Dengue FeverPhase 2NCT00617344
Immunogenicity and Safety of Three Formulations of Dengue Vaccines in Healthy Adults Aged 18 to 45 Years in the US
A Phase 2 study testing Tetravalent CYD Dengue Vaccine , 5555 formulation, Tetravalent CYD Dengue Vaccine , 5553 formulation and Tetravalent CYD Dengue Vaccine, 4444 formulation in people with Dengue Fever and Dengue Hemorrhagic Fever, run by Sanofi at 5 sites in United States.
Trial summary
This study used 3 different formulations of tetravalent CYD dengue vaccine. The primary objective of the study was to evaluate the neutralizing antibody response after 2 doses of two different formulations of tetravalent dengue vaccine administered at Month 0 and Month 6. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Dengue Fever, Dengue Hemorrhagic Fever, Dengue Virus
- What is being tested?
- Tetravalent CYD Dengue Vaccine , 5555 formulation, Tetravalent CYD Dengue Vaccine , 5553 formulation and Tetravalent CYD Dengue Vaccine, 4444 formulation
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 260 participants
- Where
- 5 sitesUnited States
- Study dates
- 17 Apr 2008to Feb 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy, as determined by medical history, clinical examination, and biological safety parameters.
- Aged 18 to 45 years on the day of inclusion.
- Provision of informed consent signed by the participant or another legally acceptable representative.
- For a woman of child-bearing potential, use of an effective method of contraception or abstinence for at least 4 weeks prior to the first vaccination, and until at least 4 weeks after the last study vaccination.
- Able to attend all scheduled visits and to comply with all trial procedures.
Who cannot join
- Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia.
- For a woman of child-bearing potential, known or suspected pregnancy or positive serum/urine pregnancy test.
- Breast-feeding woman.
- Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination.
- Planned participation in another clinical trial during the present trial period.
- Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term (at least 2 weeks within the previous 3 months) systemic corticosteroids therapy (at a dose of at least 10 mg). Topical steroids were allowed.
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- Known systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to the trial vaccine or to a vaccine containing any of the same substances.
- Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the investigator.
- Current or past alcohol abuse or drug addiction that may interfere with the participant's ability to comply with trial procedures.
- Receipt of blood or blood-derived products in the past 3 months, that might interfere with the assessment of immune response.
- Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.
- Planned receipt of any vaccine in the 4 weeks following each of the trial vaccinations.
- Human Immunodeficiency Virus (HIV), hepatitis B surface antigen, or hepatitis C virus seropositivity in blood sample taken at Screening.
- Participant deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.
- Clinically significant laboratory test abnormalities (as determined by the investigator) in blood sample taken at Screening.
- Previous residence in, travel or planned travel of more than 2 weeks during the study period to areas with high dengue infection endemicity.
- Reported history of flavivirus infection as reported by the participant.
- Previous vaccination against flavivirus diseases (including Japanese encephalitis, tick-borne encephalitis, and yellow fever).
- Flavivirus vaccination planned during the trial period.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Investigational Site 004
Hoover, Alabama, 35126
Investigational Site 001
New Orleans, Louisiana, 70119
Investigational Site 002
San Diego, California, 92103
Investigational Site 003
Springfield, Missouri, 65802
Investigational Site 005
Vallejo, California, 94589
About this study
Official title: Immunogenicity and Safety of Three Tetravalent Formulations of Dengue Vaccine Candidates in Healthy Adults Aged 18 to 45 Years in the US
This study used 3 different formulations of tetravalent CYD dengue vaccine.
The primary objective of the study was to evaluate the neutralizing antibody response after 2 doses of two different formulations of tetravalent dengue vaccine administered at Month 0 and Month 6.
The secondary objectives were:
- To evaluate the safety of the 3 formulations of tetravalent CYD dengue vaccine.
- To describe the neutralizing antibody responses to each of the 3 vaccine formulations.
- To describe vaccine viremia after the first and second dose of each of the 3 vaccine formulations in a subset of participants.
Read the detailed description
All participants provided blood samples for immunogenicity assessments, while vaccine viremia was assessed in a subset of participants in each group.
Safety was assessed in all participants as follows: solicited adverse event (AE) prelisted in the diary card were collected for 7 days after vaccination for solicited injection site reactions and 14 days for solicited systemic reactions , unsolicited AEs were collected for 28 days after vaccination, and serious adverse event (SAE) information collected throughout the study up to 6 months after vaccination.
- Conditions
- Dengue Fever, Dengue Hemorrhagic Fever, Dengue Virus
- Being tested
- Tetravalent CYD Dengue Vaccine , 5555 formulation, Tetravalent CYD Dengue Vaccine , 5553 formulation, Tetravalent CYD Dengue Vaccine, 4444 formulation
- Keywords
- Dengue fever, Dengue hemorrhagic fever, Dengue virus
- Medical subject headings
- Dengue, Severe Dengue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tetravalent CYD Dengue Vaccine , 5555 formulationBiological
A 0.5 mL dose, Subcutaneous at 0, 6, and 12 months, respectively.
Tetravalent CYD Dengue Vaccine , 5553 formulationBiological
A 0.5 mL dose, Subcutaneous at 0, 6, and 12 months, respectively
Tetravalent CYD Dengue Vaccine, 4444 formulationBiological
A 0.5 mL dose, Subcutaneous at 0, 6, and 12 months, respectively
| Study group | Role | What they receive |
|---|---|---|
| CYD Dengue Vaccine 5555 Formulation | Experimental | Participants received 3 doses of CYD dengue vaccine (5555 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. Receives: Biological: Tetravalent CYD Dengue Vaccine , 5555 formulation |
| CYD Dengue Vaccine 5553 Formulation | Experimental | Participants received 3 doses of CYD dengue vaccine (5553 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. Receives: Biological: Tetravalent CYD Dengue Vaccine , 5553 formulation |
| CYD Dengue Vaccine 4444 Formulation | Experimental | Participants received 3 doses of CYD dengue vaccine (4444 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. Receives: Biological: Tetravalent CYD Dengue Vaccine, 4444 formulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Antibody Titers of >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain: CYD Vaccine 5555 and 5553 Formulation
Percentage of participants with antibody titers >= 10 (1/dil) against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by dengue plaque reduction neutralization test (PRNT).
Measured: Pre-injection 1 (Day 0), 30 days post-injection 2 (Month 7)
Secondary outcomes (6)
Percentage of Participants With Antibody Titers of >=10 1/Dil Against Each Dengue Virus Serotype Strain
Percentage of participants with antibody titers >= 10 1/dil against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by PRNT.
Measured: Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13)
Percentage of Participants With Antibody Titers >=10 1/Dil Against At Least Any 1, 2, 3 or All 4 Dengue Virus Serotypes
Percentage of participants with antibody titers >= 10 1/dil against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by PRNT. In this outcome measure, participants with antibody titers >= 10 1/dil against any 1 of the 4 serotypes or any 2 of the 4 serotypes or any 3 of the 4 serotypes or with all 4 serotypes were reported.
Measured: Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13)
Geometric Means of Titers of Antibodies Against Each Dengue Virus Serotype Strain
Geometric mean titers against each dengue virus serotype (1, 2, 3 and 4) strain was measured by PRNT.
Measured: Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13)
Number of Participants With Solicited Injection Site Reactions After Any Vaccination
Solicited injection site reactions: Pain, Erythema, and Swelling. Pain: Grade 1: Easily tolerated, Grade 2: Sufficiently discomforting to interfere with normal behavior or activities, Grade 3: Incapacitating, unable to perform usual activities. Erythema:- Grade 1: <2.5 cm, Grade 2: >=2.5 to <5 cm, Grade 3: >=5 cm. Swelling:- Grade 1: <2.5 cm, Grade 2: >=2.5 to <5 cm, Grade 3: >=5 cm.
Measured: 7 days after any injection 1, 2 or 3
Number of Participants With Solicited Systemic Reactions After Any Vaccination
Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Fever: - Grade1: >=37.5°C to <=38.0°C (>=99.5°F to <=100.4°F), Grade 2: >38.0°C to <=39.0°C (>100.4°F to <= 102.2°F), Grade 3: >39.0°C (>102.2°F). Headache, malaise, myalgia and asthenia: Grade 1: noticeable but does not interfere with daily activities, Grade 2: interferes with daily activities, Grade 3: prevents daily activities.
Measured: 14 days after any injection 1, 2 or 3
Number of Participants With Vaccine Viremia
Vaccine viremia (level of vaccine virus in blood samples taken from participants) was measured by an assay yellow fever reverse transcriptase polymerase chain reaction which allowed the detection of vaccine viremia of any serotype (1, 2, 3 and 4).
Measured: 7 days post-injection 1 and 2, 14 days post-injection 1 and 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2008 (estimated)
- Study start17 Apr 2008
- Primary completionDec 2009
- Study completionFeb 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Dengue FeverStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 260 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi Pasteur, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00617344
- Sponsor's protocol ID
- CYD12
- Status last verified
- May 2019
- First submitted
- 6 Feb 2008
- Last updated
- 11 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Dayan GH, Thakur M, Boaz M, Johnson C. Safety and immunogenicity of three tetravalent dengue vaccine formulations in healthy adults in the USA. Vaccine. 2013 Oct 17;31(44):5047-54. doi: 10.1016/j.vaccine.2013.08.088. Epub 2013 Sep 7.
PubMed 24021313
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunogenicity and Safety of Three Tetravalent Formulations of Dengue Vaccine Candidates in Healthy Adults Aged 18 to 45 Years in the US
- ClinicalTrials.gov ID
- NCT00617344
- Acronym / sponsor ID
- CYD12
- Conditions
- Dengue Fever, Dengue Hemorrhagic Fever, Dengue Virus
- Keywords
- Dengue fever, Dengue hemorrhagic fever, Dengue virus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 260 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- 17 Apr 2008 (actual)
- Primary completion
- Dec 2009 (actual)
- Study completion
- Feb 2010 (actual)
- First posted
- 18 Feb 2008 (estimated)
- Results
- Posted 11 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study used 3 different formulations of tetravalent CYD dengue vaccine.
The primary objective of the study was to evaluate the neutralizing antibody response after 2 doses of two different formulations of tetravalent dengue vaccine administered at Month 0 and Month 6.
The secondary objectives were:
- To evaluate the safety of the 3 formulations of tetravalent CYD dengue vaccine.
- To describe the neutralizing antibody responses to each of the 3 vaccine formulations.
- To describe vaccine viremia after the first and second dose of each of the 3 vaccine formulations in a subset of participants.
Detailed description
All participants provided blood samples for immunogenicity assessments, while vaccine viremia was assessed in a subset of participants in each group.
Safety was assessed in all participants as follows: solicited adverse event (AE) prelisted in the diary card were collected for 7 days after vaccination for solicited injection site reactions and 14 days for solicited systemic reactions , unsolicited AEs were collected for 28 days after vaccination, and serious adverse event (SAE) information collected throughout the study up to 6 months after vaccination.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| CYD Dengue Vaccine 5555 Formulation | Experimental | Biological: Tetravalent CYD Dengue Vaccine , 5555 formulationParticipants received 3 doses of CYD dengue vaccine (5555 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. |
| CYD Dengue Vaccine 5553 Formulation | Experimental | Biological: Tetravalent CYD Dengue Vaccine , 5553 formulationParticipants received 3 doses of CYD dengue vaccine (5553 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. |
| CYD Dengue Vaccine 4444 Formulation | Experimental | Biological: Tetravalent CYD Dengue Vaccine, 4444 formulationParticipants received 3 doses of CYD dengue vaccine (4444 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Healthy, as determined by medical history, clinical examination, and biological safety parameters.
- Aged 18 to 45 years on the day of inclusion.
- Provision of informed consent signed by the participant or another legally acceptable representative.
- For a woman of child-bearing potential, use of an effective method of contraception or abstinence for at least 4 weeks prior to the first vaccination, and until at least 4 weeks after the last study vaccination.
- Able to attend all scheduled visits and to comply with all trial procedures.
Key exclusion criteria (19 listed)
- Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia.
- For a woman of child-bearing potential, known or suspected pregnancy or positive serum/urine pregnancy test.
- Breast-feeding woman.
- Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination.
- Planned participation in another clinical trial during the present trial period.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tetravalent CYD Dengue Vaccine , 5555 formulationA 0.5 mL dose, Subcutaneous at 0, 6, and 12 months, respectively. | Biological | CYD Dengue Vaccine 5555 Formulation |
| Tetravalent CYD Dengue Vaccine , 5553 formulationA 0.5 mL dose, Subcutaneous at 0, 6, and 12 months, respectively | Biological | CYD Dengue Vaccine 5553 Formulation |
| Tetravalent CYD Dengue Vaccine, 4444 formulationA 0.5 mL dose, Subcutaneous at 0, 6, and 12 months, respectively | Biological | CYD Dengue Vaccine 4444 Formulation |
Primary outcome
Percentage of Participants With Antibody Titers of >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain: CYD Vaccine 5555 and 5553 Formulation
Time frame: Pre-injection 1 (Day 0), 30 days post-injection 2 (Month 7)
Percentage of participants with antibody titers >= 10 (1/dil) against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by dengue plaque reduction neutralization test (PRNT).
6 secondary outcomes
Percentage of Participants With Antibody Titers of >=10 1/Dil Against Each Dengue Virus Serotype Strain
Time frame: Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13)
Percentage of Participants With Antibody Titers >=10 1/Dil Against At Least Any 1, 2, 3 or All 4 Dengue Virus Serotypes
Time frame: Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13)
Geometric Means of Titers of Antibodies Against Each Dengue Virus Serotype Strain
Time frame: Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13)
Number of Participants With Solicited Injection Site Reactions After Any Vaccination
Time frame: 7 days after any injection 1, 2 or 3
Number of Participants With Solicited Systemic Reactions After Any Vaccination
Time frame: 14 days after any injection 1, 2 or 3
Number of Participants With Vaccine Viremia
Time frame: 7 days post-injection 1 and 2, 14 days post-injection 1 and 2
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24021313Dayan GH, Thakur M, Boaz M, Johnson C. Safety and immunogenicity of three tetravalent dengue vaccine formulations in healthy adults in the USA. Vaccine. 2013 Oct 17;31(44):5047-54. doi: 10.1016/j.vaccine.2013.08.088. Epub 2013 Sep 7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi Pasteur, a Sanofi Company
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tetravalent CYD Dengue Vaccine , 5555 formulation, Tetravalent CYD Dengue Vaccine , 5553 formulation and Tetravalent CYD Dengue Vaccine, 4444 formulation in people with Dengue Fever and Dengue Hemorrhagic Fever, run by Sanofi at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Antibody Titers of >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain: CYD Vaccine 5555 and 5553 Formulation (time frame: Pre-injection 1 (Day 0), 30 days post-injection 2 (Month 7)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00617344, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2019.