Clinical trial NCT00992017: Safety of and Immune Response to an H1N1 Influenza Vaccine in HIV Infected Pregnant Women
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
H1N1 Influenza Virus
Keywords: Vaccine
Pregnant
Perinatal
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2009-10-08
Enrollment: 130
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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: 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 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.

Primary outcomes:
measure: The Number of Participants Who Had at Least One Adverse Event (AE)
timeFrame: Measured up to 6 months after delivery
measure: The Number of Participants Who Had at Least One AE Attributed to the Study Vaccine
timeFrame: Measured up to 6 months after delivery
measure: Withholding of Second Vaccine Dose Due to Adverse Reactions Attributed to First Dose
timeFrame: Measured at Day 21
measure: Percent of Pregnant Women With a Hemagglutination Inhibition (HAI) Titer of >= 40
timeFrame: Measured at 21 days after first dose and at 10 days after second dose of study vaccine
Secondary outcomes:
measure: Percent of Pregnant Women With an HAI Titer of >= 40 at Delivery, 3 Months and 6 Months After Delivery
timeFrame: Measured at delivery of the baby, and at 3 months and 6 months after delivery
measure: Percent of Infants With an HAI Titer of >= 40
timeFrame: Measured at birth (via cord blood) and at 3 months and 6 months of age
measure: Maternal Geometric Mean Titers (GMT) of Antibodies HAI
timeFrame: Measured after the first and second doses of the vaccine, at delivery, and at 3 and 6 months after delivery
measure: Infant GMT of Antibodies HAI
timeFrame: Measured at birth and at 3 and 6 months of age
measure: Maternal Cell-mediated Immunity (CMI) Responses, as Measured by B-cell and T-cell Enzyme-linked Immunosorbent Spot (ELISPOT) Assay Values
timeFrame: Measured at entry, at 21 days after first dose of vaccine, at 10 days after second dose
measure: Response to Seasonal Trivalent Influenza Vaccine (TIV)
timeFrame: Measured at entry
Other outcomes:
Locations:
city: Alhambra
country: United States
facility: Usc La Nichd Crs
state: California
city: La Jolla
country: United States
facility: University of California, UC San Diego CRS
state: California
city: Long Beach
country: United States
facility: Miller Children's Hosp. Long Beach CA NICHD CRS
state: California
city: Los Angeles
country: United States
facility: UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
state: California
city: San Francisco
country: United States
facility: Univ. of California San Francisco NICHD CRS
state: California
city: Aurora
country: United States
facility: Univ. of Colorado Denver NICHD CRS
state: Colorado
city: Washington
country: United States
facility: Washington Hosp. Ctr. NICHD CRS
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: South Florida CDTC Ft Lauderdale NICHD CRS
state: Florida
city: Jacksonville
country: United States
facility: Univ. of Florida Jacksonville NICHD CRS
state: Florida
city: Miami
country: United States
facility: Pediatric Perinatal HIV Clinical Trials Unit CRS
state: Florida
city: Tampa
country: United States
facility: USF - Tampa NICHD CRS
state: Florida
city: Chicago
country: United States
facility: Rush Univ. Cook County Hosp. Chicago NICHD CRS
state: Illinois
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago (LCH) CRS
state: Illinois
city: New Orleans
country: United States
facility: Tulane Univ. New Orleans NICHD CRS
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Univ. Baltimore NICHD CRS
state: Maryland
city: Boston
country: United States
facility: Children's Hosp. of Boston NICHD CRS
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center Ped. HIV Program NICHD CRS
state: Massachusetts
city: Worcester
country: United States
facility: WNE Maternal Pediatric Adolescent AIDS CRS
state: Massachusetts
city: Newark
country: United States
facility: Rutgers - New Jersey Medical School CRS
state: New Jersey
city: Bronx
country: United States
facility: Bronx-Lebanon CRS
state: New York
city: Bronx
country: United States
facility: Jacobi Med. Ctr. Bronx NICHD CRS
state: New York
city: New York
country: United States
facility: Metropolitan Hosp. NICHD CRS
state: New York
city: New York
country: United States
facility: Columbia IMPAACT CRS
state: New York
city: Stony Brook
country: United States
facility: SUNY Stony Brook NICHD CRS
state: New York
city: Durham
country: United States
facility: DUMC Ped. CRS
state: North Carolina
city: Philadelphia
country: United States
facility: The Children's Hosp. of Philadelphia IMPAACT CRS
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital CRS
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Hospital CRS
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Research Institute CRS
state: Washington
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico Pediatric HIV/AIDS Research Program CRS
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp. PR NICHD CRS
Study officials:
affiliation: State University of New York at Stony Brook
name: Sharon Nachman, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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
citation: 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.
citation: 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.