Immunogenicity, Safety, and Tolerability of MF59-Adjuvanted Versus Non-Adjuvanted Influenza Vaccines in Patients With HIV-1 Infection

NCT01032408 | Completed Phase 3

• 1 other identifier: V111_14TP
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (3)

• Geometric Mean HI Titer by Visit

  Geometric mean hemagglutination inhibition (HI) titer = GMT

  13 months after vaccination (Day 1, Day 22, Day 43, Day 133, Day 223 and Day 403)

• Percentage of Subjects Who Reached Seroprotection by Visit

  The primary objective of this study is to determine the optimal influenza vaccination strategy in patients with HIV infection. The percentage of subjects that reached seroprotection in comparison to the pre-vaccination result are presented by visit. Seroprotection was defined as HI titer ≥40.

  13 Months after vaccination (Day 22, Day 43, Day 133, Day 223 and Day 403)

• Difference in the Seroconversion Rates or Significant Increase by Visit (Vaccine With Adjuvant - Vaccine Without Adjuvant)

  The primary objective of this study was to help determine the ideal strategy of vaccination against pandemic H1N1 influenza in subjects with invasive solid tumors/hematologic neoplasms. Comparisons were made by vaccine group using differences in the percentage of subjects with seroconversion/significant increase and were presented with 95% confidence intervals.

  13 Months after vaccination (Day 22, Day 43, Day 133, Day 223 and Day 403)

Secondary Outcomes (4)

• Geometric Mean Ratio by Visit

  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)

• Ratio of Immunogenicity Data by Visit (Vaccine with Adjuvant:Vaccine Without Adjuvant)

  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)

• Percentage of Subjects Who Seroconverted or Had a Significant Increase in GMT by Visit

  13 Months after vaccination (Day 22, Day 43, Day 133, Day 223 and Day 403)

• Difference in Seroprotection Rates by Visit (Vaccine with Adjuvant - Vaccine without Adjuvant)

  13 months after vaccination (Day 22, Day 43, Day 133, Day 223, Day 403)

Study Arms (4)

HIV-1 Infected Subjects Receiving Vaccine with Adjuvant

EXPERIMENTAL

Each subject received two doses of vaccine with adjuvant (Focetria®), the first on Study Day 1, and the second on Study Day 22

Biological: Focetria®

HIV-1 Infected Subjects Receiving Vaccine without Adjuvant

EXPERIMENTAL

Each subject received two doses of vaccine without adjuvant (Begrivac®), the first on Study Day 1, and the second on Study Day 22

Biological: Begrivac®

Healthy Subjects Receiving Vaccine with Adjuvant

EXPERIMENTAL

Each subject received two doses of vaccine with adjuvant (Focetria®), the first on Study Day 1, and the second on Study Day 22

Biological: Focetria®

Healthy Subjects Receiving Vaccine without Adjuvant

EXPERIMENTAL

Each subject received two doses of vaccine without adjuvant (Begrivac®), the first on Study Day 1, and the second on Study Day 22

Biological: Begrivac®

Interventions

Focetria® BIOLOGICAL

7.5 ug of HA antigen; adjuvanted; monovalent

HIV-1 Infected Subjects Receiving Vaccine with Adjuvant; Healthy Subjects Receiving Vaccine with Adjuvant

Begrivac® BIOLOGICAL

15 ug of HA antigen; non-adjuvanted; trivalent

HIV-1 Infected Subjects Receiving Vaccine without Adjuvant; Healthy Subjects Receiving Vaccine without Adjuvant

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• For HIV-1 Infected Subjects:
• Adults between 18-60 years old (inclusive)
• Any sex or ethnicity
• Confirmed Diagnosis of HIV-1 infection
• Childbearing potential women must be willing to use an acceptable contraceptive method. Acceptable contraceptive methods are defined as one or more of the following:
• Hormone contraceptive (such as oral, injectable, transdermal patch, subcutaneous implant, cervical ring)
• Barrier (condom with spermicide or diaphragm with spermicide) at each intercourse and during the whole intercourse
• Intra-uterine device (IUD)
• 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)
• 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)

You may not qualify if:

• For HIV-1-Infected Subjects:
• Previous laboratory confirmed diagnosis of an infection by the novel H1N1 virus
• 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
• Projected life expectancy lower than 12 months
• For Healthy Adults:
• Previous laboratory confirmed diagnosis of an infection by the novel H1N1 virus
• 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)

Sponsors & Collaborators

• Chiltern Pesquisa Clinica Ltda: lead

Study Sites (2)

Centro Médico São Francisco

Curitiba, Paraná, Brazil

Location

ICG - Instituto Centro de Genomas

São Paulo, São Paulo, Brazil

Location

Related Publications (9)

• Clark TW, Pareek M, Hoschler K, Dillon H, Nicholson KG, Groth N, Stephenson I. Trial of 2009 influenza A (H1N1) monovalent MF59-adjuvanted vaccine. N Engl J Med. 2009 Dec 17;361(25):2424-35. doi: 10.1056/NEJMoa0907650. Epub 2009 Sep 10.

  PMID: 19745215 BACKGROUND

• 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

• Evison J, Farese S, Seitz M, Uehlinger DE, Furrer H, Muhlemann K. Randomized, double-blind comparative trial of subunit and virosomal influenza vaccines for immunocompromised patients. Clin Infect Dis. 2009 May 15;48(10):1402-12. doi: 10.1086/598193.

  PMID: 19361304 BACKGROUND

• Fine AD, Bridges CB, De Guzman AM, Glover L, Zeller B, Wong SJ, Baker I, Regnery H, Fukuda K. Influenza A among patients with human immunodeficiency virus: an outbreak of infection at a residential facility in New York City. Clin Infect Dis. 2001 Jun 15;32(12):1784-91. doi: 10.1086/320747. Epub 2001 May 16.

  PMID: 11360221 BACKGROUND

• Kunisaki KM, Janoff EN. Influenza in immunosuppressed populations: a review of infection frequency, morbidity, mortality, and vaccine responses. Lancet Infect Dis. 2009 Aug;9(8):493-504. doi: 10.1016/S1473-3099(09)70175-6.

  PMID: 19628174 BACKGROUND

• Ranieri R, Veronelli A, Santambrogio C, Pontiroli AE. Impact of influenza vaccine on response to vaccination with pneumococcal vaccine in HIV patients. AIDS Res Hum Retroviruses. 2005 May;21(5):407-9. doi: 10.1089/aid.2005.21.407.

  PMID: 15929703 BACKGROUND

• 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.

  PMID: 11125897 BACKGROUND

• 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.

  PMID: 10498559 BACKGROUND

• 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.

  PMID: 15905732 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Infections; Virus Diseases; Influenza, Human; HIV Infections

Interventions

focetria

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2009
• First Posted: December 15, 2009
• Study Start: April 1, 2010
• Primary Completion: September 1, 2011
• Study Completion: July 1, 2012
• Last Updated: June 5, 2013

Record last verified: 2013-06

Locations

BR (2)