Needle-Free Jet Injection of Reduced-Dose, Intradermal, Influenza Vaccine in >= 6 to < 24-Month-Old Children - Full Text View

Sponsors and Collaborators:	Centers for Disease Control and Prevention Fundación Dominicana de Infectología, Santo Domingo, Dominican Republic Hospital Infantíl Dr. Robert Reid Cabral, Santo Domingo, Dominican Republic World Health Organization Pan American Health Organization Program for Appropriate Technology in Health, Seattle, WA, USA Bioject Medical Technologies, Inc. Sanofi Pasteur SA [vaccine donor]
Information provided by:	Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:	NCT00386542

Purpose

This is a sequential phase I and II, controlled, double-blinded study to determine whether immune responses suggesting protection against influenza can safely be induced in young children by two reduced doses one month apart of 0.1 mL of a trivalent inactivated influenza vaccine (INF) administered by the intradermal (ID) route with an investigational ID spacer on a United States (U.S.)-licensed needle-free jet injector (JI), compared to two standard intramuscular (IM) 0.25 mL doses by needle-syringe (N-S) in this age group. The locale is a developing country where financial restraints for the use of full-dose influenza vaccine would limit protection from an influenza pandemic threat, where N-Ss pose dangers and drawbacks in clinical use, and where Mantoux-type N-S ID injections are difficult to administer during mass campaigns.

Condition	Intervention	Phase
Influenza	Biological: Vaxigrip® trivalent inactivated influenza vaccine Device: Intradermal spacer on Biojector® 2000 jet injector	Phase I Phase II

MedlinePlus related topics: Flu

Drug Information available for: Influenza Vaccines Fluvirin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Dose Comparison, Parallel Assignment, Safety/Efficacy Study
Official Title:	Clinical Trial of Safety (Reactogenicity) and Immunogenicity of Needle-Free Jet Injection of Reduced-Dose, Intradermal Influenza Vaccine (INF) Administered to >= 6 to < 24 Month-Old Infants and Toddlers in the Dominican Republic

Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:

Rates of seroconversion (SC) on HI assay 1 month after dose 2. SC defined as titer >= 40 among initial-seronegatives (titer < 8 on day 0); OR, a followup titer which rises >= 4-fold. [ Designated as safety issue: No ]

Secondary Outcome Measures:

Rates of local and systemic reactions [ Designated as safety issue: Yes ]
Seroprotection (SP) on HI assay, defined as >= 40 regardless of baseline [ Designated as safety issue: No ]
Geometric mean titers (GMT) on HI [ Designated as safety issue: No ]
Geometric mean increase (GMI) on HI [ Designated as safety issue: No ]

Estimated Enrollment:	450
Study Start Date:	October 2006
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
ID-JI-0.1: Experimental Group "ID-JI-0.1" (n = 16) - reduced 0.1 mL INF doses administered intradermally (ID) by needle-free jet injector (JI) (Biojector® 2000 subcutaneous syringe no. 2 [green color code], with 2 cm investigational spacer, Bioject Medical Technologies, Inc., Portland, OR, USA)	Biological: Vaxigrip® trivalent inactivated influenza vaccine See full description elsewhere in this record. Device: Intradermal spacer on Biojector® 2000 jet injector See elsewhere in this record for full description.
IM-NS-0.1: Active Comparator Group "IM-NS-0.1" (n = 16) - reduced 0.1 mL INF doses administered intramuscularly (IM) needle-syringe (NS) (via 22-25 gauge needle, minimum 25 mm/1-inch length)	Biological: Vaxigrip® trivalent inactivated influenza vaccine See full description elsewhere in this record.
IM-NS-0.25 control: Active Comparator Group "IM-NS-0.25" (controls) (n = 16) - full 0.25 mL INF doses administered intramuscularly (IM) by needle-syringe (NS) (22-25 gauge needle, minimum 25 mm/1-inch length)	Biological: Vaxigrip® trivalent inactivated influenza vaccine See full description elsewhere in this record.

Detailed Description:

Randomized, observer-blinded, clinical pilot (phase I) trial of safety, followed by a clinical (phase II) trial of safety and non-inferiority of immune response to the standard route and dose for the merged subjects from both phases.

Phase I - Influenza-vaccine naïve children (n = 48) aged >= 6 to < 24 months will be randomized in a 1:1:1 ratio to the following three study arms, each to receive two doses on days 0 and 28 of trivalent inactivated influenza (INF) vaccine (Vaxigrip®, Sanofi Pasteur, Lyon, France) into the left thigh (< 12 months) or left deltoid (≥ 12 months):

Group "ID-JI-0.1" (n = 16) - reduced 0.1 mL INF doses administered intradermally (ID) by needle-free jet injector (JI) (Biojector® 2000 subcutaneous syringe no. 2 [green color code], with 2 cm investigational spacer, Bioject Medical Technologies, Inc., Portland, OR, USA)
Group "IM-NS-0.1" (n = 16) - reduced 0.1 mL INF doses administered intramuscularly (IM) needle-syringe (NS) (via 22-25 gauge needle, minimum 25 mm/1-inch length)
Group "IM-NS-0.25" (controls) (n = 16) - full 0.25 mL INF doses administered intramuscularly (IM) by needle-syringe (NS) (22-25 gauge needle, minimum 25 mm/1-inch length)

Phase II - Upon assessment of the safety profile from phase I by the unblinded Data Safety Monitoring Board (DSMB), with its approval an additional 402 children will be recruited and randomized (134 per group) as in phase I above. Total subjects in phase I and II = 450 (150 in each of three study arms).

Adverse Event Diaries: Parents will be trained to complete a diary form to observe, measure, and record solicited local reactions for the injection site and systemic signs and symptoms for the child for days 0 through 7 after vaccination, plus unsolicited symptoms, illness, and medications for days 0 through 28.

Followup: Return clinic visits will be scheduled on days 2, 7, and 28 after INF dose 1, at which times the diary card data will be recorded by staff and the card collected on day 28. Upon receiving dose 2 of vaccine, patients will be scheduled again to return to the study center 2, 7, and 28 days afterwards. The same procedures as for dose 1 regarding diary cards, telephone followup, and home visits will apply after dose 2.

Upon returning to clinic on day 28 after dose 2 (day 56 after dose 1), the child will receive an unblinded, "insurance", full-volume, 0.25 mL dose (#3) of influenza vaccine by NS IM, unless he or she is in the full-dose IM control group IM-NS-0.25, in which case a mock injection will be administered instead of a 3rd full dose beyond the usual 2-dose series. All participants will return 6 months after this third injection for a fourth "bonus" dose of influenza vaccine to ensure protection for the following season.

Serum Collection: Blood specimens to measure serologic responses will be collected three times, just prior to vaccination on day 0 (INF dose 1), on day 28 (INF dose 2), and on day 56 (INF "insurance" dose 3).

Ethical oversight additional to CDC IRB G by (1) World Health Organization Research Ethics Review Committee, (2) Consejo Nacional de Bioética en Salud, and (3) Fundación Dominicana de Infectología Comité de Etica/Investigaciones.

Eligibility

Ages Eligible for Study:	6 Months to 24 Months
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Age from > = 6 to < 24 months (not having reached 2nd birthday).
Born after a full-term (≥ 37 weeks), and birth weight of >= 2.5 kg (>= 5 pounds, 8 ounces)
History of prior or first attendance as a patient, or as a sibling of a patient, seeking routine immunization or other clinical care at the Hospital Infantíl Robert Reid Cabral (HIRRC)
The parent(s) or legal guardian(s) provide(s) written informed consent and agree(s) to bring the infant back to the clinic for all visits scheduled in the study
Up-to-date for routine doses of vaccines officially recommended for the patient's age in the Dominican Republic to prevent tuberculosis, polio, diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae B
In good health, as determined by medical history and physical examination collected in accordance with the Case Report Form (CRF), and by the clinical judgment of the investigators.

Exclusion Criteria:

Infants WHOSE PARENT(S)/LEGAL GUARDIAN(S):

Are unable or unwilling to give written informed consent for their infant to participate in the study
Cannot be contacted by telephone (family's own or a neighbor's) if necessary for adverse events if scheduled followup return appointments are missed
Are unable to complete the diary for adverse events; are unable to measure and record temperatures or maximal diameter of local reactions or limb circumference; or have difficulty understanding written instructions; or other factors which indicate exclusion in the judgement of the study staff.

INFANTS who:

Have fever (by parental report or by rectal temperature ≥ 38.5° C or axillary ≥ 38.0° C) currently or within the past 3 days, or who are currently suffering from an acute or chronic infectious disease (including known HIV)
Have had an acute or chronic infection requiring systemic antimicrobial therapy (antibiotic or antiviral) or other prescribed treatment within the past 21 days. This includes any underlying illness that may limit their response to vaccination, such as those receiving intravenous immunoglobulin for agammaglobulinemia, or systemic steroid therapy.
Are malnourished, defined by weight less than two standard deviations below the median weight for their age
Are allergic to eggs, or have a history of any anaphylactic shock, asthma, urticaria, or other allergic reaction after previous vaccinations, or have allergy or hypersensitivity to any component of the study vaccine
Have ever previously received any influenza vaccine
Have received within the prior 28 days, or for whom there is the indication to receive in the next 56 days, any non-study vaccination or investigational agent outside of the study
Have a known bleeding diathesis, or any condition with a prolonged bleeding time
Currently have any serious confirmed or suspected disease, such as metabolic, cardiac, or autoimmune disease, or diabetes
Have a history of epilepsy or a seizure disorder, or neurodevelopmental disorders such as autism
Have a genetic anomaly or known cytogenic disorder (e.g., Down's syndrome)
Have leukemia, lymphoma, or any other cancer/neoplasm
Have known or suspected immune dysfunction, including HIV infection, or receives(ed) immunosuppressive therapy, including systemic corticosteroids
Have ever received blood, blood products, or parenteral preparations of immunoglobulin
Have any other serious disease (e.g., with signs of cardiac or renal failure), including progressive neurologic disease
Have any condition which, in the opinion of the investigator, may interfere in the evaluation of the objectives of the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00386542

Contacts

Contact: Jesús M Feris Iglesias, MD	+1 (809) 532-5872	infectologia@codetel.net.do
Contact: Virgen Gómez, MD	+1 (809) 449-2913	virgen.gomez@codetel.net.do

Locations

Dominican Republic, Distrito Nacional
Hospital Infantíl Dr. Robert Reid Cabral	Recruiting
Santo Domingo, Distrito Nacional, Dominican Republic
Sub-Investigator: Jacqueline Sánchez, MD
Sub-Investigator: Glenny Gúzman, MD

Sponsors and Collaborators

Centers for Disease Control and Prevention

Fundación Dominicana de Infectología, Santo Domingo, Dominican Republic

Hospital Infantíl Dr. Robert Reid Cabral, Santo Domingo, Dominican Republic

World Health Organization

Pan American Health Organization

Program for Appropriate Technology in Health, Seattle, WA, USA

Bioject Medical Technologies, Inc.

Sanofi Pasteur SA [vaccine donor]

Investigators

Principal Investigator:	Bruce G Weniger, MD, MPH	Immunization Safety Office, Centers for Disease Control and Prevention
Study Director:	Virgen Gómez, MD	Hospital Infantíl Dr. Robert Reid Cabral
Study Director:	Jesús M Feris Iglesias, MD	Hospital Infantíl Dr. Robert Reid Cabral
Study Director:	Josefina Fernández, MD	Hospital Infantíl Dr. Robert Reid Cabral
Study Director:	Pedro Moro, MD, MPH	Immunization Safety Office, Centers for Disease Control and Prevention
Study Chair:	Martin Friede, PhD	Initiative for Vaccine Research, World Health Organization

More Information

Hospital Infantíl Dr. Robert Reid Cabral, Department of Infectious Diseases (also see: http://www.cdc.gov/od/science/iso/vaxtech/nfit/) This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

Responsible Party:	Centers for Disease Control and Prevention (CDC) ( Bruce G. Weniger, MD, MPH, Chief, Vaccine Technology, Immunization Safety Office )
Study ID Numbers:	CDC-ISO-4785
Study First Received:	October 10, 2006
Last Updated:	July 30, 2008
ClinicalTrials.gov Identifier:	NCT00386542
Health Authority:	United States: Federal Government; Dominican Republic: Secretaría del Estado de Salud Pública y Asistencia Social (SESPAS)

Keywords provided by Centers for Disease Control and Prevention:

vaccination
influenza vaccine
jet injection
intradermal injection
infancy
children
Dominican Republic
pandemic preparedness
dose-sparing

reduced dosage
immunogenicity
reactogenicity
safety
needle-free
immune response
hemagglutination inhibition
Infant

Study placed in the following topic categories:

Virus Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Influenza, Human
Orthomyxoviridae Infections

Additional relevant MeSH terms:

RNA Virus Infections

ClinicalTrials.gov processed this record on January 16, 2009