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

NCT00992836 | Completed Phase 2 Results DMC

• 3 other identifiers: P108810840IMPAACT P1088
• Study Type: interventional
• Target: 155
• Locations: 2 countries
• Sites: 37

Brief Summary

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

Conditions

HIV Infections; H1N1 Influenza Virus

Keywords

Influenza A Virus, H1N1 Subtype; Vaccine; Children; Adolescents; HIV-Infected; Perinatal HIV Infection; Treatment experienced

Outcome Measures

Primary Outcomes (4)

• The Number of Participants Who Had at Least One Adverse Event (AE)

  Shows the number of participants who had at least one adverse event (AE) in each category. The AEs 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.

  Measured up to 7 months after vaccination

• The Number of Participants Who Had at Least One AE Attributed to the Study Vaccine

  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.

  Measured up to 7 months after vaccination

• Withholding of Second Vaccine Dose Due to Adverse Reactions Attributed to First Dose

  Measured at Day 21

• Percent of Participants With a Hemagglutinin Inhibition (HAI) Titer of >=40

  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.

  Measured at 21 days after first dose and 10 days after second dose

Secondary Outcomes (5)

• Percent of Participants With an HAI Titer >=40 at Long-term Follow-up

  Measured at 6 months after second dose

• Geometric Mean Antibody Titers (GMT) HAI

  Measured after first and second doses and 6 months after second dose

• Cell-mediated Immune Responses, Measured by B-cell and T-cell Enzyme-linked Immunosorbent Spot (ELISPOT) Assay Values

  Measured at entry, 21 days after first dose, and 10 days after second dose

• HAI Titers Against Seasonal Influenza Viruses Containing Trivalent Influenza Vaccine (TIV)

  Measured at entry, 21 days after first dose, and 10 days and 6 months after second dose

• Cell-mediated Immune Responses to Influenza Viruses Contained in TIV and Other Antigens

  Measured at entry, 21 days after first dose, and 10 days after second dose

Study Arms (1)

Influenza A (H1N1) 2009 monovalent vaccine

EXPERIMENTAL

All participants received two doses of the H1N1 influenza virus vaccine, administered 21 days apart.

Biological: Influenza A (H1N1) 2009 monovalent vaccine

Interventions

Influenza A (H1N1) 2009 monovalent vaccine BIOLOGICAL

Two doses of vaccine, delivered 21 days apart, with each dose consisting of two 15-microgram intramuscular injections

Influenza A (H1N1) 2009 monovalent vaccine

Eligibility Criteria

• Age: 4 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (37)

UAB Pediatric Infectious Diseases CRS

Birmingham, Alabama, 35233, United States

Location

Usc La Nichd Crs

Alhambra, California, 91803, United States

Location

University of California, UC San Diego CRS

La Jolla, California, 92093-0672, United States

Location

Miller Children's Hosp. Long Beach CA NICHD CRS

Long Beach, California, 90806, United States

Location

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

Los Angeles, California, 90095-1752, United States

Location

Univ. of California San Francisco NICHD CRS

San Francisco, California, 94143, United States

Location

Harbor UCLA Medical Ctr. NICHD CRS

Torrance, California, 90502, United States

Location

Univ. of Colorado Denver NICHD CRS

Aurora, Colorado, 80045, United States

Location

Children's National Med. Ctr. Washington DC NICHD CRS

Washington D.C., District of Columbia, 20010, United States

Location

Howard Univ. Washington DC NICHD CRS

Washington D.C., District of Columbia, 20060, United States

Location

South Florida CDTC Ft Lauderdale NICHD CRS

Fort Lauderdale, Florida, 33316, United States

Location

Univ. of Florida Jacksonville NICHD CRS

Jacksonville, Florida, 32209, United States

Location

Pediatric Perinatal HIV Clinical Trials Unit CRS

Miami, Florida, 33136, United States

Location

USF - Tampa NICHD CRS

Tampa, Florida, 33606, United States

Location

Rush Univ. Cook County Hosp. Chicago NICHD CRS

Chicago, Illinois, 60612, United States

Location

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

Chicago, Illinois, 60614-3393, United States

Location

Univ. of Maryland Baltimore NICHD CRS

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Univ. Baltimore NICHD CRS

Baltimore, Maryland, 21287, United States

Location

Children's Hosp. of Boston NICHD CRS

Boston, Massachusetts, 02115, United States

Location

Boston Medical Center Ped. HIV Program NICHD CRS

Boston, Massachusetts, 02118, United States

Location

WNE Maternal Pediatric Adolescent AIDS CRS

Worcester, Massachusetts, 01605, United States

Location

Children's Hospital of Michigan NICHD CRS

Detroit, Michigan, 48201, United States

Location

Rutgers - New Jersey Medical School CRS

Newark, New Jersey, 01703, United States

Location

Nyu Ny Nichd Crs

New York, New York, 10016, United States

Location

Metropolitan Hosp. NICHD CRS

New York, New York, 10029, United States

Location

Columbia IMPAACT CRS

New York, New York, 10032, United States

Location

Strong Memorial Hospital Rochester NY NICHD CRS

Rochester, New York, 14642, United States

Location

SUNY Stony Brook NICHD CRS

Stony Brook, New York, 11794-8111, United States

Location

Bronx-Lebanon CRS

The Bronx, New York, 10457, United States

Location

Jacobi Med. Ctr. Bronx NICHD CRS

The Bronx, New York, 10461, United States

Location

DUMC Ped. CRS

Durham, North Carolina, 27710, United States

Location

The Children's Hosp. of Philadelphia IMPAACT CRS

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude Children's Research Hospital CRS

Memphis, Tennessee, 38105-3678, United States

Location

Texas Children's Hospital CRS

Houston, Texas, 77030-2399, United States

Location

Seattle Children's Research Institute CRS

Seattle, Washington, 98101, United States

Location

University of Puerto Rico Pediatric HIV/AIDS Research Program CRS

San Juan, 00935, Puerto Rico

Location

San Juan City Hosp. PR NICHD CRS

San Juan, 00936, Puerto Rico

Location

Related Publications (6)

• 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.

  PMID: 19423869 BACKGROUND

• 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. doi: 10.1016/j.vaccine.2009.02.053. Epub 2009 Feb 24.

  PMID: 19368788 BACKGROUND

• Flynn P, Nachman S, Spector SA, Cunningham CK, Weinberg A, Pass R, Muresan P, Levy W, Siberry G, Handelsman E for the IMPAACT P1088 and P1089 Teams: Safety and Immunogenicity of 2009 H1N1 Influenza Immunization in HIV-1 Perinatally Infected Children and Youth. Presented at the IDSA conference, October 2010.

  RESULT

• Flynn PM, Nachman S, Spector SA, Cunningham CK, Weinberg A, Pass R, Muresan P, Levy W, Petzold E, Heckman B, Siberry G, Handelsman E for the IMPAACT P1088 and P1089 Teams. 2009 Influenza A (H1N1) Immunization in HIV-1 Perinatally Infected Children and Youth. Presented at the Retroviruses Conference, Feb 2010.

  RESULT

• Curtis DJ, Muresan P, Nachman S, Fenton T, Richardson KM, Dominguez T, Flynn PM, Spector SA, Cunningham CK, Bloom A, Weinberg A. Characterization of functional antibody and memory B-cell responses to pH1N1 monovalent vaccine in HIV-infected children and youth. PLoS One. 2015 Mar 18;10(3):e0118567. doi: 10.1371/journal.pone.0118567. eCollection 2015.

  PMID: 25785995 DERIVED

• Flynn PM, Nachman S, Muresan P, Fenton T, Spector SA, Cunningham CK, Pass R, Yogev R, Burchett S, Heckman B, Bloom A, Utech LJ, Anthony P, Petzold E, Levy W, Siberry GK, Ebiasah R, Miller J, Handelsman E, Weinberg A; IMPAACT P1088 Team. Safety and immunogenicity of 2009 pandemic H1N1 influenza vaccination in perinatally HIV-1-infected children, adolescents, and young adults. J Infect Dis. 2012 Aug 1;206(3):421-30. doi: 10.1093/infdis/jis360. Epub 2012 May 21.

  PMID: 22615311 DERIVED

Related Links

• Click here for information on the IMPAACT group and for the package insert on the H1N1 vaccine.
• Click here for the table used for grading toxicities: DAIDS Grading Severity of AEs, V1.0, Dec04.

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Melissa Allen, Director, IMPAACT Operations Center
• Organization: Family Health International (FHI 360)

mallen@fhi360.org

919-405-1429

Study Officials

• Pat Flynn, MD

  St. Jude Children's Research Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2009
• First Posted: October 9, 2009
• Study Start: October 1, 2009
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: November 5, 2021
• Results First Posted: February 9, 2012

Record last verified: 2014-12

Locations

US (35); PR (2)