Safety of and Immune Response to an H1N1 Influenza Vaccine in HIV Infected Pregnant Women - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00992017

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 will test 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 II

Study Type:	Interventional
Study Design:	Prevention, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase II Study to Assess the Safety and Immunogenicity of an Inactivated Swine-Origin H1N1 Influenza Vaccine in HIV-1 Infected Pregnant Women

Resource links provided by NLM:

MedlinePlus related topics: AIDS Flu

Drug Information available for: Influenza Vaccines

U.S. FDA Resources

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

Primary Outcome Measures:

Adverse events of all grades [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Adverse events of all grades attributed to the study vaccine [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Withholding of second vaccine dose due to adverse reactions attributed to first dose [ Time Frame: Measured at Day 21 ] [ Designated as safety issue: Yes ]
Immunologic response, defined as hemagglutination inhibition (HAI) titer of at least 1:40 [ Time Frame: Measured at 21 days after first dose and at 10 days after second dose of study vaccine ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Maternal immunologic response, defined as HAI of at least 1:40 [ Time Frame: Measured at 21 days after the second dose of study vaccine, delivery of the baby, and at 3 months and 6 months after delivery ] [ Designated as safety issue: No ]
Infant HAI of at least 1:40 [ Time Frame: Measured at birth (via cord blood) and at 3 months and 6 months of age ] [ Designated as safety issue: No ]
Maternal geometric mean antibody titers (GMT) 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 ]
Infant GMT HAI [ Time Frame: Measured at birth and at 3 and 6 months of age ] [ Designated as safety issue: No ]
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, and at 3 months after delivery ] [ Designated as safety issue: No ]
CD4 count [ Time Frame: Measured at entry and at time of second dose ] [ Designated as safety issue: No ]
HIV RNA copies/ml [ Time Frame: Measured at entry, at 10 days after second dose, at delivery, and at 3 and 6 months after delivery ] [ Designated as safety issue: No ]
Response to seasonal trivalent influenza vaccine (TIV) [ Time Frame: Measured at entry ] [ Designated as safety issue: No ]

Estimated Enrollment:	130
Study Start Date:	September 2009

Arms	Assigned Interventions
H1N1 vaccine: Experimental All participants will receive 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 particularly susceptible to influenza viruses, and appear to be at increased risk of the H1N1 virus. People infected with HIV are at an increased risk of complications from influenza. Both these populations—pregnant women and 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. This study will test 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 will last until 6 months after participants have delivered their babies or up to 52 weeks. Participants will receive two doses of the H1N1 vaccine during pregnancy, delivered at study entry and after 21 days. Each dose will consist of two intramuscular injections (four total injections). On the days of the injections, participants will have their babies' heart rates checked before and after vaccination. At these visits, and on follow-up visits on Days 21, 31, and 42, participants will complete a review of symptoms, physical and neurological exams, and a blood draw. For 10 days after receiving each dose of the vaccine, participants will be asked to keep track of their temperature and symptoms or reactions in a journal. Participants will be contacted on Day 2 and Day 10 after the first dose of vaccine is given and on Day 2 after the second dose of vaccine is given.

At delivery of each participant's baby, blood will be drawn from both the mother and umbilical cord. At 3 and 6 months after delivery, participants may come in for follow-up visits involving, for both mother and child, a review of symptoms, brief physical exams, and blood draws.

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 trivalent influenza vaccine (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 non-melanoma 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 adverse event (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, which 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

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

Show 40 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:

Sharon Nachman, MD

State University of New York at Stony Brook

More Information

Additional Information:

Click here for information on the IMPAACT group and for the package insert on the H1N1 vaccine. This link exits the ClinicalTrials.gov site

Publications:

Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team; Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ, Gubareva LV, Xu X, Bridges CB, Uyeki TM. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med. 2009 Jun 18;360(25):2605-15. Epub 2009 May 7. Erratum in: N Engl J Med. 2009 Jul 2;361(1):102.

Jamieson DJ, Honein MA, Rasmussen SA, Williams JL, Swerdlow DL, Biggerstaff MS, Lindstrom S, Louie JK, Christ CM, Bohm SR, Fonseca VP, Ritger KA, Kuhles DJ, Eggers P, Bruce H, Davidson HA, Lutterloh E, Harris ML, Burke C, Cocoros N, Finelli L, MacFarlane KF, Shu B, Olsen SJ; Novel Influenza A (H1N1) Pregnancy Working Group. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet. 2009 Aug 8;374(9688):451-8. Epub 2009 Jul 28.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	IMPAACT P1086, 10835
Study First Received:	October 7, 2009
Last Updated:	November 18, 2009
ClinicalTrials.gov Identifier:	NCT00992017 History of Changes
Health Authority:	United States: Food and Drug Administration

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

Vaccine
Pregnant
Perinatal

Additional relevant MeSH terms:

RNA Virus Infections
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Immune System Diseases
Acquired Immunodeficiency Syndrome
Orthomyxoviridae Infections
Infection
Immunologic Deficiency Syndromes

Virus Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
HIV Infections
Sexually Transmitted Diseases
Influenza, Human
Lentivirus Infections
Retroviridae Infections

ClinicalTrials.gov processed this record on November 30, 2009