Pakistan Short Interval mOPV1 Compared With Standard Interval mOPV1 and bOPV 1,3

NCT ID: NCT01586572

Last Updated: 2015-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2013-05-31

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).

Conditions

Polio

Study Design

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

Study Groups

mOPV1- Arm A

Arm A will be administered a second dose of mOPV1 seven days after the 42 day mOPV1 index dose.Second dose of tOPV2 will be given at day 79.

Group Type: EXPERIMENTAL

mOPV1

Intervention Type: DRUG

Monovalent type 1 oral poliovirus vaccine (mOPV1) containing at least106 TCID50 of Sabin- strain poliovirus type 1.

mOPV1- Arm B

Arm B will be administered a second dose of mOPV1 fourteen days after after the 42 day mOPV1 index dose.Second dose of tOPV2 will be given at 86 days.

Group Type: EXPERIMENTAL

mOPV1

Intervention Type: DRUG

Monovalent type 1 oral poliovirus vaccine (mOPV1) containing at least106 TCID50 of Sabin- strain poliovirus type 1.

mOPV1-Arm C

Arm C will receive the second dose of mOPV1 thirty days after the 42 day mOPV1 index dose.Second dose of tOPV2 will be given at 102 days.

Group Type: EXPERIMENTAL

mOPV1

Intervention Type: DRUG

Monovalent type 1 oral poliovirus vaccine (mOPV1) containing at least106 TCID50 of Sabin- strain poliovirus type 1.

Arm D- bOPV1,3

Arm D will be administered a second dose of bOPV1,3 thirty days after the 42 day bOPV1,3 index dose.Second dose of tOPV2 will be given at day 102.

Group Type: EXPERIMENTAL

bOPV 1,3

Intervention Type: DRUG

The bivalent vaccine containing at least 106 CCID50 of Sabin poliovirus type 1 and 105•8 CCID50 of Sabin poliovirus type 3.

Interventions

mOPV1

Monovalent type 1 oral poliovirus vaccine (mOPV1) containing at least106 TCID50 of Sabin- strain poliovirus type 1.

Intervention Type: DRUG

bOPV 1,3

The bivalent vaccine containing at least 106 CCID50 of Sabin poliovirus type 1 and 105•8 CCID50 of Sabin poliovirus type 3.

Intervention Type: DRUG

Other Intervention Names

Monovalent type 1 oral poliovirus vaccine; Bivalent Oral Polio Vaccine

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.

• Minimum Eligible Age: 1 Hour
• Maximum Eligible Age: 24 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

World Health Organization

OTHER

Sponsor Role: collaborator

Aga Khan University

OTHER

Sponsor Role: lead

Responsible Party

Anita Kaniz Mehdi Zaidi

Professor and Chairperson, Pediatrics and Child Health

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anita KM Zaidi, MD; MSc

Role: PRINCIPAL_INVESTIGATOR

Aga Khan University

Fatima FM Mir, MBBS

Role: STUDY_DIRECTOR

Aga Khan University

Locations

Aga Khan University

Karachi, Sindh, Pakistan

Aga Khan University

Karachi, Sindh, Pakistan

Countries

Pakistan

References

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.

Reference Type: DERIVED

PMID: 26093979 (View on PubMed)

Other Identifiers

1891-Ped-ERC-11

Identifier Type: -

Identifier Source: org_study_id