Safety of and Immune Response to an H1N1 Influenza Virus Vaccine in HIV Infected Children and Youth - 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:	NCT00992836

Purpose

Children and people infected with HIV are particularly susceptible to influenza infections. This study will test the safety and effectiveness of a vaccine for the new H1N1 influenza virus in children and youth infected with HIV.

Condition	Intervention	Phase
HIV Infections H1N1 Influenza Virus	Biological: Influenza A (H1N1) 2009 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 Perinatally Infected Children and Youth

Resource links provided by NLM:

MedlinePlus related topics: AIDS Flu

U.S. FDA Resources

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

Primary Outcome Measures:

Adverse events (AEs) of all grades, including abnormal laboratory values, signs and symptoms, or diagnoses; solicited local AEs; and solicited systemic AEs [ Time Frame: Measured up to 7 months after vaccination ] [ Designated as safety issue: Yes ]
AEs of all grades attributed to the study vaccine [ Time Frame: Measured up to 7 months after vaccination ] [ 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 hemagglutinin inhibition (HAI) titer of at least 1:40 [ Time Frame: Measured at 21 days after first dose and 10 days after second dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

HAI of at least 1:40 at long-term follow-up [ Time Frame: Measured at 6 months after second dose ] [ Designated as safety issue: No ]
Geometric mean antibody titers (GMT) HAI [ Time Frame: Measured after first and second doses and 6 months after second dose ] [ Designated as safety issue: No ]
Cell-mediated immune responses, measured by B-cell and T-cell enzyme-linked immunosorbent spot (ELISPOT) assay values and frequency of cytotoxic T-cell lymphocytes specific for novel H1N1 influenza virus [ Time Frame: Measured after first and second doses, 21 days after first dose, and 10 days and 6 months after second dose ] [ Designated as safety issue: No ]
HAI titers against seasonal influenza viruses containing trivalent influenza vaccine (TIV) [ Time Frame: Measured after first and second doses, 21 days after first dose, and 10 days and 6 months after second dose ] [ Designated as safety issue: No ]
Cell-mediated immune responses to influenza viruses contained in TIV and other antigens [ Time Frame: Measured after first and second doses, 21 days after first dose, and 10 days and 6 months after second dose ] [ Designated as safety issue: No ]

Estimated Enrollment:

140

Arms	Assigned Interventions
Influenza A (H1N1) 2009 monovalent vaccine: Experimental All participants will receive two doses of the H1N1 influenza virus vaccine, administered 21 days apart.	Biological: Influenza A (H1N1) 2009 monovalent vaccine Two doses of vaccine, delivered 21 days apart, with each dose consisting of two 15-microgram intramuscular injections

Detailed Description:

The new H1N1 influenza virus seen in 2009 has been designated a pandemic by the World Health Organization, due to the sustained community outbreaks seen in the United States and Mexico. Based on preliminary data, it appears children and young adults are particularly at risk of the H1N1 virus. People infected with HIV are also more susceptible to severe influenza infections than those who are uninfected. Children with HIV infection, then, have a compounded risk of H1N1 infection. Higher doses of influenza vaccines are associated with the development of higher levels of serum antibodies, which are needed to resist infection. Higher vaccine doses can be used to improve vaccine effectiveness in at-risk populations. This study will test the safety and immune response of HIV infected children and youth to a high dose of a vaccine for the new H1N1 influenza virus.

Participation in this study will last 7 months and have two steps. The first step involves receiving the first dose of H1N1 virus vaccine, and the second step, occurring 21 days later, involves receiving the second dose of vaccine. Each dose of vaccine will be delivered via two intramuscular shots (four total injections). After receiving each dose of the vaccine, participants will be given a diary to record any symptoms or reactions. Participants will be stratified into three groups by age, including 4 to 9 years, 9 to 18 years, and 18 to 25 years.

Participants will complete five scheduled visits, taking place at screening, study entry, Days 21 and 31, and after 7 months. Measurements taken on these visits will include a medical history, physical and neurological exams, a blood draw, and, when applicable, a pregnancy test. In addition to these visits, participants may receive up to three additional phone calls or visits occurring 2 and 10 days after the first dose of vaccine and 2 days after the second dose of vaccine to check for reactions to the vaccine.

Eligibility

Ages Eligible for Study:	4 Years to 25 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria for Step I:

HIV infected
HIV-1 was perinatally acquired, in the opinion of the investigator
Participants receiving antiretrovirals (ARVs) must have been receiving a stable regimen for 90 days prior to entry with no intention to modify their regimen within 60 days following study entry
Participants not receiving ARVs at entry must not have received ARVs within 90 days prior to entry and must NOT plan to initiate ARVs within 60 days following study entry
Ability to complete all study immunizations and evaluations, in the opinion of the investigator
Agrees to use contraception, if necessary
Documented platelet count of more than 50,000 per mm3 and an absolute neutrophil count (ANC) of more than 500 per mm3 within the 30 days prior to study entry
Youth of legal age (from 18 to 25 years of age), parent or legal guardian, or participants who are emancipated minors must provide informed consent

Inclusion Criteria for Step II:

Received the first dose of Influenza A (H1N1) 2009 monovalent vaccine at least 21 days ago
Documented platelet count of more than 50,000 per mm3 and an ANC of more than 500 per mm3 within the 30 days prior to Step II entry
If a woman became pregnant after Dose #1, she must be at more than 14 weeks of gestation and have her obstetrician's permission to receive the vaccine

Exclusion Criteria for Step I:

Pregnancy
Known allergy to egg protein (egg or egg product) or other components in the vaccines (these may include, but are not limited to: neomycin and polymyxin)
History, in the opinion of the site investigator, of severe reactions following previous immunization with seasonal influenza vaccines that would contraindicate receipt of any influenza vaccine.
History of probable or proven pandemic 2009 Influenza A (H1N1) infection prior to study entry
Has received any live licensed vaccine within 4 weeks or inactivated licensed vaccine within 2 weeks prior to study entry
Has received a nonlicensed agent (vaccine, drug, biologic, device, blood product, or medication) within 4 weeks prior to study entry or expects to receive another nonlicensed agent during the course of the study
Has an acute illness or a documented temperature greater than or equal to 100.0 degrees Fahrenheit within 24 hours prior to study entry
Use of anti-cancer chemotherapy or radiation therapy within the 36 months preceding study entry or has immunosuppression as a result of an underlying illness or treatment (other than HIV-1 infection)
Has an active neoplastic disease
Long-term use of glucocorticoids, including oral or parenteral prednisone or equivalent (at least 2 mg/kg per day or at least 20 mg total dose) for more than 2 weeks in the past 6 months or high-dose inhaled steroids (more than 800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months. Nasal and topical steroids are allowed.
Has received immunoglobulin or other blood products within the 3 months prior to study entry
History of Guillain-Barre syndrome in the subject or subject's family, including parents, siblings, half-siblings, and children
Onset of a neurological disorder including (but not limited to) absent ankle and patellar deep tendon reflexes 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 within the past 6 months
Has any condition that would, in the opinion of the site investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol

Exclusion Criteria for Step II:

Has received a nonlicensed agent (vaccine, drug, biologic, device, blood product, or medication), other than from participation in this study, since Dose #1 or expects to receive another nonlicensed agent before the end of the study
Use of anti-cancer chemotherapy or radiation therapy since 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 steroids (at least 2 mg/kg per day or at least 20 mg total dose) for more than 2 weeks since vaccine Dose #1 or high-dose inhaled steroids (more than 800 mcg/day of beclomethasone dipropionate or equivalent) since Dose #1 (nasal and topical steroids are allowed)
Has received immunoglobulin or other blood products since 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 study vaccine
Any Grade 4 injection site reactions or fever experienced by a participant, 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
New occurrence or new awareness of Guillain-Barre syndrome in the participant or participant's family (parents, siblings, half-siblings, or children) since Dose #1
New onset of a neurological disorder including (but not limited to) absent ankle and patellar deep tendon reflexes in both legs (all four absent) since Dose #1
Disproportionate loss of strength in lower extremity or extremities compared to the upper extremities (not thought to be related to pregnancy) since Dose #1
Documented infection with 2009 Influenza A (H1N1) since Dose #1
Refusal of further vaccination by participant, parent, or guardian
Development of any new disease that the investigator judges to be clinically significant or clinically significant findings since Dose #1 that, in the investigator's opinion, would compromise the safety of the subject
Withdrawal of consent. Consent may be withdrawn at any time and for any reason, without penalty.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00992836

Show 42 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:

Pat Flynn, MD

St. Jude Children's Research Hospital

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.

Gelinck LB, van den Bemt BJ, Marijt WA, van der Bijl AE, Visser LG, Cats HA, Rimmelzwaan GF, Kroon FP. Intradermal influenza vaccination in immunocompromized patients is immunogenic and feasible. Vaccine. 2009 Apr 21;27(18):2469-74. Epub 2009 Feb 24.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	IMPAACT P1088, 10840
Study First Received:	October 8, 2009
Last Updated:	November 18, 2009
ClinicalTrials.gov Identifier:	NCT00992836 History of Changes
Health Authority:	United States: Food and Drug Administration

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

Influenza A Virus, H1N1 Subtype
Vaccine
Children
Adolescents

HIV-Infected
Perinatal HIV Infection
Treatment experienced

Additional relevant MeSH terms:

Communicable Diseases
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