Clinical Trial to Compare the Immunogenicity, Safety, and Tolerability of an Adjuvanted A(H1N1) Influenza Vaccine Versus Non-Adjuvanted A(H1N1) Influenza Vaccines in Patients With HIV-1 Infection

Official Title: “A Phase III, Randomized, Controlled, Open Label Study to Evaluate the Immunogenicity, Safety, and Tolerability of an Adjuvanted A(H1N1) Vaccine Versus Non-Adjuvanted Vaccines Against Novel H1N1 Virus in Patients With Human Immunodeficiency Virus Type 1 (HIV-1) Infection”

This is a phase III, randomized, controlled, open label study with two vaccine regimens. The study will assess the relative safety and immunogenicity of vaccine regimens comparing adjuvanted versus non-adjuvanted formulations of A(H1N1) inactivated influenza virus vaccine in subjects with Human Immunodeficiency Virus Type 1 (HIV-1) Infection and to compare safety and immunogenicity data with a contemporaneously enrolled control group of age-comparable, healthy subjects.

Because certain individuals may be hypo-responsive to influenza vaccination, additional studies with high-risk groups are warranted in order to determine the optimal vaccine formulation and dosing schedule for prevention of novel H1N1 virus infection.

Intervention(s) in this Clinical Trial

• Biological: adjuvanted A(H1N1) influenza vaccine
  • 7.5 ug of HA antigen; adjuvanted; monovalent
• Biological: non-adjuvanted A(H1N1) influenza vaccine
  • 15 ug of HA antigen; non-adjuvanted; trivalent
• Biological: non-adjuvanted A(H1N1) influenza vaccine
  • 15 mcg of antigen; non-adjuvanted; trivalent

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Group A: High Risk Subjects
  • Each subject will receive two doses of the assigned vaccine, the first on Study Day 1, and the second on Study Day 22
• Experimental: Group B: High Risk Subjects
  • Each subject will receive two doses of the assigned vaccine, the first on Study Day 1, and the second on Study Day 22
• Experimental: Group C: Healthy Subjects
  • Each subject will receive two doses of the assigned vaccine, the first on Study Day 1, and the second on Study Day 22
• Experimental: Group D: Healthy Subjects
  • Each subject will receive two doses of the assigned vaccine, the first on Study Day 1, and the second on Study Day 22

Primary Measures

• The primary objective of this study is to determine the optimal influenza vaccination strategy in patients with HIV infection
  • Time Frame: 3 months
    Safety Issue?: No

Secondary Measures

• Assess whether the adjuvanted vaccine offers a meaningful benefit in relation to the non-adjuvanted vaccine in this at-risk population
  • Time Frame: 3 months
    Safety Issue?: No
• Assess whether two doses of either study vaccine will provide meaningful benefit in comparison to one dose
  • Time Frame: 3 months
    Safety Issue?: No
• Assess the persistence of antibody levels in the two vaccine groups
  • Time Frame: 3 months
    Safety Issue?: No
• Gain further insight into the safety of the adjuvanted and non-adjuvanted H1N1 vaccines in this high-risk patient population
  • Time Frame: 3 months
    Safety Issue?: Yes

Inclusion Criteria:

For HIV-1 Infected Subjects:

• Adults between 18-60 years old (inclusive)
• Any sex or ethnicity
• Confirmed Diagnosis of HIV-1 infection
• CD4+ cells count >200 per mm3 within 3 months prior to inclusion in the study
• HIV-1 viral load below 200 copies/mL within 60 days prior to inclusion in the study
• Childbearing potential women must be willing to use an acceptable contraceptive method. Acceptable contraceptive methods are defined as one or more of the following:
• 1. Hormone contraceptive (such as oral, injectable, transdermal patch, subcutaneous implant, cervical ring)
• 2. Barrier (condom with spermicide or diaphragm with spermicide) at each intercourse and during the whole intercourse
• 3. Intra-uterine device (IUD)
• 4. Monogamous relation with vasectomized partner (must have been vasectomized at least six months before the volunteer entered the study)
• No changes in the HAART antiviral therapy for the previous 4 weeks and/or change in the predicted antiviral therapy through study Day 43 (3 weeks after the second dose of the vaccine)
• No use of immunomodulatory therapy, including cyclosporine, products containing IgG, interleukins, interferons, or systemic glucocorticoids (including inhalatory) within 3 months before study inclusion
• Subjects capable of respecting all the study procedures and available for all visits scheduled to the investigation site
• Subjects capable of understanding the nature and risk of the study proposed and signing the consent form
• The subjects may have other underlying diseases, such as, but not limited to, hypertension, diabetes, cardiac ischemic disease, or hypothyroidism, however their symptoms/signs must be currently under control with medical treatment according to the investigator's evaluation

For Healthy Adults:

• Adults between 18-60 years old (inclusive)
• Any sex and ethnicity
• Subjects with good health as determined by medical history, physical evaluation, and investigator's clinical opinion
• Childbearing potential women must be willing to use an acceptable contraceptive method. Acceptable contraceptive methods are defined as one or more of the following:
• 1. Hormone contraceptive (such as oral, injectable, transdermal patch, subcutaneous implant, cervical ring).
• 2. Barrier (condom with spermicide or diaphragm with spermicide) at each intercourse and during the whole sexual intercourse
• 3. Intra-uterine device (IUD)
• 4. Monogamous relation with vasectomized partner (must have been vasectomized for at least six months before the volunteer entered the study)
• Subjects capable of respecting all the study procedures and available for all the visits scheduled at the investigation site
• Subjects capable of understanding the nature and risk of the study proposed and signing the consent form
• There will be NO blood sample collection of healthy volunteers viewing the determination of their serological status regarding the HIV virus.

Exclusion Criteria:

For HIV-1-Infected Subjects:

• HIV-1 viral load above 500 copies/mL within 6 months prior to inclusion in the study
• Previous laboratory confirmed diagnosis of an infection by the novel H1N1 virus
• Receipt of another vaccine against the novel H1N1 virus within 3 months prior to inclusion in the study
• Any recent vaccine given within the last 21 days (inclusive)
• History of allergic reaction to an influenza vaccine in the past, or a current or previous occurrence of allergy to egg or egg protein, kanamycin, and neomycin sulfate
• Acute febrile disease (vaccination may be delayed up to 3 days after the resolution of the symptoms)
• History of cancer, except for skin cancer, including Kaposi's Sarcoma, basal cell carcinoma, and non-invasive malignancy related to HPV
• History of cognitive disorders
• History of progressive or severe neurological disorders, including Guillain-Barré
• Syndrome
• Pregnancy or breast-feeding
• Use of immunomodulatory therapy, including cyclosporin, products containing IgG, interleukins, and interferons, within 3 months prior to inclusion in the study
• Receipt of parenteral immunoglobulin, hemotherapy, and/or plasma derivatives within 3 months prior to inclusion in the study
• Projected life expectancy lower than 12 months
• Receipt of any investigational product within 12 months prior to inclusion in the study

For Healthy Adults:

• Previous laboratory confirmed diagnosis of an infection by the novel H1N1 virus
• Receipt of another vaccine against the novel H1N1 virus within 3 months prior to inclusion in the study
• Any recent vaccine given within the last 21 days (inclusive)
• History of allergic reaction to influenza vaccine in the past, or a current or previous allergy to egg or egg protein, kanamycin, and neomycin sulfate
• Acute febrile disease (the vaccination may be delayed up to 3 days after symptoms resolution)
• Pregnancy or breast-feeding
• Receipt of parenteral immunoglobulin, hemotherapy, and/or plasma derivatives within 3 months prior to inclusion in the study
• Receipt of any investigational product within 12 months prior to inclusion in the study

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: Chiltern Pesquisa Clinica Ltda Industry

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01032408

Study ID Number: V111_14TP

ClinicalTrials.gov Identifier: NCT01032408

Health Authority: Brazil: National Health Surveillance Agency