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

NCT ID: NCT00992017

Last Updated: 2021-11-05

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

130 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-10-31

Study Completion Date

2010-11-30

Brief Summary

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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.

Detailed Description

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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).

Conditions

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HIV Infections H1N1 Influenza Virus

Keywords

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Vaccine Pregnant Perinatal

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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H1N1 vaccine

Pregnant women enrolled received two doses of H1N1 vaccine, administered 21 days apart.

Group Type EXPERIMENTAL

Influenza A (H1N1) monovalent vaccine

Intervention Type BIOLOGICAL

Two 15-microgram intramuscular vaccine injections given together form one dose; two doses (four total injections) are given 21 days apart

Interventions

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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

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* 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.


* 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

* 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


* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

39 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sharon Nachman, MD

Role: STUDY_CHAIR

State University of New York at Stony Brook

Locations

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Usc La Nichd Crs

Alhambra, California, United States

Site Status

University of California, UC San Diego CRS

La Jolla, California, United States

Site Status

Miller Children's Hosp. Long Beach CA NICHD CRS

Long Beach, California, United States

Site Status

UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS

Los Angeles, California, United States

Site Status

Univ. of California San Francisco NICHD CRS

San Francisco, California, United States

Site Status

Univ. of Colorado Denver NICHD CRS

Aurora, Colorado, United States

Site Status

Washington Hosp. Ctr. NICHD CRS

Washington D.C., District of Columbia, United States

Site Status

South Florida CDTC Ft Lauderdale NICHD CRS

Fort Lauderdale, Florida, United States

Site Status

Univ. of Florida Jacksonville NICHD CRS

Jacksonville, Florida, United States

Site Status

Pediatric Perinatal HIV Clinical Trials Unit CRS

Miami, Florida, United States

Site Status

USF - Tampa NICHD CRS

Tampa, Florida, United States

Site Status

Rush Univ. Cook County Hosp. Chicago NICHD CRS

Chicago, Illinois, United States

Site Status

Ann & Robert H. Lurie Children's Hospital of Chicago (LCH) CRS

Chicago, Illinois, United States

Site Status

Tulane Univ. New Orleans NICHD CRS

New Orleans, Louisiana, United States

Site Status

Johns Hopkins Univ. Baltimore NICHD CRS

Baltimore, Maryland, United States

Site Status

Children's Hosp. of Boston NICHD CRS

Boston, Massachusetts, United States

Site Status

Boston Medical Center Ped. HIV Program NICHD CRS

Boston, Massachusetts, United States

Site Status

WNE Maternal Pediatric Adolescent AIDS CRS

Worcester, Massachusetts, United States

Site Status

Rutgers - New Jersey Medical School CRS

Newark, New Jersey, United States

Site Status

Metropolitan Hosp. NICHD CRS

New York, New York, United States

Site Status

Columbia IMPAACT CRS

New York, New York, United States

Site Status

SUNY Stony Brook NICHD CRS

Stony Brook, New York, United States

Site Status

Bronx-Lebanon CRS

The Bronx, New York, United States

Site Status

Jacobi Med. Ctr. Bronx NICHD CRS

The Bronx, New York, United States

Site Status

DUMC Ped. CRS

Durham, North Carolina, United States

Site Status

The Children's Hosp. of Philadelphia IMPAACT CRS

Philadelphia, Pennsylvania, United States

Site Status

St. Jude Children's Research Hospital CRS

Memphis, Tennessee, United States

Site Status

Texas Children's Hospital CRS

Houston, Texas, United States

Site Status

Seattle Children's Research Institute CRS

Seattle, Washington, United States

Site Status

University of Puerto Rico Pediatric HIV/AIDS Research Program CRS

San Juan, , Puerto Rico

Site Status

San Juan City Hosp. PR NICHD CRS

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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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. doi: 10.1056/NEJMoa0903810. Epub 2009 May 7.

Reference Type BACKGROUND
PMID: 19423869 (View on PubMed)

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. doi: 10.1016/S0140-6736(09)61304-0. Epub 2009 Jul 28.

Reference Type BACKGROUND
PMID: 19643469 (View on PubMed)

S. Nachman, A. Weinberg, P. Muresan, M. Abzug, R. Ebiasah, E. Petzold, B. Heckman, H. Watts, J. Miller and M. Levin Safety of an Inactivated Influenza A (H1N1) 2009 Monovalent Vaccine (H1N1 vaccine) in HIV-1 Infected Pregnant Women, P1086. Presented at the Retroviruses Conference, Feb 2010

Reference Type RESULT

Weinberg A, Muresan P, Fenton T, Handelsman E, Watts H, Miller J, Heckman B, Bloom A, Ebiasah R, Petzold E, Levy W, Abzug M, Levin M and Nachman S for IMPAACT P1086 Team: Safety and Immunogenicity of Two Doses of Monovalent Pandemic H1N1 (pH1N1) Influenza Vaccine in HIV-Infected Pregnant Women. Presented at the IDSA conference, October 2010.

Reference Type RESULT

Abzug MJ, Nachman SA, Muresan P, Handelsman E, Watts DH, Fenton T, Heckman B, Petzold E, Weinberg A, Levin MJ; International Maternal Pediatric Adolescent AIDS Clinical Trials Group P1086 Protocol Team. Safety and immunogenicity of 2009 pH1N1 vaccination in HIV-infected pregnant women. Clin Infect Dis. 2013 May;56(10):1488-97. doi: 10.1093/cid/cit057. Epub 2013 Feb 1.

Reference Type DERIVED
PMID: 23378284 (View on PubMed)

Related Links

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http://www.impaactgroup.org

Click here for information on the IMPAACT group and for the package insert on the H1N1 vaccine.

http://rsc.tech-res.com/safetyandpharmacovigilance/gradingtables.aspx

Click here for the table used for grading toxicities: DAIDS Grading Severity of AEs, V1.0, Dec04

Other Identifiers

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10835

Identifier Type: REGISTRY

Identifier Source: secondary_id

IMPAACT P1086

Identifier Type: -

Identifier Source: secondary_id

P1086

Identifier Type: -

Identifier Source: org_study_id