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

United States Army Medical Research and Development Command (USAMRDC)

Status and phase: Completed; Phase 2

Conditions: Dengue

Treatments: Other: Placebo; Biological: Pre-transfection F17; Biological: Post-transfection F19; Biological: Post-transfection F17

Study type: Interventional

Funder types: Other U.S. Federal agency; Industry

Identifiers

NCT00350337

HSRRB A-13291 (Other Identifier)

GSK 103996 (Other Identifier)

WRAIR 1151

Details and patient eligibility

About

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

Full 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)

Enrollment: 86 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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).

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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86 participants in 4 patient groups, including a placebo group

Pre-transfection F17

Experimental group

Description:

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

Treatment:

Biological: Pre-transfection F17

Post-transfection F17

Experimental group

Description:

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

Treatment:

Biological: Post-transfection F17

Post-transfection F19

Experimental group

Description:

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

Treatment:

Biological: Post-transfection F19

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Other: Placebo