Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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: October 28, 2014
Last verified: October 2014
  Purpose

Both pregnant women and people infected with HIV are at increased risk of viral infection, including influenza infection. Pregnant women infected with HIV may be at particular risk of infection from the new H1N1 influenza virus. This study tested the safety and immunogenicity of an H1N1 influenza vaccine in pregnant women infected with HIV.


Condition Intervention Phase
HIV Infections
H1N1 Influenza Virus
Biological: Influenza A (H1N1) monovalent vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase II Study to Assess the Safety and Immunogenicity of an Inactivated Monovalent Influenza A (H1N1) Vaccine in HIV-1 Infected Pregnant Women

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

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

  • The Number of Participants Who Had at Least One AE Attributed to the Study Vaccine [ Time Frame: Measured up to 6 months after delivery ] [ Designated as safety issue: Yes ]
    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.

  • Withholding of Second Vaccine Dose Due to Adverse Reactions Attributed to First Dose [ Time Frame: Measured at Day 21 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Infant GMT of Antibodies HAI [ Time Frame: Measured at birth and at 3 and 6 months of age ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Response to Seasonal Trivalent Influenza Vaccine (TIV) [ Time Frame: Measured at entry ] [ Designated as safety issue: No ]
    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.


Enrollment: 130
Study Start Date: October 2009
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: H1N1 vaccine
Pregnant women enrolled received two doses of H1N1 vaccine, administered 21 days apart.
Biological: Influenza A (H1N1) monovalent vaccine
Two 15-microgram intramuscular vaccine injections given together form one dose; two doses (four total injections) are given 21 days apart

Detailed Description:

On June 11, 2009, the World Health Organization declared a pandemic of the new H1N1 influenza virus, after the virus had caused significant fevers and respiratory illnesses in Mexico and the United States. Pregnant women are at an increased risk of complications from influenza. HIV infected people tend to have lower than normal antibody responses to seasonal influenza vaccines. Data suggest that larger than average doses of a vaccine counteract a weak antibody response. Preliminary results from ongoing studies of influenza A (H1N1) 2009 monovalent vaccines indicate that the vaccine may increase immune activation. This study tested the safety and antibody response of high doses of the influenza A (H1N1) 2009 monovalent vaccine in pregnant women infected with HIV.

Participation in this study lasted until 6 months after participants had delivered their babies or up to 52 weeks. Participants received two doses of the H1N1 vaccine at study entry and after 21 days. Each dose consisted of two intramuscular injections (four total injections). On the days of the injections, participants had their babies' heart rates checked before and after vaccination. At these visits, and at follow-up visits on Days 21, 31, and 42, participants completed a review of symptoms, physical and neurological exams, and a blood draw. For 10 days after receiving each dose of the vaccine, participants were asked to keep track of their temperatures and symptoms or reactions in a journal. Participants were contacted on Day 2 and Day 10 after the first dose of vaccine was given and on Day 2 after the second dose of vaccine was given. Some participants also received a phone call after 6 months.

At delivery of each participant's baby, blood was drawn from both the mother and umbilical cord (or from the baby if the cord blood could not be obtained). At 3 and 6 months after delivery, participants came in for follow-up visits involving, for both mother and child, a review of symptoms, brief physical exams, and blood draws (at 6 months only some women had a clinic visit, the rest received a phone call).

  Eligibility

Ages Eligible for Study:   18 Years to 39 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for Step I:

  • Confirmed diagnosis of HIV-1 infection
  • Pregnant
  • Between 14 and 35 weeks of gestation
  • Documented platelet count of greater than 50,000 mm3 and an absolute neutrophil count (ANC) of greater than 500 mm3 within 28 days prior to study entry
  • Able to understand and comply with planned study procedures
  • On antiretroviral therapy (ART) as outlined in the treatment guidelines for pregnant HIV-1 infected women. Women must be currently taking ART or should initiate ART either prior to or concomitantly with the first dose of the vaccine.

Inclusion Criteria for Step II:

  • Received the first dose of influenza A (H1N1) 2009 monovalent vaccine
  • Has a documented platelet count of greater than 50,000 mm3 and an ANC of greater than 500 mm3 within the 28 days prior to Step II entry

Exclusion Criteria for Step I:

  • Has a known allergy to eggs, egg products, neomycin, or polymyxin
  • Has a history, in the opinion of the site investigator, of severe reactions following previous immunization with seasonal TIV
  • Participation in a novel H1N1 influenza vaccine study in the past 2 years
  • Proven history, by reverse transcription polymerase chain reaction (RT-PCR), of novel influenza H1N1 infection or positive influenza diagnostic test since June 2009 (specificity to H1N1 not required) prior to study entry
  • Received any other live licensed vaccine within 4 weeks or inactivated licensed vaccine within 2 weeks prior to study entry
  • Received a nonlicensed agent (vaccine, drug, biologic, device, blood product, or medication) within 4 weeks prior to vaccination in this study or expects to receive another nonlicensed agent before delivery
  • Acute illness and/or an oral temperature greater than or equal to 100.0 degrees F within 24 hours prior to study entry
  • Use of anti-cancer chemotherapy or radiation therapy within the preceding 36 months of study enrollment or has immunosuppression as a result of an underlying illness or treatment (other than HIV-1 infection)
  • Active neoplastic disease (excluding nonmelanoma skin cancer, human papillomavirus [HPV]-related cervical dysplasia, and cervical intraepithelial neoplasia [CIN] Grades 1, 2, or 3)
  • Long-term use of glucocorticoids, including oral or parenteral prednisone or equivalent (at least 2.0 mg/kg per day or at least 20 mg total dose) for more than 2 consecutive weeks (or 2 weeks total) in the past 3 months or high-dose inhaled steroids (more than 800 mcg/day of beclomethasone dipropionate or equivalent) within the past 3 months. Nasal and topical steroids are allowed.
  • Received immunoglobulin or other blood products (with exception of Rho D immune globulin) within the 3 months prior to enrollment in this study
  • Current diagnosis of uncontrolled major psychiatric disorder
  • History of Guillain-Barre syndrome in the subject or subject's family (including parents, siblings, half-siblings, or children)
  • Onset of a neurological disorder including (but not limited to) absent ankle and patellar deep tendon reflexes (DTRs) in both legs (all four absent) within the past 6 months
  • Disproportionate loss of strength in lower extremity or extremities compared to the upper extremities (not thought to be related to pregnancy) within the past 6 months
  • Any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol. Pregnancy complications such as preterm labor, hypertension and pre-eclampsia are not exclusion criteria for this study.

Exclusion Criteria for Step II:

  • Received a nonlicensed agent (vaccine, drug, biologic, device, blood product, or medication), other than from participation in this study, since the study vaccine dose #1 or expects to receive another nonlicensed agent before delivery
  • Use of anti-cancer chemotherapy or radiation therapy since study vaccine dose #1, new diagnosis of an active malignancy, or is immunosuppressed as a result of an underlying illness (other than HIV-1 infection) or treatment
  • Use of glucocorticoids, including oral or parenteral prednisone or equivalent (at least 2.0 mg/kg per day or at least 20 mg total dose) or high-dose inhaled steroids (more than 800 mcg/day of beclomethasone dipropionate or equivalent) for more than 2 consecutive weeks (or 2 weeks total) since study vaccine dose #1. Nasal and topical steroids are allowed.
  • Received immunoglobulin or other blood products (with exception of Rho D immune globulin) since study vaccine dose #1
  • A new diagnosis of uncontrolled major psychiatric disorder since study vaccine dose #1
  • New occurrence or new awareness of Guillain-Barre syndrome in the subject or subject's family (including parents, siblings, half-siblings, or children) since study vaccine dose #1
  • A new onset of a neurological disorder including (but not limited to) absent ankle and patellar DTRs in both legs (all four absent) since study vaccine dose #1
  • Disproportionate loss of strength in lower extremity or extremities compared to the upper extremities (not thought to be related to pregnancy) since study vaccine dose #1
  • Any Grade 3 toxicity or AE experienced by a participant unless the investigator has received protocol team approval
  • Any Grade 4 toxicity or AE (other than injection site reaction or fever) that is definitely, probably, or possibly related to the study vaccine dose #1
  • Any Grade 4 injection site reactions or fever experienced by a subject, unless the investigator has received protocol team approval
  • Any Grade 4 AEs that are definitely not or probably not related to study vaccine, unless the investigator has received protocol team approval
  • Any new clinical findings since the study vaccine dose #1, that, in the investigator's opinion, would compromise the safety of the participant
  • Participant refuses further vaccination. The subject will still be asked to complete safety visits and be followed in the study.
  • Participant withdraws consent. Participants may withdraw their consent for study participation at any time and for any reason, without penalty.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00992017

  Hide Study Locations
Locations
United States, California
Usc La Nichd Crs
Alhambra, California, United States, 91803
University of California, UC San Diego CRS
La Jolla, California, United States, 92093-0672
Miller Children's Hosp. Long Beach CA NICHD CRS
Long Beach, California, United States, 90806
UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
Los Angeles, California, United States, 90095-1752
Univ. of California San Francisco NICHD CRS
San Francisco, California, United States, 94143
United States, Colorado
Univ. of Colorado Denver NICHD CRS
Aurora, Colorado, United States, 80045
United States, District of Columbia
Washington Hosp. Ctr. NICHD CRS
Washington, District of Columbia, United States, 20010
United States, Florida
South Florida CDTC Ft Lauderdale NICHD CRS
Fort Lauderdale, Florida, United States, 33316
Univ. of Florida Jacksonville NICHD CRS
Jacksonville, Florida, United States, 32209
Pediatric Perinatal HIV Clinical Trials Unit CRS
Miami, Florida, United States, 33136
USF - Tampa NICHD CRS
Tampa, Florida, United States, 33606
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago (LCH) CRS
Chicago, Illinois, United States, 60614-3393
Rush Univ. Cook County Hosp. Chicago NICHD CRS
Chicago, Illinois, United States, 60612
United States, Louisiana
Tulane Univ. New Orleans NICHD CRS
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins Univ. Baltimore NICHD CRS
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Boston Medical Center Ped. HIV Program NICHD CRS
Boston, Massachusetts, United States, 02118
Children's Hosp. of Boston NICHD CRS
Boston, Massachusetts, United States, 02115
WNE Maternal Pediatric Adolescent AIDS CRS
Worcester, Massachusetts, United States, 01605
United States, New Jersey
Rutgers - New Jersey Medical School CRS
Newark, New Jersey, United States, 07103
United States, New York
Bronx-Lebanon CRS
Bronx, New York, United States, 10457
Jacobi Med. Ctr. Bronx NICHD CRS
Bronx, New York, United States, 10461
Metropolitan Hosp. NICHD CRS
New York, New York, United States, 10029
Columbia IMPAACT CRS
New York, New York, United States, 10032
SUNY Stony Brook NICHD CRS
Stony Brook, New York, United States, 11794-8111
United States, North Carolina
DUMC Ped. CRS
Durham, North Carolina, United States, 27710
United States, Pennsylvania
The Children's Hosp. of Philadelphia IMPAACT CRS
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
St. Jude Children's Research Hospital CRS
Memphis, Tennessee, United States, 38105-3678
United States, Texas
Texas Children's Hospital CRS
Houston, Texas, United States, 77030-2399
United States, Washington
Seattle Children's Research Institute CRS
Seattle, Washington, United States, 98101
Puerto Rico
San Juan City Hosp. PR NICHD CRS
San Juan, Puerto Rico, 00936
University of Puerto Rico Pediatric HIV/AIDS Research Program CRS
San Juan, Puerto Rico, 00935
Sponsors and Collaborators
Investigators
Study Chair: Sharon Nachman, MD State University of New York at Stony Brook
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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: October 28, 2014
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Vaccine
Pregnant
Perinatal

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Influenza, Human
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Orthomyxoviridae Infections
RNA Virus Infections
Respiratory Tract Diseases
Respiratory Tract Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on November 20, 2014