Clinical trial NCT01032408: Immunogenicity, Safety, and Tolerability of MF59-Adjuvanted Versus Non-Adjuvanted Influenza Vaccines in Patients With HIV-1 Infection
Official title: A Phase 3, Randomized, Controlled, Open Label Study to Evaluate the Immunogenicity, Safety, and Tolerability of MF59-Adjuvanted Versus Non-Adjuvanted Vaccines Against Novel H1N1 Virus in Patients With Human Immunodeficiency Virus Type 1 (HIV-1) Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: H1N1 Influenza Virus
Human Immunodeficiency Virus Type 1 (HIV-1) Infection
Keywords: Influenza A Virus
Virus Diseases
Influenza, Human
HIV-1
Immunodeficiency Virus
H1N1
HIV Infection
Immunogenicity
safety
tolerability
Lead sponsor: Chiltern Pesquisa Clinica Ltda
Sponsor class: INDUSTRY
First posted: 2009-12-15
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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 90 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 antiviral therapy (including HAART) 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, 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, 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

Primary outcomes:
measure: Geometric Mean HI Titer by Visit
timeFrame: 13 months after vaccination (Day 1, Day 22, Day 43, Day 133, Day 223 and Day 403)
measure: Percentage of Subjects Who Reached Seroprotection by Visit
timeFrame: 13 Months after vaccination (Day 22, Day 43, Day 133, Day 223 and Day 403)
measure: Difference in the Seroconversion Rates or Significant Increase by Visit (Vaccine With Adjuvant - Vaccine Without Adjuvant)
timeFrame: 13 Months after vaccination (Day 22, Day 43, Day 133, Day 223 and Day 403)
Secondary outcomes:
measure: Geometric Mean Ratio by Visit
timeFrame: 13 months after vaccination (Day 22/Day1, Day 43/Day 1, Day 43/Day 22, Day 133/Day 43, Day 223/Day 43 and Day 403/Day 223)
measure: Ratio of Immunogenicity Data by Visit (Vaccine with Adjuvant:Vaccine Without Adjuvant)
timeFrame: 13 months after vaccination (Day 1, Day 22, Day 22/Day1, Day 43, Day 43/Day 1, Day 43/Day 22, Day 133, Day 133/Day 43, Day 223, Day 223/Day 43 and Day 403, Day 403/Day 223)
measure: Percentage of Subjects Who Seroconverted or Had a Significant Increase in GMT by Visit
timeFrame: 13 Months after vaccination (Day 22, Day 43, Day 133, Day 223 and Day 403)
measure: Difference in Seroprotection Rates by Visit (Vaccine with Adjuvant - Vaccine without Adjuvant)
timeFrame: 13 months after vaccination (Day 22, Day 43, Day 133, Day 223, Day 403)
Other outcomes:
Locations:
city: Curitiba
country: Brazil
facility: Centro Médico São Francisco
state: PR
city: São Paulo
country: Brazil
facility: ICG - Instituto Centro de Genomas
state: SP
Study officials:
References:
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citation: Sullivan PS, Hanson DL, Dworkin MS, Jones JL, Ward JW; Adult and Adolescent Spectrum of HIV Disease Investigators. Effect of influenza vaccination on disease progression among HIV-infected persons. AIDS. 2000 Dec 1;14(17):2781-5. doi: 10.1097/00002030-200012010-00018.
citation: Tasker SA, Treanor JJ, Paxton WB, Wallace MR. Efficacy of influenza vaccination in HIV-infected persons. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1999 Sep 21;131(6):430-3. doi: 10.7326/0003-4819-131-6-199909210-00006.
citation: Yamanaka H, Teruya K, Tanaka M, Kikuchi Y, Takahashi T, Kimura S, Oka S; HIV/Influenza Vaccine Study Team. Efficacy and immunologic responses to influenza vaccine in HIV-1-infected patients. J Acquir Immune Defic Syndr. 2005 Jun 1;39(2):167-73.