Clinical trial NCT00992433: H1N1 Vaccine at Two Dose Levels in HIV Positive Adults
Official title: A Phase II Study in HIV-seropositive Adults to Assess the Safety and Immunogenicity of an Unadjuvanted Novartis H1N1 Influenza Vaccine Administered at Two Dose Levels
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza
Keywords: influenza, H1N1, vaccine, human immunodeficiency virus
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2009-10-09
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to see how the body reacts to different strengths of the H1N1 flu shot in persons infected with human immunodeficiency virus (HIV). This study will also compare how the CD4 count (cells that help fight disease) affects the body's response to the H1N1 flu shot. In this study, 2 strengths of the H1N1 flu shot will be given twice, about 3 weeks apart. The results of this study will help researchers find out if the different strengths of the H1N1 flu shot make the body produce H1N1 antibodies that are better at fighting H1N1 flu. About 240 HIV positive subjects, ages 18-64 years, will be asked to take part in this study. Study procedures include: blood sampling, physical exams, and use of memory aids to record temperature, medications and symptoms. The length of patient participation is about 7 months.

Detailed description: Recently, a novel swine-origin influenza A/H1N1 virus was identified as a significant cause of febrile respiratory illnesses in Mexico and the United States. It rapidly spread to many countries around the world, prompting the World Health Organization (WHO) to declare a pandemic on June 11, 2009. The immunosuppression associated with human immunodeficiency virus (HIV)-infection has been related to diminished immune responses to vaccination against multiple pathogens, including influenza. The widespread use of antiretroviral therapy has resulted in a significant decrease in the mortality from HIV/acquired immune deficiency syndrome (AIDS) and, as a result, HIV-infected subjects constitute a demographically growing subpopulation in the United States. Currently, novel H1N1 vaccines are being evaluated in the general population. Researchers propose to evaluate the safety and immunogenicity of the novel H1N1 vaccines in HIV-infected subjects, because the data from clinical trials enrolling healthy subjects may not apply to immunosuppressed individuals; and an evaluation of the immune responses to vaccination against new, pandemic influenza viruses has never been performed in HIV-infected subjects. This is a randomized, open label, Phase II study in HIV seropositive males and non-pregnant females, aged 18-64 years. This study is designed to investigate the safety, reactogenicity, and immunogenicity of an inactivated influenza H1N1 virus vaccine at 2 dose levels. Subjects will be randomized into 2 dose groups, stratified by cluster of differentiation (CD4) cell count at enrollment (120 subjects per dose group with 60 subjects per CD4 cell count stratum, \<200/mL or greater than or equal to 200/mL) to receive intramuscular (IM) inactivated influenza H1N1 vaccine at 15 mcg (Group 1) or 30 mcg (Group 2). The H1N1 vaccine will be administered at Day 0 and Day 21. Following immunization, safety will be measured by assessment of adverse events through 21 days following the last vaccination (Day 42 for those receiving both doses and Day 21 for those who do not receive the second dose), serious adverse events and new-onset chronic medical conditions through 7 months post first vaccination (Day 201), and reactogenicity to the vaccine for 8 days following each vaccination (Day 0-7). A CD4/CD8 panel and viral load will be measured prior to first vaccination on Day 0 and at Day 10 post the second vaccination. Immunogenicity testing will include hemagglutination inhibition assay (HAI) and neutralizing antibody testing on serum obtained on the day of each vaccination (prior to vaccination), on Day 10 after each vaccination, 21 days following the second vaccination (Day 42) and 6 months after the second vaccination (Day 201). The primary objectives of this study are: (safety), to assess the safety of the unadjuvanted, inactivated H1N1 vaccine in HIV-1 seropositive adults when administered at the 15 mcg or 30 mcg dose and (immunogenicity) to assess the antibody response following 1 and 2 doses of inactivated H1N1 vaccine administered intramuscularly at the 15 mcg or 30 mcg dose levels in HIV-1 seropositive adults stratified by CD4 count at enrollment.

Eligibility criteria: Inclusion Criteria:

* Human immunodeficiency virus (HIV) infection defined as documented by an enzyme-linked immunosorbent assay (ELISA) and confirmed with a Western blot at any time prior to study entry. Serum HIV-1 antigen, plasma HIV-1 ribonucleic acid (RNA), or any Food and Drug Administration (FDA) approved antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
* Males or non-pregnant females age 18-64, inclusive.
* Women of child-bearing potential (not surgically sterile via tubal ligation, bilateral oophorectomy or hysterectomy or who are not postmenopausal for greater than or equal to 1 year) must agree to practice adequate contraception that may include, but is not limited to, abstinence, monogamous relationship with vasectomized partner, barrier methods such as condoms, diaphragms, spermicides, intrauterine devices, Depo-Provera injections or Implanon implants for at least 30 days following the last vaccination.
* Are medically stable, as determined by the Investigator (based on review of health status, vital signs, medical history, and targeted physical examination. Vital signs must be within normal ranges prior to the first vaccination (heart rate 55-100, blood pressure systolic \<160, blood pressure diastolic \<90).
* Receipt of the 2009-2010 seasonal influenza vaccine at least two weeks prior to enrollment in this study.
* Intend to be available for follow-up visits and phone call access through 7 months following receipt of H1N1 vaccine.
* Are able to understand and comply with planned study procedures.
* Subject receiving regular medical follow-up care for HIV.
* Has a documented platelet count of \>50,000mm\^3 and an absolute neutrophil count (ANC) of \>500mm\^3 within the 3 months prior to study entry.
* Provide written informed consent prior to initiation of any study procedures.

Exclusion Criteria:

* Treatment for an opportunistic infection (OI) initiated within 2 weeks prior to enrollment, or have symptoms that have not stabilized.
* Have a known allergy to eggs or other components of the vaccine (including polymyxin, neomycin, and chicken protein).
* Women who are pregnant or breastfeeding.
* Have a positive urine or serum pregnancy test within 24 hours prior to vaccination.
* Use of anticancer chemotherapy or radiation therapy (cytotoxic) within the preceding 36 months.
* Have a neoplastic disease that will be treated with chemotherapy or radiation, or a history of any hematologic malignancy.
* Have long term use of glucocorticoids including oral, parenteral or high-dose inhaled steroids. For oral or parenteral: prednisone or equivalent (greater than or equal to 2.0 mg/kg per day or greater than or equal to 20 mg total dose) for more than 2 consecutive weeks (or 2 weeks total) in the past 3 months. For inhaled steroids: \>800 mcg/day of beclomethasone dipropionate or equivalent within the preceding 6 months. (Nasal and topical steroids are allowed.)
* Have an uncontrolled major psychiatric diagnosis.
* Have a history of receiving immunoglobulin or other blood products within the 3 months prior to vaccination in this study.
* Received an experimental agent (vaccine, drug, biologic, device, or medication) within 1 month prior to vaccination in this study or expect to receive an experimental agent during this study (prior to the Day 201 follow-up call).
* Have received any live licensed vaccines within 4 weeks or inactivated licensed vaccines within 2 weeks prior to vaccination in this study or plan receipt of such vaccines within 21 days following the second vaccination.
* Have an acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe, or would interfere with the evaluation of responses.
* Have a history of severe reactions following previous immunization with influenza virus vaccines.
* Have a moderate-severe acute illness, including an oral temperature greater than 100.4 degrees Fahrenheit, within 72 hours prior to vaccination. (This may result in a temporary delay of vaccination).
* Have any condition that would, in the opinion of the site investigator, place them at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
* Participated in a novel influenza 2009 H1N1 influenza vaccine study or have history of novel 2009 H1N1 influenza infection prior to enrollment.
* Have a history of alcohol or drug abuse in the last 3 months.
* Plan to travel outside of North America at any time between the first vaccination and 42 days following the first vaccination.
* Have a history of Guillain-Barré Syndrome.
* Have any condition that the investigator believes may interfere with successful completion of the study.

Primary outcomes:
measure: Number of Participants in the CD4 Less Than 200/mL Stratum With 4-Fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 10 Days Following the First Dose of H1N1 Vaccine
timeFrame: Day 0 prior to vaccination and 10 days after the first vaccination
measure: Number of Participants in the CD4 Less Than 200/mL Stratum With 4-Fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 21 Days Following the First Dose of H1N1 Vaccine
timeFrame: Day 0 prior to vaccination and 21 days after the first vaccination
measure: Number of Participants in the CD4 Less Than 200/mL Stratum With 4-Fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 10 Days Following the Second Dose of H1N1 Vaccine
timeFrame: Day 0 prior to vaccination and 10 days after the second vaccination
measure: Number of Participants in the CD4 Less Than 200/mL Stratum With 4-Fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 21 Days Following the Second Dose of H1N1 Vaccine
timeFrame: Day 0 prior to vaccination and 21 days after the second vaccination
measure: Number of Participants in the CD4 Less Than 200/mL Stratum With 4-Fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 180 Days Following the Second Dose of H1N1 Vaccine
timeFrame: Day 0 prior to vaccination and 180 days after the second vaccination
measure: Number of Participants in the CD4 200/mL or Greater Stratum With 4-Fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 10 Days Following the First Dose of H1N1 Vaccine
timeFrame: Day 0 prior to vaccination and 10 days after the first vaccination
measure: Number of Participants in the CD4 CD4 200/mL or Greater Stratum With 4-Fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 21 Days Following the First Dose of H1N1 Vaccine
timeFrame: Day 0 prior to vaccination and 21 days after the first vaccination
measure: Number of Participants in the CD4 200/mL or Greater Stratum With 4-Fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 10 Days Following the Second Dose of H1N1 Vaccine
timeFrame: Day 0 prior to vaccination and 10 days after the second vaccination
measure: Number of Participants in the CD4 200/mL or Greater Stratum With 4-Fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 21 Days Following the Second Dose of H1N1 Vaccine
timeFrame: Day 0 prior to vaccination and 21 days after the second vaccination
measure: Number of Participants in the CD4 200/mL or Greater Stratum With 4-Fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 180 Days Following the Second Dose of H1N1 Vaccine
timeFrame: Day 0 prior to vaccination and 180 days after the second vaccination
measure: Number of Participants in the CD4 Less Than 200/mL Stratum With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus at Baseline and 10 Days Following the First Dose of H1N1 Vaccine
timeFrame: Day 0 prior to vaccination and 10 days after the first vaccination
measure: Number of Participants in the CD4 Less Than 200/mL Stratum With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 21 Days Following the First Dose of H1N1 Vaccine
timeFrame: Day 21 after the first vaccination
measure: Number of Participants in the CD4 Less Than 200/mL Stratum With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 10 Days Following the Second Dose of H1N1 Vaccine
timeFrame: Day 10 after the second vaccination
measure: Number of Participants in the CD4 Less Than 200/mL Stratum With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 21 Days Following the Second Dose of H1N1 Vaccine
timeFrame: Day 21 after the second vaccination
measure: Number of Participants in the CD4 Less Than 200/mL Stratum With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 180 Days Following the Second Dose of H1N1 Vaccine
timeFrame: Day 180 after the second vaccination
measure: Number of Participants in the CD4 200/mL or Greater Stratum With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus at Baseline Prior to the First Dose of H1N1 Vaccine
timeFrame: Day 0 prior to the first vaccination
measure: Number of Participants in the CD4 200/mL or Greater Stratum With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 10 Days Following the First Dose of H1N1 Vaccine
timeFrame: Day 10 after the first vaccination
measure: Number of Participants in the CD4 200/mL or Greater Stratum With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 21 Days Following the First Dose of H1N1 Vaccine
timeFrame: Day 21 after the first vaccination
measure: Number of Participants in the CD4 200/mL or Greater Stratum With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 10 and 21 Days Following the Second Dose of H1N1 Vaccine
timeFrame: Day 10 and Day 21 after the second vaccination
measure: Number of Participants in the CD4 200/mL or Greater Stratum With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 180 Days Following the Second Dose of H1N1 Vaccine
timeFrame: Day 180 after the second vaccination
measure: Number of Participants Reporting Solicited Subjective Systemic Reactions After the First Vaccination
timeFrame: Within 8 days post first vaccination (Day 0-7).
measure: Number of Participants Reporting Solicited Subjective Systemic Reactions After the Second Vaccination
timeFrame: Within 8 days post second vaccination (Day 0-7).
measure: Number of Participants Reporting Fever After the First Vaccination
timeFrame: Within 8 days post first vaccination (Day 0-7).
measure: Number of Participants Reporting Fever After the Second Vaccination
timeFrame: Within 8 days post second vaccination (Day 0-7).
measure: Number of Participants Reporting Solicited Subjective Local Reactions After the First Vaccination
timeFrame: Within 8 days post first vaccination (Day 0-7).
measure: Number of Participants Reporting Solicited Subjective Local Reactions After the Second Vaccination
timeFrame: Within 8 days post second vaccination (Day 0-7).
measure: Number of Participants Reporting Solicited Quantitative Local Reactions After the First Vaccination
timeFrame: Within 8 days post first vaccination (Day 0-7).
measure: Number of Participants Reporting Solicited Quantitative Local Reactions After the Second Vaccination
timeFrame: Within 8 days post second vaccination (Day 0-7).
measure: Number of Participants Reporting Vaccine-Associated Serious Adverse Events (SAEs)
timeFrame: Day 0 through Day 180 after the last vaccination
Secondary outcomes:
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland Baltimore - Institute of Human Virology
state: Maryland
city: St. Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
References:
citation: El Sahly HM, Davis C, Kotloff K, Meier J, Winokur PL, Wald A, Johnston C, George SL, Brady RC, Lehmann C, Stokes-Riner A, Keitel WA. Higher antigen content improves the immune response to 2009 H1N1 influenza vaccine in HIV-infected adults: a randomized clinical trial. J Infect Dis. 2012 Mar 1;205(5):703-12. doi: 10.1093/infdis/jir837. Epub 2012 Jan 24.