Phase III Clinical Trial to Assess the Immunogenicity of a Sequential Dose of Fractional Inactivated Polio Vaccine (f-IPV) and Oral Polio Vaccine (OPV)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,206
- 试验地点
- 1
- 主要终点
- Seroconversion
研究概览
简要总结
This study is an open-label phase III randomized clinical trial that would compare immunogenicity after receiving one of five different combinations of polio vaccines. Infants will be enrolled and randomized at 6 weeks of age to one of five different arms:
A) Three doses of trivalent oral poliovirus vaccine (tOPV) at 6, 10 and 14 weeks of age B) Three doses of bivalent OPV (bOPV) at 6, 10 and 14 weeks of age C) Two doses of intramuscular (IM) inactivated poliovirus vaccine (IPV) at 6 and 14 weeks of age D) Two doses of intra-dermal (ID) fractional IPV (f-IPV) at 6 and 14 weeks of age E) Sequential administration of ID f-IPV at 6 and 14 weeks of age with bOPV at 10 weeks of age To assess the immunogenicity of each study vaccine and vaccination schedule, antibody titers against poliovirus types 1, 2 and 3 will be determined in sera extracted from blood collected before (at 6 weeks of age) and after receiving 3 doses of study vaccine (18 weeks of age). Seroconversion will be defined as a titer 4-fold higher than the expected fall in maternally derived antibodies, assuming a half-life of 28 days. The initial antibody titer at 6 weeks of age will be used as the starting point for the expected decline in maternal antibody.
This study will compare the immunogenicity of:
- Sequential dose of intra-dermal f-IPV and bOPV to bOPV alone administered at 6, 10 and 14 weeks of age
- tOPV to bOPV administered at 6,10 and 14 weeks of age
- IM IPV to ID f-IPV administered at 6 and 14 weeks of age The answer to these questions will guide the global polio eradication program in designing new routine immunization schedule for children that eliminates the risks of paralysis due to vaccine derived poliovirus (VDPV) from type 2 vaccine poliovirus.
详细描述
Global polio eradication initiative (GPEI)
In 1988, the World Health Assembly adopted the resolution of polio eradication by 2000. This launched the Global Polio Eradication Initiative (GPEI), spearheaded by World Health Organization (WHO), Rotary International, US Centers for Disease Control and Prevention (CDC) and United Nations Children's Emergency Fund (UNICEF). The major strategies to achieve polio eradication included: 1) provision of 3-4 doses of tOPV to young infants through routine immunization programs; 2) provision of additional doses to all children < 5 years of age through immunization campaigns (supplementary immunization activities or SIAs); 3) surveillance for all cases of acute flaccid paralysis in children <15 years of age; and 4) mop-up immunizations campaigns following the detection of poliovirus circulation.
OPV was the vaccine of choice for polio eradication due to its low cost, ease of administration, ability to induce intestinal immunity and community spread to aid in induction of immunity.
Limitations of trivalent oral polio vaccine (tOPV)
tOPV is a mixture of all three types of polioviruses and there is interference among the strains during intestinal replication. Type 2 especially interferes with uptake of types 1 and 3. tOPV has higher seroconversion rates in industrialized countries compared to that in developing countries. A study conducted in Brazil and Gambia reported tOPV seroconversion rates of 85% for Type 1, 94% for type 2 and 68% for Type 3 with three doses of tOPV. Compared to monovalent OPVs, trivalent OPV has lower seroconversion rates. To address concerns of lower efficacy of tOPV for type 1 and type 3 compared to monovalent vaccines, monovalent vaccines were re-introduced in the polio eradication initiative. Monovalent OPVs are more immunogenic than tOPV. In India, compared to two doses of tOPV given at birth and after 30 days, type-specific seroconversion was significantly higher with two doses of mOPV1 (90% vs. 63%) and mOPV3 (84% vs. 52%). In South Africa, compared to one dose of tOPV given at birth, type-specific seroconversion was significantly higher with one dose of mOPV1 (73% vs. 39%) and mOPV3 (58% vs. 21%).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 6 Weeks 至 7 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy infants 6-7 weeks of age
- •Family that consents for participation in the full length of the study
- •Family that is able to understand and comply with planned study procedures
排除标准
- •Family that is unable to participate in the full length of the study
- •A diagnosis or suspicion of immunodeficiency disorder either in the infant or in an immediate family member
- •A diagnosis or suspicion of bleeding disorder that would contraindicate parenteral administration of IPV or collection of blood by venipuncture
- •Acute diarrhea, infection or illness at the time of enrollment (6-7 weeks of age) that would require infant's admission to a hospital or would contraindicate provision of OPV per country guidelines
- •Acute vomiting and intolerance to liquids within 24 hours before the enrollment visit (6 weeks of age)
- •Receipt of any polio vaccine (OPV or IPV) before enrollment based upon documentation or parental recall
- •Known allergy/sensitivity or reaction to polio vaccine or contents of polio vaccine
- •Infants from multiple births. Infants from multiple are excluded to reduce the potential for contact transmission of vaccine poliovirus. The infant from a multiple birth who is not enrolled is likely to receive routine immunization and transmit vaccine poliovirus to the enrolled infant
- •Infants from premature births (<37 weeks of gestation)
结局指标
主要结局
Seroconversion
时间窗: Change in antibody titers at 18 weeks of age compared to 6 weeks of age
The primary analytical approach will be intention-to-treat analysis on enrolled participants who have serological results available on blood specimens collected at 18 weeks of age. Reciprocal antibody titers of at least 1:8, the lowest detectable titer, is considered to indicate seropositivity with regards to the presence of poliovirus neutralizing antibodies. Seroconversion is defined as either seronegative participants (\<1:8 titers) who become seropositive (≥1:8) or participants who demonstrate a 4-fold change in titers between two specimens, e.g. a change from 1:8 to 1:32. To compare the immunogenicity across study arms, the investigators will compare the proportion of participants who seroconvert by 18 weeks of age. Chi-square tests will be used to test the statistical significance among seroconversion rates across study arms.
次要结局
- Poliovirus shedding in stool(At 19 weeks of age)