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

NCT00350337 | Completed Phase 2 Results

• 3 other identifiers: WRAIR 1151GSK 103996HSRRB A-13291
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Dengue

Outcome Measures

Primary Outcomes (3)

• N Antibody, Geometric Mean Titer(GMT) to Dengue Serotypes 1, 2, 3 and 4

  GMTs for DEN neut. antibodies -unprimed subjects (primary and booster ATP Cohort for immunogenicity) PRE = Pre dose PI(M1) = Post dose 1, month 1 PII(M7) = Post dose 2, month 7 PRE III = Pre dose 3 PIII(M1) = Post dose 3, month 1

  Pre dose 1, 1 month post dose 1, 7 months post dose 2, Pre dose 3 and 1 month post dose 3

• Percentage of Subjects Seropositive for Dengue Serotypes 1, 2, 3 and 4

  Serpositivity rates for DEN neut. antibodies -unprimed subjects (primary and booster ATP Cohort for immunogenicity) PRE = Pre dose PI(M1) = Post dose 1, month 1 PII(M7) = Post dose 2, month 7 PRE III = Pre dose 3 PIII(M1) = Post dose 3, month 1

  Pre dose 1, 1 month post dose 1, 7 months post dose 2, Pre dose 3 and 1 month post dose 3

• Occurrence of Any, and Grade 3 Solicited Adverse Events (AEs) Within 21 Days Follow-up After Dose 1 of Study Vaccine

  Diary cards, digital thermometers, and small rulers were provided to subjects to record local and general solicited symptoms(pain, redness and swelling at the injection site, fatigue, headache, pain behind the eyes, abdominal pain, nausea, vomiting, muscle aches, joint aches, rash, photophobia and pruritis) and oral temperature taken daily for 21 days (days 0 through 20). The observations were to be recorded each evening and account for the previous 24 hours. If multiple temperature measurements were taken throughout the day, the maximum temperature was to be recorded.

  21 days following 1st vaccination dose

Secondary Outcomes (8)

• Occurrence of Any, and Grade 3 Solicited Adverse Events (AEs) Within 21 Days Follow-up After Dose 2 of Study Vaccine;

  within 21 days after vaccination

• Unsolicited Adverse Events Within 31 Days After Each Dose of Study Vaccine Dose

  within 31 days of study vaccine

• Occurrence of Serious Adverse Events (SAEs) Throughout the Entire Study Period.

  Days 0 to 270

• Occurrence of Abnormal Findings at Physical Examination After Each Vaccine Dose

  throughout the 202 day study

• Percentage of Subjects With Suspected and Confirmed Dengue Reported During the 31-day Post-vaccination Period (Total Vaccinated Cohort)

  Days 0-30 post vaccination periods (total vaccinated cohort)

Study Arms (4)

Pre-transfection F17

EXPERIMENTAL

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

Biological: Pre-transfection F17

Post-transfection F17

EXPERIMENTAL

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

Biological: Post-transfection F17

Post-transfection F19

EXPERIMENTAL

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

Biological: Post-transfection F19

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

Pre-transfection F17 BIOLOGICAL

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

Pre-transfection F17

Post-transfection F17 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 F17

Post-transfection F19 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.

Post-transfection F19

Placebo 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

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• GlaxoSmithKline: collaborator
• Walter Reed Army Institute of Research (WRAIR): collaborator

Study Sites (1)

Walter Reed Army Institute of Research

Silver Spring, Maryland, 20910, United States

Location

Related Publications (1)

• 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.

  PMID: 23208878 DERIVED

MeSH Terms

Conditions

Dengue

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Results Point of Contact

• Title: Division of Regulated Activities and Compliance Director
• Organization: United States Army Medical Materiel Development Activity

USAMRMCREGULATORYAFFAIRS@amedd.army.mil

301-619-0317

Study Officials

• Stephen J Thomas, MD, FACP

  Walter Reed Army Institute of Research (WRAIR)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2006
• First Posted: July 10, 2006
• Study Start: April 5, 2006
• Primary Completion: June 20, 2007
• Study Completion: March 13, 2008
• Last Updated: February 12, 2021
• Results First Posted: October 26, 2018

Record last verified: 2021-02

Locations

US (1)