge on the effect of shorter intervals of mOPV vaccination on immunogenicity levels in young children. The aim of this study is to demonstrate the non-inferiority of shorter intervals (7 and 14 days) between doses of mOPV1 vaccine compared to the customary interval (30 days). A 4th arm will receive bivalent (bOPV) vaccine at standard intervals beginning at 6 weeks of age.

Detailed description: This randomized clinical trial which will be conducted in 5 low-income areas in and around Karachi (4 peri-urban, contiguous coastal villages outside Karachi, and one urban squatter settlement) where the Aga Khan University's Department of Paediatrics and Child Health has well-established demographic surveillance with all pregnancies and new births in the area captured through the system. The study participants will be enrolled from birth until 102 days. Subjects will be randomized to one of four trial arms.

All children will receive tOPV at birth. At 42 days (6 weeks) of age, three study arms will receive a dose of mOPV1 whereas the fourth arm will receive a dose of bOPV1\&3 as per protocol. Then 7 or 14 or 30 days later, the study participants in Arms A, B, and C will receive a second dose of mOPV1 while a second dose of bOPV 1\&3 will be given to participants in Arm D at 30 days.

Name and description of products:

1. Standard trivalent oral poliovirus vaccine (tOPV), in a 10:1:6 formulation, containing at least 106 TCID50 of Sabin -strain poliovirus type 1, at least 105 TCID50 of Sabin-strain poliovirus type 2 and at least 105.8 TCID50 of Sabin-strain poliovirus type 3.
2. Monovalent type 1 oral poliovirus vaccine (mOPV1) containing at least106 TCID50 of Sabin- strain poliovirus type 1.
3. The bivalent oral polio vaccine containing at least 106 CCID50 of Sabin poliovirus type 1 and 105•8 CCID50 of Sabin poliovirus type 3.

Sample Size:

To show non-inferiority of a 2-dose mOPV1 schedule with shorter-intervals (either 7 or 14 days) \[intervention\] compared to a 2-dose mOPV1 schedule administered at 30-day intervals \[control\], and a 2-dose bOPV13 schedule administered at a 30-day interval (control) assuming a power of 0.90 (beta) and p of 0.05 (alpha), we require a sample of 139 for each study group, for a total of 556 subjects. To compensate for drop out, attrition and insufficient sera for laboratory testing, an inflated (by \~ 50%) sample size of 200 in each group will be used (total sample size of 800)

Efficacy Endpoints:

The primary endpoint is seroconversion with antibodies to poliovirus type 1 following a two-dose schedule of mOPV1 given at intervals of 7 and 14 days compared to mOPV1 and bOPV1\&3 given at the standard interval of 30 days..

The secondary endpoint is seroconversion following the birth dose of tOPV.

All samples will be processed at the Centers of Disease Control and Prevention CDC) Laboratories (a Global Specialized Polio Network Laboratory).

Eligibility criteria: Inclusion Criteria:

* Infants \> 2.5 kg birth weight
* Immediate cry
* No neonatal IMCI danger signs
* Not planning to travel away during entire the study period (birth-102 days)

Exclusion Criteria:

* High-risk newborns will be excluded, as well as newborns requiring hospitalization
* Birth weight below 2.5 kg
* Cry \>2 minutes
* With any neonatal IMNCI danger signs
* Residence \>30 km from study site
* Family is planning to be absent during the birth - 102 day study period.
* A diagnosis or suspicion of immunodeficiency disorder (either in the participant or in a member of the immediate family - e.g. several early infant deaths, household member on chemotherapy) will render the newborn ineligible for the study.

Primary outcomes:
measure: Seroconversion with antibodies to poliovirus type 1 following a two-dose schedule of mOPV1 given at intervals of 7 and 14 days compared to mOPV1 and bOPV1&3 given at the standard interval of 30 days.
timeFrame: Participants will be followed till 102 days after birth
Secondary outcomes:
measure: Seroconversion following the birth dose of tOPV.
timeFrame: At birth
Other outcomes:
Locations:
city: Karachi
country: Pakistan
facility: Aga Khan University
state: Sindh
city: Karachi
country: Pakistan
facility: Aga Khan University
state: Sind
Study officials:
affiliation: Aga Khan University
name: Anita KM Zaidi, MD; MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Aga Khan University
name: Fatima FM Mir, MBBS
role: STUDY_DIRECTOR
References:
citation: Mir F, Quadri F, Mach O, Ahmed I, Bhatti Z, Khan A, Rehman NU, Durry E, Salama M, Oberste SM, Weldon WC, Sutter RW, Zaidi AK. Monovalent type-1 oral poliovirus vaccine given at short intervals in Pakistan: a randomised controlled, four-arm, open-label, non-inferiority trial. Lancet Infect Dis. 2015 Aug;15(8):889-97. doi: 10.1016/S1473-3099(15)00093-6. Epub 2015 Jun 17.