Clinical trial NCT02286895: Immune Response to Rotavirus Vaccine After a Supplemental Dose Given at 9 Months of Age With Local EPI Vaccines in Mali
Official title: An Evaluation of the Immune Response to Pentavalent Rotavirus Vaccine After a Supplemental Dose Given at 9 Months of Age With Local EPI Vaccines in Mali
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diarrhea Rotavirus
Keywords: rotavirus
rotavirus vaccine
Mali
EPI vaccines
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: Center for Vaccine Development - Mali
name: University of Maryland
First posted: 2014-11-10
Enrollment: 600
Sex: ALL
Minimum age (years): 9
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is an evaluation of the immune response to pentavalent rotavirus vaccine (PRV) after an additional fourth dose is given at 9 months of age with local World Health Organization (WHO) Expanded Programme on Immunization (EPI) vaccines in Mali.

Detailed description: Vaccination is the best way to prevent severe rotavirus disease and the deadly, dehydrating diarrhea that it causes. However, given only moderate efficacy in the first year of life and a possible further decline in immunity, it is considered a top priority by public health experts to evaluate the possible value of a "booster" dose of rotavirus vaccine in low income countries to confer longer duration of protection into the second year of life when disease burden continues to be high.

This study is an open-label, individual-randomized, parallel-group, comparative immunogenicity trial. Participating infants randomized to Group A will receive one dose each of measles vaccine (MV), yellow fever vaccine (YFV), and meningitis conjugate vaccine (PsA-TT-5μg) at 9 months of age, and infants randomized to Group B will receive one dose each of MV, YFV, PsA-TT-5μg, and PRV at 9 months of age.

The study will simultaneously evaluate two primary objectives, one for noninferiority of the response to MV given with PRV (co-primary objective 1) and one for noninferiority of the response to YFV given with PRV (co-primary objective 2).

Secondary objectives of the study were the following:

1. To evaluate the non-inferiority of the immune response 3 months post-vaccination (as sero-conversion) to MV given with PRV (Group B) to that given without PRV (Group A).
2. To compare the immune response (as geometric mean titers \[GMTs\]) to YFV given with PRV (Group B) to that given without PRV (Group A).
3. To evaluate the non-inferiority of the immune response (as sero-response) to PsA-TT-5μg given with PRV (Group B) compared to that given without PRV (Group A).
4. To compare the immune response (as GMTs) to PsA-TT-5μg given with PRV (Group B) to that given without PRV (Group A).
5. To evaluate the superiority of the immune response (as sero-response and geometric mean concentrations \[GMCs\]) to a supplemental dose of PRV given at 9 months of age with local EPI vaccines (Group B) compared no supplemental dose (Group A).
6. To describe the safety profile of study vaccination with PRV.

Eligibility criteria: Inclusion Criteria:

* At least 9 months of age through 11 months of age (has not yet reached 1st birthday) at the time of administration of study vaccines.
* Residence in the study area.
* At least one parent or guardian who is at least 18 years of age and is willing to provide written informed consent.
* Generally healthy and free of obvious health problems as established by medical history including physical examination and clinical judgment of the investigator.
* A child who is fully vaccinated according to the local EPI schedule (exclusive of oral polio vaccine birth dose).
* A parent or guardian is willing to attend all planned study visits or allow home visits and mobile phone contacts, as required by the protocol.

Exclusion Criteria:

* Previous receipt any measles-containing vaccine.
* Previous receipt of any yellow fever vaccine.
* Previous receipt of any meningitis vaccine.
* Receipt of rotavirus vaccine within the past 90 days.
* Administration of any other vaccine within 8 weeks prior to administration of study vaccines or planned vaccination during the 4 weeks after study vaccination.
* History of allergic disease or known hypersensitivity to any component of the study vaccines and/or following administration of vaccines included in the local program of immunization
* Use of any investigational or non-registered drug within 90 days prior to the administration of study vaccines.
* Administration of immunoglobulins and/or any blood products within 90 days prior to the administration of study vaccines or planned administration during the vaccine period.
* Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying agents since birth (including systemic corticosteroids, this means prednisone, or equivalent, ≥0.5 mg/kg/day; topical steroids including inhaled steroids are allowed).
* A family history of congenital or hereditary immunodeficiency.
* History of intussusception.
* Uncorrected congenital malformation of the gastrointestinal tract that would predispose for intussusception.
* Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by medical history or physical examination, which in the opinion of the investigator, might interfere with the study objectives.
* Acute illness at the time of enrollment (acute disease is defined as the presence of a moderate or severe illness with fever \[axillary temperature ≥38°C\] or without fever \[severity determined at the discretion of the investigator\]. Acute illness is a temporary exclusion.
* Any condition or criterion that in the opinion of the investigator might compromise the well-being of the subject or the compliance with study procedures or interfere with the outcome of the study.

Primary outcomes:
measure: Number/Percentage of Subjects With Seroconversion for Anti-measles Immunoglobulin G (IgG) Antibody
timeFrame: 28 days post-vaccination
measure: Number/Percentage of Subjects With Seroresponses for Yellow Fever Neutralizing Antibody
timeFrame: 28 days post-vaccination
Secondary outcomes:
measure: Number/Percentage of Subjects With Seroconversion for Anti-measles Immunoglobulin G (IgG) Antibody
timeFrame: 3 months post-vaccination
measure: Serum Neutralization Geometric Mean Titers for Yellow Fever Vaccine
timeFrame: 28 days post-vaccination
measure: Number/Percentage of Subjects With Seroresponses for Meningitis Conjugate Serum Bactericidal Antibody (SBA)
timeFrame: 28 days post-vaccination
measure: Geometric Mean of Meningitis Serum Bactericidal Antibody Titer
timeFrame: Baseline to Day 28
measure: Number/Percentage of Subjects With Anti-rotavirus Immunoglobulin A (IgA) Titer at Least 3 Times Baseline Value
timeFrame: 28 days post-vaccination
measure: Number/Percentage of Subjects With Anti-rotavirus IgA Titer of ≥20 Units/mL
timeFrame: 28 days post-vaccination
measure: Number/Percentage of Subjects With Anti-rotavirus IgA <20 Units/mL at Baseline Visit That Had >=20 Units/mL at Day 28
timeFrame: 28 days post-vaccination
measure: Number/Percentage of Subjects With Anti-rotavirus IgG Titer at Least 3 Times Baseline Value
timeFrame: 28 days post-vaccination
measure: Number/Percentage of Subjects With Anti-rotavirus IgG Titer of ≥20 Units/mL
timeFrame: 28 days post-vaccination
measure: Number/Percentage of Subjects With Anti-rotavirus IgG <20 Units/mL at Baseline Visit That Had >=20 Units/mL at Day 28
timeFrame: 28 days post-vaccination
measure: Geometric Mean of Anti-rotavirus IgA Concentration
timeFrame: 28 days post-vaccination
measure: Geometric Mean of Anti-rotavirus IgG Concentration
timeFrame: 28 days post-vaccination
measure: Geometric Mean of Anti-rotavirus IgA Among Subjects With <20 Units/mL Concentration at Baseline
timeFrame: 28 days post-vaccination
measure: Geometric Mean of Anti-rotavirus IgG Among Subjects With <20 Units/mL Concentration at Baseline
timeFrame: 28 days post-vaccination
measure: Number/Percentage of Participants Experiencing Immediate Reactions Post-vaccination
timeFrame: Within 30 minutes post-vaccination
measure: Number of Solicited Adverse Reactions (AR) Experienced by Participants
timeFrame: 7 days post-vaccination
measure: Number/Percentage of Participants Experiencing Serious Adverse Events (SAE)
timeFrame: 3 months post-vaccination
Other outcomes:
Locations:
city: Bamako
country: Mali
facility: CVD-Mali
Study officials:
affiliation: Center for Vaccine Development - Mali
name: Samba O Sow, MD, Msc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Haidara FC, Tapia MD, Sow SO, Doumbia M, Coulibaly F, Diallo F, Traore A, Kodio M, Kelly CL, Fitzpatrick M, Kotloff K, Victor JC, Neuzil K. Evaluation of a Booster Dose of Pentavalent Rotavirus Vaccine Coadministered With Measles, Yellow Fever, and Meningitis A Vaccines in 9-Month-Old Malian Infants. J Infect Dis. 2018 Jul 13;218(4):606-613. doi: 10.1093/infdis/jiy215.