H1N1v Vaccination of Pregnant Women: A Longitudinal Cohort Study Characterizing Influenza A H1N1v Vaccination in Pregnant Women

Sponsor

Copenhagen Studies on Asthma in Childhood (Other)

Overall Status

Completed

CT.gov ID

NCT01012557

Collaborator

Novartis (Industry)

296

Enrollment

Locations

Arms

Duration (Months)

148

Patients Per Site

5.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Pregnant women are at particular risk during the imminent H1N1v influenza pandemic. The new H1N1v virus requires urgent political and medical decisions on vaccination strategies in order to minimize severe disease and death from this pandemic. However, there is a lack of evidence to build such decisions upon. A vaccine will be provided in the fourth quarter of 2009, but there is little knowledge on the immunogenicity. Particularly its clinical effectiveness and duration of immunity in pregnant women and their newborn infants is unknown. Therefore, it will be important to study the optimal vaccination regimens with respect to dosing and use of adjuvant to decide future health policies on vaccination of pregnant women. We have a unique possibility to study these aspects of H1N1v infection in pregnant women in our ongoing unselected, prospective, birth-cohort study recruiting 800 pregnant mothers between Q1- 2009 and Q4-2010. Pregnant women from East-Denmark are being enrolled during the 2nd trimester and their infant will undergo a close clinical follow-up. The H1N1v pandemic is expected to reach Denmark Q4-2009. The timing of this enrollment and the imminent pandemic allows for an "experiment of nature" whereby the first half of the mothers completes pregnancy before the H1N1v pandemic. The other half of this cohort will be pregnant while H1N1v is prevalent in the community and will require H1N1v vaccination. The aim of this randomized, controlled, trial is to compare and evaluate the dose-related immune protection conferred by vaccine and adjuvant (Novartis vaccine Focetria) in pregnant women and non-pregnant women. In addition the protocol will assess the passive immunity conferred to the newborn from these vaccine regimes. The study will provide evidence-based guidance for health policies on vaccination for the population of pregnant women during future H1N1v pandemics.

Condition or Disease	Intervention/Treatment	Phase
H1N1v Influenza	Biological: Focetria Biological: Focetria Biological: Focetria Biological: Focetria	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

296 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Prevention

Official Title:

H1N1v Vaccination of Pregnant Women: A Longitudinal Cohort Study Characterizing Influenza AH1N1v Vaccination in Pregnant Women

Study Start Date :

Nov 1, 2009

Actual Primary Completion Date :

Sep 1, 2010

Actual Study Completion Date :

Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Pregnant women (>20 weeks), 7.5 mcg H1N1v full MF59 adjuvant	Biological: Focetria 7.5 mcg H1N1v full MF59 adjuvant i.m.(intramuscular)x 1
Active Comparator: Pregnant women (>20 weeks), 3.75 mcg H1N1v half MF59 adjuvant	Biological: Focetria 3.75 mcg H1N1v half MF59 adjuvant i.m.(intramuscular)x 1
Active Comparator: Pregnant women (>20 weeks), 15 mcg H1N1v unadjuvanted	Biological: Focetria 15 mcg N1N1v unadjuvanted i.m.(intramuscular) x 1.
Active Comparator: Non-pregnant mothers, 7.5 mcg H1N1v full MF59 adjuvant	Biological: Focetria 7.5 mcg H1N1v full MF59 adjuvant i.m.(intramuscular) x 1

Outcome Measures

Primary Outcome Measures

Day 22/Day 1, and at all the other relevant time points to assess persistence/Day 1 geometric mean ratio (GMR) of HI [Day 1, Day 22]
Geometric mean HI titer (GMT) on Day 1, Day 22, and at all the other relevant time points to assess persistence. [Day 1, Day 22]
Percentage of subjects achieving a seroconversion or a significant increase (defined as: HI ≥1:40 for subjects negative at baseline [<1:10]; a minimum 4-fold increase in HI titer for subjects positive at baseline [HI≥1:10]) [Day 1, Day 22]
Percentage of subjects with a HI titer ≥1:40 (i.e. seroprotection) on Day 1, Day 22, and at all the other relevant time points to assess persistence [Day 1, Day 22]

Secondary Outcome Measures

The safety of the study vaccines will be assessed based on number of subjects exposed to study vaccines with reported selected adverse events per vaccine group. [12 months]
The outcomes of pregnancies will be categorized as normal, abnormal or therapeutic/elective termination [duration of pregnancy]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy pregnant and non pregnant women living in Eastern Denmark
Fluent in Danish

Exclusion Criteria:

Heart disease, endocrine disease, tuberculosis and sarcoidosis.
History of any anaphylaxis, serious vaccine reactions, or hypersensitivity to influenza viral proteins, to any excipients, and to eggs (including ovalbumin), and chicken proteins.