Safety and Immunogenicity of Various Formulations of Live Attenuated Tetravalent Dengue Vaccine in Healthy US Adults

NCT ID: NCT00350337

Last Updated: 2021-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-04-05
• Study Completion Date: 2008-03-13

Brief Summary

This descriptive study will evaluate the safety and immunogenicity of 3 different formulations of the WRAIR dengue vaccine compared to a placebo.

Detailed Description

Subjects will be randomized into one of 4 groups. One group will receive a placebo vaccine and the others will receive one of 3 different dengue vaccine formations. Each subject will receive two doses six months apart. Study subjects who elect to participate in a mosquito transmissibility component of the study will undergo mosquito feedings during each of the two assigned follow-up visits after vaccine dose 1. All subjects will have 11 venipunctures during 11 visits (i.e., screening plus 10 study visits) over a period of nine months.

A third (booster) dose of post transfection F17 or F19 will be administered approximately 5 to 12 months after dose 2 to all subjects who received one of these formulation for their first two doses. Volunteers will return for a single visit 6 months after receiving their booster dose (long term follow-up)

Conditions

Dengue

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Pre-transfection F17

4 monovalent vaccine lots: DEN type 1 45AZ5 PDK-27, Lot 1-1-90 DEN type 2 S16803 PDK-50, Lot 1-1-90 DEN type 3 CH53489 PDK-20 DEN type 4 341750 PDK-6, Lot 1-1-90 in 50% EMEM stabilizer, streptomycin, neomycin and vegetable-derived carbohydrates and amino acids stabilizers for injection.

Freeze-dried monovalent dengue vaccines were rehydrated with sterile water for injection diluted to match viral concentration of the F17 Post vaccine

Group Type: EXPERIMENTAL

Pre-transfection F17

Intervention Type: BIOLOGICAL

Dengue tetravalent Vaccine F17 Pre transfection: 0.5 mL volume per dose, administered at 0 and 6 months via subcutaneous injection

Post-transfection F17

4 monovalent vaccine lots: DEN type 1: 4.9 log10 FFU/mL DEN type 2 : 5.3 log10 FFU/mL DEN type 3: 4.7 log10 FFU/mL DEN type 4: 5.0 log10 FFU/mL in 50% EMEM stabilizer, streptomycin, neomycin and vegetable-derived carbohydrates and amino acids stabilizers for injection.

Lyophilized, single dose vials and sterile water for injection

Group Type: EXPERIMENTAL

Post-transfection F17

Intervention Type: BIOLOGICAL

Dengue tetravalent Vaccine F17 Post transfection: 0.5 mL volume per dose, administered at 0 and 6 months via subcutaneous injection. For the booster phase of the study, a booster dose was administered at five months to one year following the second dose.

Post-transfection F19

4 monovalent vaccine lots: DEN type 1: 4.9 log10 FFU/mL DEN type 2: 5.2 log10 FFU/mL DEN type 3: 4.6 log10 FFU/mL DEN type 4: 4.4 log10 FFU/mL (1:10 dilution) in 50% EMEM-stabilizer, streptomycin, neomycin and vegetable-derived carbohydrates and amino acids stabilizers for injection.

Lyophilized, single dose vials and sterile water for injection

Group Type: EXPERIMENTAL

Post-transfection F19

Intervention Type: BIOLOGICAL

Dengue tetravalent Vaccine F19 Post transfection: 0.5 mL volume per dose, administered at 0 and 6 months via subcutaneous injection. For the booster phase of the study, a booster dose was administered at five months to one year following the second dose.

Placebo

A sterile solution of the same EMEM, with phenol red (1:1) and the same virus stabilizer contained in the vaccine. The phenol red dye (phenolsulfonphthalein) is an FDA-accepted vaccine excipient used in vaccines as a pH indicator. The placebo was identical in appearance to the dengue vaccine.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Sterile solution of buffered water (0.9% NaCl), U.S. FDA accepted vaccine excipient, phenol red dye(phenolsulfonphthalein, used in vaccines as a pH indicator); 0.5 mL volume per dose, administered at 0 and 6 months via subcutaneous injection

Interventions

Pre-transfection F17

Dengue tetravalent Vaccine F17 Pre transfection: 0.5 mL volume per dose, administered at 0 and 6 months via subcutaneous injection

Intervention Type: BIOLOGICAL

Post-transfection F17

Dengue tetravalent Vaccine F17 Post transfection: 0.5 mL volume per dose, administered at 0 and 6 months via subcutaneous injection. For the booster phase of the study, a booster dose was administered at five months to one year following the second dose.

Intervention Type: BIOLOGICAL

Post-transfection F19

Dengue tetravalent Vaccine F19 Post transfection: 0.5 mL volume per dose, administered at 0 and 6 months via subcutaneous injection. For the booster phase of the study, a booster dose was administered at five months to one year following the second dose.

Intervention Type: BIOLOGICAL

Placebo

Sterile solution of buffered water (0.9% NaCl), U.S. FDA accepted vaccine excipient, phenol red dye(phenolsulfonphthalein, used in vaccines as a pH indicator); 0.5 mL volume per dose, administered at 0 and 6 months via subcutaneous injection

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• A healthy male or female adult 18-45 years at the time of vaccination;
• Free of obvious health problems as established by medical history and physical examination before entering into the study;
• Written informed consent obtained from the subject;
• Able to read the Subject Information Sheet and Consent Form;
• Subjects who the investigator believes can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits) should be enrolled in the study;
• If the subject is female, she must be of non-childbearing potential, i.e. either surgically sterilized or one year post-menopausal; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions (i.e. intrauterine contraceptive device; oral contraceptives or other equivalent hormonal contraception, e.g. progestin implantable, cutaneous hormonal patch or injectable contraceptives) for 30 days prior to vaccination, have a negative pregnancy test within 48 hours prior to vaccination and must agree to continue such precautions for 60 days after completion of the vaccination series.

Exclusion Criteria

• Pregnant or lactating female;
• Female planning to become pregnant or planning to discontinue abstinence or contraceptive precautions;
• History of any neurological or behavioral disorder or seizures, with the exception of a single febrile seizure in childhood;
• History of drug abuse or alcohol consumption (more than 2 drinks per day);
• History of allergic disease/reaction likely to be exacerbated by any component of the vaccine;
• History of urticaria related to mosquito bites requiring medical attention;
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, renal, hematologic or endocrine functional defect, as determined by physical examination or laboratory tests;
• Any confirmed or suspected immunosuppressive or immunodeficient condition;
• Subject seropositive for HBsAg, anti-HCV or anti-HIV;
• Acute disease at the time of enrollment (acute disease is defined as the presence of a moderate or severe illness with or without fever);
• (Vaccine can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e., oral temperature <37.5°C/<99.5°F.)
• Chronic hepatomegaly, right upper quadrant abdominal pain or tenderness;
• Chronic splenomegaly, left upper quadrant abdominal pain or tenderness;
• Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 days preceding the study vaccine (includes placebo) or planned use during the study period;
• Planned administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before each dose of the study vaccine and ending 30 days after;
• A planned move to a location that will prohibit participating in the trial for 9 months after the initial vaccination;
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 90 days preceding the first dose or planned administration during the study period. For corticosteroids, this will mean prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed;
• Administration of immunoglobulins and/or blood products within 90 days preceding the first dose or planned administration during the study period;
• Any chronic systemic drug therapy to be continued during the study period (except for vitamin/mineral supplements, a single anti-hypertension medication or routine treatment for gastro-esophageal reflux).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Walter Reed Army Institute of Research (WRAIR)

FED

Sponsor Role: collaborator

U.S. Army Medical Research and Development Command

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen J Thomas, MD, FACP

Role: PRINCIPAL_INVESTIGATOR

Walter Reed Army Institute of Research (WRAIR)

Locations

Walter Reed Army Institute of Research

Silver Spring, Maryland, United States

Countries

United States

References

Thomas SJ, Eckels KH, Carletti I, De La Barrera R, Dessy F, Fernandez S, Putnak R, Toussaint JF, Sun W, Bauer K, Gibbons RV, Innis BL. A phase II, randomized, safety and immunogenicity study of a re-derived, live-attenuated dengue virus vaccine in healthy adults. Am J Trop Med Hyg. 2013 Jan;88(1):73-88. doi: 10.4269/ajtmh.2012.12-0361. Epub 2012 Dec 3.

Reference Type: DERIVED

PMID: 23208878 (View on PubMed)

Other Identifiers

GSK 103996

Identifier Type: OTHER

Identifier Source: secondary_id

HSRRB A-13291

Identifier Type: OTHER

Identifier Source: secondary_id

WRAIR 1151

Identifier Type: -

Identifier Source: org_study_id