Safety of and Immune Response to an H1N1 Influenza Vaccine in HIV Infected Pregnant Women

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00992017
First received: October 7, 2009
Last updated: July 9, 2014
Last verified: July 2014
Results First Received: November 7, 2011  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Conditions: HIV Infections
H1N1 Influenza Virus
Intervention: Biological: Influenza A (H1N1) monovalent vaccine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Pregnant women were enrolled from 31 sites between October 8, 2009 and November 13, 2009.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Two study participants were enrolled but left the clinic before receiving any vaccination and they were taken off study.

Reporting Groups
  Description
H1N1 Vaccine Pregnant women received two doses of H1N1 vaccine administered 21 days apart. Each dose consisted of two 15-microgram intramuscular injections.

Participant Flow:   Overall Study
    H1N1 Vaccine  
STARTED     128 [1]
Received Both Study Vaccinations     124  
Received Only One Study Vaccination     4 [2]
COMPLETED     118  
NOT COMPLETED     10  
Lost to Follow-up                 2  
Withdrawal by Subject                 2  
Unable to get to clinic                 5  
Not adhere to study requirements                 1  
[1] Two additional women were enrolled but left the clinic before vaccine was administered.
[2] Reasons: delivered and LFU; moved; no transportation; ineligible - blood transfusion at delivery



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
H1N1 Vaccine Pregnant women received two doses of H1N1 vaccine administered 21 days apart. Each dose consisted of two 15-microgram intramuscular injections.

Baseline Measures
    H1N1 Vaccine  
Number of Participants  
[units: participants]
  128  
Age  
[units: years]
Mean ± Standard Deviation
  28  ± 6  
Gender  
[units: participants]
 
Female     128  
Male     0  
Region of Enrollment  
[units: participants]
 
United States     112  
Puerto Rico     16  
CD4 Cells Count [1]
[units: cells / mm^3]
Mean ± Standard Deviation
  504  ± 264  
Percentage of CD4 Cells [2]
[units: percentage of CD4 cells]
Mean ± Standard Deviation
  30  ± 11  
Gestational Age [3]
[units: Weeks]
Mean ± Standard Deviation
  25  ± 6  
[1] This measures the number of CD4 cells.
[2] This measures the percentage of CD4 cells.
[3] This shows the approximate gestational age at study entry.



  Outcome Measures
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1.  Primary:   The Number of Participants Who Had at Least One Adverse Event (AE)   [ Time Frame: Measured up to 6 months after delivery ]

Measure Type Primary
Measure Title The Number of Participants Who Had at Least One Adverse Event (AE)
Measure Description Shows the number of participants who had at least one adverse event (AE) in each category. These include: abnormal laboratory values, signs and symptoms, or diagnoses; solicited local AEs; and solicited systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Time Frame Measured up to 6 months after delivery  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All 128 pregnant women who received at least one vaccination are included in this analysis.

Reporting Groups
  Description
H1N1 Vaccine Pregnant women enrolled in the study.

Measured Values
    H1N1 Vaccine  
Number of Participants Analyzed  
[units: participants]
  128  
The Number of Participants Who Had at Least One Adverse Event (AE)  
[units: Participants]
 
Overall (New AEs after start of treatment)     118  
Grade 4 AEs (New, after start of treatment)     11  
Grade 3 AEs (New, after start of treatment)     8  
Grade >=2 local and systemic AEs to injection     0  

No statistical analysis provided for The Number of Participants Who Had at Least One Adverse Event (AE)



2.  Primary:   The Number of Participants Who Had at Least One AE Attributed to the Study Vaccine   [ Time Frame: Measured up to 6 months after delivery ]

Measure Type Primary
Measure Title The Number of Participants Who Had at Least One AE Attributed to the Study Vaccine
Measure Description Shows the number of participants who experienced any events that were thought to be at least possibly related to study treatment. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Time Frame Measured up to 6 months after delivery  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All 128 pregnant women who received at least one vaccination are included.

Reporting Groups
  Description
Vaccinated Study Participants Pregnant women who received at least one H1N1 vaccination.

Measured Values
    Vaccinated Study Participants  
Number of Participants Analyzed  
[units: participants]
  128  
The Number of Participants Who Had at Least One AE Attributed to the Study Vaccine  
[units: Participants]
  0  

No statistical analysis provided for The Number of Participants Who Had at Least One AE Attributed to the Study Vaccine



3.  Primary:   Withholding of Second Vaccine Dose Due to Adverse Reactions Attributed to First Dose   [ Time Frame: Measured at Day 21 ]

Measure Type Primary
Measure Title Withholding of Second Vaccine Dose Due to Adverse Reactions Attributed to First Dose
Measure Description No text entered.
Time Frame Measured at Day 21  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All 128 pregnant women who received at least one vaccination are included.

Reporting Groups
  Description
Vaccinated Study Participants Pregnant women who received at least one H1N1 vaccination.

Measured Values
    Vaccinated Study Participants  
Number of Participants Analyzed  
[units: participants]
  128  
Withholding of Second Vaccine Dose Due to Adverse Reactions Attributed to First Dose  
[units: Participants]
  0  

No statistical analysis provided for Withholding of Second Vaccine Dose Due to Adverse Reactions Attributed to First Dose



4.  Primary:   Percent of Pregnant Women With a Hemagglutination Inhibition (HAI) Titer of >= 40   [ Time Frame: Measured at 21 days after first dose and at 10 days after second dose of study vaccine ]

Measure Type Primary
Measure Title Percent of Pregnant Women With a Hemagglutination Inhibition (HAI) Titer of >= 40
Measure Description Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280. Seroprotection was defined as having a titer of >=40 following vaccination.
Time Frame Measured at 21 days after first dose and at 10 days after second dose of study vaccine  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis population consists of the eligible pregnant women with nonmissing HAI titers, who had not delivered prior to the evaluation, and had received all doses of vaccine up to that timepoint. The N for the analyses of HAI titers after the first and second vaccinations were 118 and 108, respectively.

Reporting Groups
  Description
H1N1 Vaccine The pregnant women who received the H1N1 vaccinations.

Measured Values
    H1N1 Vaccine  
Number of Participants Analyzed  
[units: participants]
  118  
Percent of Pregnant Women With a Hemagglutination Inhibition (HAI) Titer of >= 40  
[units: Percent of participants]
Number ( 95% Confidence Interval )
 
Percent with titers >= 40 post dose 1 (N=118)     73.7  
  ( 64.8 to 81.4 )  
Percent with titers >= 40 post dose 2 (N=108)     80.6  
  ( 71.8 to 87.5 )  

No statistical analysis provided for Percent of Pregnant Women With a Hemagglutination Inhibition (HAI) Titer of >= 40



5.  Secondary:   Percent of Pregnant Women With an HAI Titer of >= 40 at Delivery, 3 Months and 6 Months After Delivery   [ Time Frame: Measured at delivery of the baby, and at 3 months and 6 months after delivery ]

Measure Type Secondary
Measure Title Percent of Pregnant Women With an HAI Titer of >= 40 at Delivery, 3 Months and 6 Months After Delivery
Measure Description Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280. Seroprotection was defined as having a titer of >=40 following vaccination.
Time Frame Measured at delivery of the baby, and at 3 months and 6 months after delivery  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The population consists of eligible pregnant women with nonmissing HAI titers, who had not delivered before the evaluation post second dose, and received two doses of vaccine. The N for the analyses of HAI titers at delivery, and at 3 and 6 months after were 102, 92 and 58, respectively. Only some women had a clinic visit at 6 months post delivery.

Reporting Groups
  Description
H1N1 Vaccine Pregnant women who received H1N1 vaccinations.

Measured Values
    H1N1 Vaccine  
Number of Participants Analyzed  
[units: participants]
  102  
Percent of Pregnant Women With an HAI Titer of >= 40 at Delivery, 3 Months and 6 Months After Delivery  
[units: Percent of participants]
Number ( 95% Confidence Interval )
 
% with titers >= 1:40 at delivery (N=102)     65.7  
  ( 55.6 to 74.8 )  
% with titers >= 1:40 at 3 mo post delivery (N=92)     55.4  
  ( 44.7 to 65.8 )  
% with titers >= 1:40 at 6 mo post delivery (N=58)     60.3  
  ( 46.6 to 73.0 )  

No statistical analysis provided for Percent of Pregnant Women With an HAI Titer of >= 40 at Delivery, 3 Months and 6 Months After Delivery



6.  Secondary:   Percent of Infants With an HAI Titer of >= 40   [ Time Frame: Measured at birth (via cord blood) and at 3 months and 6 months of age ]

Measure Type Secondary
Measure Title Percent of Infants With an HAI Titer of >= 40
Measure Description Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280. Seroprotection was defined as having a titer of >=40 following vaccination.
Time Frame Measured at birth (via cord blood) and at 3 months and 6 months of age  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The population consists of infants born to eligible women with nonmissing HAI titers, who had not delivered before the evaluation post second dose, and received two doses of vaccine. The N for analyses at birth, 3 and 6 months were 96, 87 and 52, respectively. Cord blood was used when available. Only some infants had a clinic visit at 6 months.

Reporting Groups
  Description
Infants Infants born to pregnant women who received H1N1 vaccines.

Measured Values
    Infants  
Number of Participants Analyzed  
[units: participants]
  96  
Percent of Infants With an HAI Titer of >= 40  
[units: Percent of participants]
Number ( 95% Confidence Interval )
 
% infants with titers >= 1:40 at birth (N=96)     64.6  
  ( 54.2 to 74.1 )  
% infants with titers >= 1:40 at 3 months (N=87)     23.0  
  ( 14.6 to 33.2 )  
% infants with titers >= 1:40 at 6 months (N=52)     11.5  
  ( 4.4 to 23.4 )  

No statistical analysis provided for Percent of Infants With an HAI Titer of >= 40



7.  Secondary:   Maternal Geometric Mean Titers (GMT) of Antibodies HAI   [ Time Frame: Measured after the first and second doses of the vaccine, at delivery, and at 3 and 6 months after delivery ]

Measure Type Secondary
Measure Title Maternal Geometric Mean Titers (GMT) of Antibodies HAI
Measure Description Presents the value of the geometric mean titer at each time point. Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280.
Time Frame Measured after the first and second doses of the vaccine, at delivery, and at 3 and 6 months after delivery  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The population consists of eligible women with nonmissing HAI titers, who had not delivered before the evaluation post first or second dose, and received all vaccines up to that point, respectively. The N for analyses after the first and second vaccinations, at delivery, 3 and 6 months after were 104, 94, 102, 92 and 58, respectively.

Reporting Groups
  Description
H1N1 Vaccine Pregnant women who received the H1N1 vaccines.

Measured Values
    H1N1 Vaccine  
Number of Participants Analyzed  
[units: participants]
  104  
Maternal Geometric Mean Titers (GMT) of Antibodies HAI  
[units: titers]
Geometric Mean ( 95% Confidence Interval )
 
Post first vaccination (N=104)     83  
  ( 63 to 110 )  
Post second vaccination (N=94)     81  
  ( 62 to 106 )  
At delivery (N=102)     50  
  ( 39 to 65 )  
At 3 months post delivery (N=92)     36  
  ( 28 to 46 )  
At 6 months post delivery (N=58)     38  
  ( 29 to 50 )  

No statistical analysis provided for Maternal Geometric Mean Titers (GMT) of Antibodies HAI



8.  Secondary:   Infant GMT of Antibodies HAI   [ Time Frame: Measured at birth and at 3 and 6 months of age ]

Measure Type Secondary
Measure Title Infant GMT of Antibodies HAI
Measure Description Presents the value of the geometric mean titer at each time point. Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280.
Time Frame Measured at birth and at 3 and 6 months of age  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The population consists of infants born to eligible women with nonmissing HAI titers, who had not delivered before the evaluation post second dose, and received two doses of vaccine. The N for analyses at birth, 3 and 6 months were 96, 87 and 52, respectively. Cord blood was used when available. Only some infants had a clinic visit at 6 months.

Reporting Groups
  Description
Infants Infants born to pregnant women who received H1N1 vaccines.

Measured Values
    Infants  
Number of Participants Analyzed  
[units: participants]
  96  
Infant GMT of Antibodies HAI  
[units: units on the HAI titer scale]
Geometric Mean ( 95% Confidence Interval )
 
At birth (N=96 infants)     56  
  ( 43 to 72 )  
At 3 months (N=87 infants)     13  
  ( 11 to 16 )  
At 6 months (N=52 infants)     14  
  ( 11 to 17 )  

No statistical analysis provided for Infant GMT of Antibodies HAI



9.  Secondary:   Maternal Cell-mediated Immunity (CMI) Responses, as Measured by B-cell and T-cell Enzyme-linked Immunosorbent Spot (ELISPOT) Assay Values   [ Time Frame: Measured at entry, at 21 days after first dose of vaccine, at 10 days after second dose ]

Measure Type Secondary
Measure Title Maternal Cell-mediated Immunity (CMI) Responses, as Measured by B-cell and T-cell Enzyme-linked Immunosorbent Spot (ELISPOT) Assay Values
Measure Description The median and interquartile range (IQR) of B-Cell ELISPOT-measured IgG antibody-secreting cells (ASC)/10^6 PBMC and the median and interquartile range (IQR) of T-Cell ELISPOT-measured pH1N1 IFNgamma spot-forming cells (SFC)/10^6 PBMC.
Time Frame Measured at entry, at 21 days after first dose of vaccine, at 10 days after second dose  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The pregnant women who had not delivered prior to the evaluation, had received all doses of vaccine up to that timepoint and had sufficient samples for testing.

Reporting Groups
  Description
H1N1 Vaccine The pregnant women who received the H1N1 vaccinations.

Measured Values
    H1N1 Vaccine  
Number of Participants Analyzed  
[units: participants]
  45  
Maternal Cell-mediated Immunity (CMI) Responses, as Measured by B-cell and T-cell Enzyme-linked Immunosorbent Spot (ELISPOT) Assay Values  
[units: ASC or SFC/10^6 PBMC]
Median ( Inter-Quartile Range )
 
IgG ASC/10^6 PBMC, Week 0 (N=36)     6  
  ( 2 to 28 )  
IgG ASC/10^6 PBMC, Post Dose 1 (N=36)     15  
  ( 4 to 46 )  
IgG ASC/10^6 PBMC, Post Dose 2 (N=39)     14  
  ( 6 to 70 )  
pH1N1 IFNgamma SFC/10^6 PBMC, Week 0 (N=45)     166  
  ( 38 to 324 )  
pH1N1 IFNgamma SFC/10^6 PBMC, Post Dose 1 (N=44)     117  
  ( 40 to 506 )  
pH1N1 IFNgamma SFC/10^6 PBMC, Post Dose 2 (N=43)     76  
  ( 32 to 336 )  

No statistical analysis provided for Maternal Cell-mediated Immunity (CMI) Responses, as Measured by B-cell and T-cell Enzyme-linked Immunosorbent Spot (ELISPOT) Assay Values



10.  Secondary:   Response to Seasonal Trivalent Influenza Vaccine (TIV)   [ Time Frame: Measured at entry ]

Measure Type Secondary
Measure Title Response to Seasonal Trivalent Influenza Vaccine (TIV)
Measure Description Presents the value of the median titer as well as the interquartile range at study entry. Antibodies to seasonal Influenza vaccine were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280.
Time Frame Measured at entry  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pregnant women who received the first H1N1 immunization.

Reporting Groups
  Description
H1N1 Vaccine Pregnant women who received the H1N1 vaccines.

Measured Values
    H1N1 Vaccine  
Number of Participants Analyzed  
[units: participants]
  128  
Response to Seasonal Trivalent Influenza Vaccine (TIV)  
[units: titer]
Median ( Inter-Quartile Range )
  20  
  ( 10 to 40 )  

No statistical analysis provided for Response to Seasonal Trivalent Influenza Vaccine (TIV)




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Melissa Allen, Director, IMPAACT Operations Center
Organization: Family Health International (FHI 360)
phone: 919-405-1429
e-mail: mallen@fhi360.org


Publications:
Publications automatically indexed to this study:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00992017     History of Changes
Other Study ID Numbers: P1086, 10835, IMPAACT P1086
Study First Received: October 7, 2009
Results First Received: November 7, 2011
Last Updated: July 9, 2014
Health Authority: United States: Food and Drug Administration
United States: Federal Government