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 Invasive Solid Tumors

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 Invasive Solid Tumors

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 Solid Invasive Tumors 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.

Study Overview

• Status: Completed
• Conditions: H1N1 Influenza Virus; Invasive Solid Tumors
• Intervention / Treatment: Biological: adjuvanted A(H1N1) influenza vaccine; Biological: non-adjuvanted A(H1N1) influenza vaccine; Biological: non-adjuvanted A(H1N1) influenza vaccine

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • MG
    • Belo Horizonte, MG, Brazil
      • BIOCANCER Clinical Research
  • SP
    • Santo André, SP, Brazil
      • Centro de Estudos e Pesquisas de Oncologia e Hematologia da Faculdade de Medicina da Fundação do ABC
    • São Paulo, SP, Brazil
      • Universidade Federal de Sao Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

For Invasive Solid Tumor Subjects:

• Subjects between 2 and 70 years of age (inclusive)
• Any sex or ethnicity
• Confirmed diagnosis of Invasive Solid Tumor or hematological malignancies in complete remission for at least 3 months and not more than 18 months after the last neo-adjuvant and/or adjuvant chemotherapy cycle according to investigators assessment and the subjects medical records
• Previous use of neo-adjuvant and/or adjuvant chemotherapy for the treatment on an invasive solid tumor
• Life expectancy of at least 12 months
• Karnofsky Performance Scale > 40%

• 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).
• Subjects capable of following 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 sign the consent form
• In case of children and adolescents (below 18 years of age): Subjects capable of understanding the nature of the study and whose legal guardian understands the nature and risk of the study proposed and signs the consent form
• The study subjects may have other underlying chronic diseases that do not involve immunosuppression (e.g. osteoarticular diseases, cardiorespiratory diseases, metabolic diseases, stable, non progressive, non-severe neurologic disorders without cognitive impairment, ophthalmologic diseases, etc.), but their symptoms/signs must be under control through medical follow-ups and drug therapy

For Healthy Subjects:

• Subjects between 2 and 70 years of age (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 sign the consent form
• In case of children and adolescents (below 18 years of age): Subjects capable of understanding the nature of the study and whose legal guardian understands the nature and risk of the study proposed and signs the consent form

Exclusion Criteria:

For Invasive Solid Tumor Subjects:

• Previous laboratory confirmed diagnosis of an infection by the novel H1N1 virus
• Administration of other 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)
• Presence of other diseases, not related to cancer with confirmed immunosuppression
• Chemotherapy, biologic therapy or radiation within 3 months prior to inclusion in the study
• History of chronic hepatic or renal disease
• 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
• Receipt of any investigational product within 12 months prior to inclusion in the study

For Healthy Subjects:

• Previous laboratory confirmed diagnosis of an infection by the new virus H1N1
• Receipt of another vaccine against the new virus H1N1 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: High Risk Population; Each subject will receive two doses of the assigned vaccine, the first on Study Day 1, and the second on Study Day 22	Biological: adjuvanted A(H1N1) influenza vaccine; 7.5 ug of HA antigen; adjuvanted; monovalent
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	Biological: non-adjuvanted A(H1N1) influenza vaccine; 15ug of HA antigen, non-adjuvanted; trivalent; Biological: non-adjuvanted A(H1N1) influenza vaccine; 15 mcg of antigen; non-adjuvanted; trivalent
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	Biological: adjuvanted A(H1N1) influenza vaccine; 7.5 ug of HA antigen; adjuvanted; monovalent
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	Biological: non-adjuvanted A(H1N1) influenza vaccine; 15ug of HA antigen, non-adjuvanted; trivalent; Biological: non-adjuvanted A(H1N1) influenza vaccine; 15 mcg of antigen; non-adjuvanted; trivalent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary objective of this study is to determine the optimal influenza vaccination strategy in patients with invasive solid tumors	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Assess whether the adjuvanted vaccine offers a meaningful benefit in relation to the non-adjuvanted vaccine in this at-risk population	3 months
Assess whether two doses of either study vaccine will provide meaningful benefit in comparison to one dose	3 months
Assess the persistence of antibody levels in the two vaccine groups	3 months
Gain further insight into the safety of the adjuvanted and non-adjuvanted H1N1 vaccines in this high-risk patient population	3 months

Collaborators and Investigators

• Sponsor: Chiltern Pesquisa Clinica Ltda

Publications and helpful links

General Publications

• 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.
• 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.
• 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. Erratum In: N Engl J Med. 2009 Jul 2;361(1):102.
• Gross PA, Gould AL, Brown AE. Effect of cancer chemotherapy on the immune response to influenza virus vaccine: review of published studies. Rev Infect Dis. 1985 Sep-Oct;7(5):613-8. doi: 10.1093/clinids/7.5.613.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: December 14, 2009
• First Submitted That Met QC Criteria: December 14, 2009
• First Posted (Estimate): December 15, 2009

Study Record Updates

• Last Update Posted (Estimate): September 13, 2012
• Last Update Submitted That Met QC Criteria: September 12, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: tolerability; safety; oncology; Immunogenicity; Virus Diseases; tumors; Influenza, Human; H1N1; Influenza A Virus
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: V111_15TP