A Randomized, Controlled Trial on the Efficacy and Safety of Live-Attenuated Influenza Vaccine (LAIV) Among Children in Bangladesh

Summary

This is a single center, multi-site, double-blind, parallel group, placebo-controlled trial of the clinical efficacy of trivalent Serum Institute of India, Ltd. (SIIL)live-attenuated influenza vaccine (LAIV) vaccine among children aged 24 through 59 months in Bangladesh. Background: 1. Burden: Within Bangladesh, community- based influenza surveillance identified 84.5 cases/1000 children-years among children \<5 years, while 10% of clinical pneumonia cases were influenza positive in this age group. 2. Knowledge gap: There has never been a randomized clinical efficacy trial of the SIIL LAIV vaccine conducted among children in a low-income country. 3. Relevance: Another LAIV vaccine (made by MedImmune) has been shown to have high efficacy against laboratory-confirmed influenza among children. The SIIL LAIV has the potential to be an inexpensive intervention to prevent pediatric influenza disease. Primary Hypothesis: In children aged 24 through 59 months in Bangladesh, LAIV is efficacious in reducing rates of symptomatic, laboratory-confirmed influenza (vaccine-matched strains) among children vaccinated with LAIV as compared to children vaccinated with a placebo through the first influenza season following vaccination. Primary Objective: To determine the efficacy of LAIV in reducing rates of symptomatic, laboratory-confirmed influenza virus infection (vaccine-matched strains) among children receiving LAIV as compared to children receiving a placebo through the first influenza season following vaccination (through December 2013). Methods: A total of 1761 children will be enrolled and randomized in a 2:1 ratio of LAIV to placebo beginning in March 2013. After vaccination, all children will be evaluated for reactions with one home visit four days post vaccination. Subsequently, all children will be monitored weekly for safety outcomes and illness signs at weekly field worker home visits through December 2013. An extended surveillance period was added to this study and, for participants consenting to additional follow-up, surveillance will extend through a second season (through September 2014). Participants with illness signs will be referred to the study clinic for evaluation using standardized diagnostic criteria and treatment by a study physician. Children meeting protocol-defined clinical Specimen Collection Criteria will have a nasopharyngeal wash specimen collected. Clinical specimens will be tested by Real time polymerase chain reaction (rRT-PCR) for evidence of influenza virus infection. Primary Outcome measures/variables: Vaccine efficacy will be assessed against symptomatic, laboratory-confirmed influenza for all circulating virus strains.

Timeline

Start

2013-02

Primary completion

2014-09

Completion

2014-09

Outcome

Met primary endpoint

registry NUMBER Vaccine: 6.7 percentage of participants NCT01797029 ↗

registry Vaccine vs Placebo; p <0.0001; Fisher Exact NCT01797029 ↗

paper Laboratory-confirmed influenza illness due to vaccine-matched strains was seen in 93 (15·8%) children in the placebo group and 79 (6·7%) in the LAIV group. PMID 27746226 ↗

Publications

• Rotrosen E, Zaman K, Feser J, Ortiz JR, Goswami D, Sharmeen AT, Rahman M, Lewis KDC, Rahman MZ, Barin B, Brooks WA, Neuzil KM. Influenza Among Young Children in Bangladesh: Clinical Characteristics and Outcomes From a Randomized Clinical Trial. Clin Infect Dis. 2017 Nov 13;65(11):1914-1920. doi: 10.1093/cid/cix674.
• Brooks WA, Zaman K, Lewis KD, Ortiz JR, Goswami D, Feser J, Sharmeen AT, Nahar K, Rahman M, Rahman MZ, Barin B, Yunus M, Fry AM, Bresee J, Azim T, Neuzil KM. Efficacy of a Russian-backbone live attenuated influenza vaccine among young children in Bangladesh: a randomised, double-blind, placebo-controlled trial. Lancet Glob Health. 2016 Dec;4(12):e946-e954. doi: 10.1016/S2214-109X(16)30200-5. Epub 2016 Oct 13.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	LAIV	Vaccine	—	Intranasal

Indications