Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
CYD Dengue Vaccine · 10 trials · 7 indications
GMTs (measured in milli-Merck Units per mL \[mMU/mL\]) against each Gardasil HPV antigen (HPV-6, HPV-11, HPV-16, HPV-18) were assessed using competitive Luminex immunoassay (cLIA) method. Dengue immune participants at Baseline were defined as participants with titers \>=10 (1/dil) for at least one serotype with the parental dengue virus strains.
The GMTs against each of the four parental dengue virus serotypes (1, 2, 3, and 4) of CYD dengue vaccine was assessed using the 50% plaque reduction neutralization test (PRNT50) assay. Dengue immune participants at Baseline were defined as participants with titers \>=10 (1/dil) for at least one serotype with the parental dengue virus strains.
GMTs against each Cervarix HPV antigen (HPV-16 and HPV-18) were assessed using an enzyme-linked immunosorbent assay (ELISA) method. Dengue seropositive participants at baseline were defined as those participants with titers greater than or equal to (\>=) 10 (1/dilutions \[dil\]) for at least one serotype with the parental dengue virus strain.
The GMTs against each of the four parental dengue virus serotypes (Serotypes 1, 2, 3, and 4) of CYD dengue vaccine were assessed using the 50% plaque reduction neutralization test (PRNT50) assay. Dengue seropositive participants at baseline were defined as those participants with titers \>=10 (1/dil) for at least one serotype with the parental dengue virus strain.
An AE was any untoward medical occurrence in a participant administered study vaccine and which did not necessarily have a causal relationship. An unsolicited AE was an observed AE that did not fulfill the conditions pre-listed in the protocol and case report form (CRF) in terms of diagnosis and/or onset window post-vaccination.
An AE was any untoward medical occurrence in a participant administered study vaccine and which did not necessarily have a causal relationship. A solicited reaction was an expected adverse reaction (AR) observed and reported under the conditions pre-listed in the protocol and CRF and included pain, erythema, and swelling. Injection site reaction was an AR at and around the injection site. Injection site reactions were commonly inflammatory reactions.
A solicited reaction was an "expected" adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRF. Solicited systemic reactions included headache, fever, localized or topical manifestations that were not associated with the vaccination or administration site.
An unsolicited AE was an observed AE that did not fulfill the conditions pre-listed in the protocol and CRF in terms of diagnosis and/or onset window post-vaccination. An AESI was one of scientific and medical concern specific to the study vaccine, for which ongoing monitoring, and rapid communication by the Investigator to the Sponsor was appropriate. The following were considered as serious AESI: serious hypersensitivity/allergic reactions occurring in all participants within 7 days after vaccination; serious viscerotropic disease occurring in all participants within 30 days after vaccination; serious neurotropic disease occurring in all participants within 30 days after vaccination; serious dengue disease requiring hospitalization occurring in all participants at any time during the study. The following were considered as non-serious AESIs, hypersensitivity/allergic reactions occurring in all participants within 7 days after vaccination.
An AE was any untoward medical occurrence in a participant administered study vaccine and which does not necessarily have a causal relationship. SAEs were any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. Hospitalized VCD cases were defined as an acute febrile illness with diagnosis of dengue requiring hospitalization. The confirmatory dengue diagnosis was performed through virological detection.
GMTs of antibodies against each of the 4 dengue virus serotype (parental strains) were assessed using the plaque reduction neutralization test (PRNT).
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3, or 4) were assessed using plaque reduction neutralization test (PRNT) assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline was defined as participants with titers \>=10 (1/dilution) for at least 1 serotype with parental dengue virus strains. Per-protocol analysis set (PPAS) included all participants who had no protocol violations; and who met any of following study violations were excluded from PPAS (STAGE I/II): had not met all protocol-specified inclusion/exclusion criteria, had not received correct doses or injections, received vaccine other than randomized schedule, did not receive vaccination in proper time window, had not provided post-dose serology sample in proper time window, received protocol-restricted medication, therapy, or vaccine.
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers \>=10 (1/dilution) for at least one serotype with the parental dengue virus strains.
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers \>=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 1a (28 days 12 months Booster dose) were reported and compared in this outcome measure. GMT paired ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 1a: 28 days post 12 months booster dose in STAGE-II by Group 1: 28 days post-dose 3 in STAGE-I.
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers \>=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 2a (28 days post 12 months Booster dose) were reported and compared in this outcome measure. GMT ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 2a: 28 days post 12 months booster dose in STAGE-II by Group 1: 28 days Post-dose 3 in STAGE-I.
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers \>=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 1b (28 days post 24 months booster dose) were reported and compared in this outcome measure. GMT paired ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 1b: 28 days post 24 months booster dose in STAGE-II by Group 1: 28 days Post-dose 3 in STAGE-I.
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers \>=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 2b (28 days post 24 months Booster dose) was reported and compared in this outcome measure. GMT ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 2b: 28 days post 24 months booster dose in STAGE-II by Group 1: 28 days post-dose 3 in STAGE-I.
Geometric Mean Titers (GMTs) of antibodies against each of the 4 dengue virus serotype (parental strains) were assessed using the plaque reduction neutralization test (PRNT).
GMTs of antibodies against each dengue virus serotype (parental strains 1, 2, 3 and 4) were measured by plaque reduction neutralization test (PRNT). The lower limit of quantitation (LLOQ) of the assay was a titer of 10 (1/dilution).
Antibody titers against each dengue virus serotype (parental strains 1, 2, 3 and 4) were measured by PRNT.
Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT).
Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavi virus (FV) immune participants at baseline are defined as those participants with ≥ 10 1/dil for at least one serotype with the parental dengue virus strain or for Yellow Fever titer.
Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavi virus (FV) naïve participants are defined as those participants with \< 10 1/dil for all serotypes with parental dengue virus strains and for Yellow Fever titer.
Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT).
Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT).
Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT).
Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT).
Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Geometric mean titer ratio is the geometric mean of individual post vaccination/pre vaccination titer of antibodies to each parental dengue virus serotype strain.
Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavivirus-immune subjects at baseline are defined as those participants with ≥ 10 1/dil for at least one serotype with the parental dengue virus strain or for Yellow Fever titer.
Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavivirus-immune subjects at baseline are defined as those participants with ≥ 10 1/dil for at least one serotype with the parental dengue virus strain or for Yellow Fever titer. Geometric mean titer ratio is the geometric mean of individual post vaccination/pre-vaccination titer of antibodies to each parental dengue virus serotype strain.
Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavivirus-naïve participants are defined as those participants with \< 10 1/dilutions for all serotypes with parental dengue virus strains and for Yellow Fever titer.
Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavivirus-naïve participants are defined as those participants with \< 10 1/dil for all serotypes with parental dengue virus strains and for Yellow Fever titer. Geometric mean titer ratio is the geometric mean of individual post-vaccination/pre-vaccination titer of antibodies to each parental dengue virus serotype strain.
Solicited Injection-site reactions: Pain, Erythema, and Swelling. Solicited Systemic Reactions: Fever, (Temperature) Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited Injection-Site Pain, Incapacitating, unable to perform usual activities; Erythema and Swelling, ≥ 5 cm. Grade 3 Solicited Systemic Reactions: Fever, ≥ 39˚C; Headache, Malaise, Myalgia, and Asthenia, Significant; prevents daily activity.
Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited injection site reactions (2-11 years): Pain, incapacitating, unable to perform usual activities; Erythema and Swelling, \>=5 cm. Grade 3 Solicited injection site reactions (adolescents and adults: \>=12 years): Pain, significant; prevents daily activity; Erythema and Swelling: \>10 cm. Grade 3 Solicited systemic reactions (all participants): Fever, \>=39.0°C; Headache, Malaise, Myalgia, and Asthenia: significant; prevents daily activity.
Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia.
Seropositivity against each dengue virus serotype (parental strains) was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive participants were defined as participants with neutralizing antibody titers \>=10 (1/dilution).
Seropositivity against each dengue virus serotypes (parental strains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers \>=10 (1/dilution).
Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes (parental strains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers \>=10 (1/dilution).
GMTs against each serotype with the parental dengue virus strains were assessed using a dengue PRNT assay.
GMTs against each dengue virus serotype (parental strains) were assessed using a dengue PRNT assay.
Symptomatic VCD cases were defined as acute febrile illness with fever lasting for at least 1 day (temperature \>= 37.5 degree Celsius (°C) measured at least twice with an interval of at least 4 hours), confirmed by reverse transcriptase-polymerase chain reaction and/or dengue non-structural protein-1 (NS1) enzyme-linked immunosorbent assay antigen test, and occurring more than 28 days after the third injection. Vaccine efficacy was reported as density incidence (cases/100 person-years at risk). Density incidence was defined as the number of VCD cases divided by the cumulative person-years at risk.
| Arm | Type | Description |
|---|---|---|
| CYD Dengue Vaccine + Gardasil (Concomitant Administration) | EXPERIMENTAL | Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 milliliter (mL) subcutaneously (SC) at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL Intramuscular (IM), concomitantly with the first 2 doses of CYD dengue vaccine. |
| CYD Dengue Vaccine + Gardasil (Sequential Administration) | EXPERIMENTAL | Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine. |
| CYD Dengue Vaccine + Cervarix (Concomitant Administration) | EXPERIMENTAL | Participants received 3 doses of CYD dengue vaccine 0.5 milliliter (mL) subcutaneously (SC) at Day 0, Month 6, and Month 12 and 2 doses of Cervarix vaccine 0.5 mL Intramuscularly (IM) concomitantly with the 2 first doses of CYD dengue vaccine. |
| CYD Dengue Vaccine + Cervarix (Sequential Administration) | EXPERIMENTAL | Participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13 along with the 2 doses of Cervarix vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the 2 first doses of CYD dengue vaccine. |
| CYD Dengue vaccine group | EXPERIMENTAL | Subjects will receive 3 doses of CYD dengue vaccine at 0, 6, and 12 months |
| Placebo vaccine group | PLACEBO_COMPARATOR | Subjects will receive 3 doses of placebo (NaCl, 0.9%) vaccine at 0, 6, and 12 months |
| CYD Dengue Vaccine booster Group | EXPERIMENTAL | Participants who received 3 doses of the tetravalent dengue vaccine in a previous CYD dengue vaccine study (CYD28), received a booster injection of CYD dengue vaccine at Day 0 in this study (CYD63). |
| Placebo Group | PLACEBO_COMPARATOR | Participants who received 3 doses of the tetravalent dengue vaccine in a previous CYD dengue vaccine study (CYD28), received an injection of a placebo at Day 0 in this study (CYD63). |
| STAGE-I Group 1: CYD Dengue Vaccine | EXPERIMENTAL | Participants received 3 doses of CYD dengue vaccine 0.5 milliliters (mL) subcutaneously (SC) at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3). |
| STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) | EXPERIMENTAL | Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3). |
| STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12) | EXPERIMENTAL | Participants received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3). |
| STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) | EXPERIMENTAL | Participants from Group 1 who received vaccination in STAGE-I; and were seropositive at Baseline received a booster dose of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). |
| STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) | EXPERIMENTAL | Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). |
| STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) | EXPERIMENTAL | Participants from Group 3 who received vaccination in STAGE-I and were seropositive at Baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). |
| STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) | EXPERIMENTAL | Participants from Group 1 who received vaccination in STAGE-I and were seropositive at Baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). |
| STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) | EXPERIMENTAL | Participants from Group 2 who received vaccination in STAGE-I and were seropositive at Baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). |
| STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years) | EXPERIMENTAL | Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). |
| CYD Dengue Vaccine: Group 1 | EXPERIMENTAL | Participants received 3 doses of CYD dengue vaccine, one each at 0, 2 and 6 months, respectively. |
| CYD Dengue Vaccine: Group 2 | EXPERIMENTAL | Participants received 3 doses of CYD dengue vaccine, one each at 0, 6 and 12 months, respectively. |
| CYD Dengue and JE Vaccine: Group 3 | EXPERIMENTAL | Participants received 3 doses of CYD dengue vaccine, one each at 0, 2 and 6 months, and 2 doses of JE (IXIARO) vaccine at 0 and 1 months, respectively. |
| CYD Dengue and JE Vaccine: Group 4 | EXPERIMENTAL | Participants received 2 doses of JE (IXIARO) vaccine at 0 and 1 months; and 3 doses of CYD dengue vaccine at 7, 9 and 13 months, respectively. |
| Control Vaccine Group | SHAM_COMPARATOR | - |
| Control Group | PLACEBO_COMPARATOR | Participants (Cohort 1) received rabies vaccine at Month 0 and placebo at 6 and 12 months. Participants (Cohort 2) received placebo at 0, 6, and 12 months. |
| Name | Type | Description |
|---|---|---|
| CYD Dengue Vaccine | BIOLOGICAL | 0.5 mL, SC injection at Day 0, Month 6 and 12, respectively. |
| Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant. | BIOLOGICAL | 0.5 mL, IM injection at Day 0 and Month 6, respectively. |
| Human Papillomavirus Bivalent [Types 16 and 18] Vaccine, Recombinant | BIOLOGICAL | 0.5 mL, IM at Day 0 and Month 6 |
| Placebo (NaCl 0.9%) vaccine group | BIOLOGICAL | 0.5 mL, Subcutaneous at Day 0, 6 and 12 months, respectively |
| CYD Dengue Vaccine (5 dose formulation) | BIOLOGICAL | 0.5 mL, Subcutaneous |
| Placebo, NaCl 0.9% | BIOLOGICAL | 0.5 mL, Subcutaneous |
| Placebo (Sodium chloride 0.9%) | BIOLOGICAL | 0.5 mL, Subcutaneous |
| CYD Dengue Vaccine (5-dose formulation) | BIOLOGICAL | 0.5 mL, Subcutaneous |
| Japanese Encephalitis Vaccine | BIOLOGICAL | 0.5 mL, Intramuscular |
| Tetanus Toxoid Reduced Diphtheria Toxoid Acellular Pertussis | BIOLOGICAL | NaCl: 0.5 mL, Intramuscular at Day 0 and 6 months; Adacel®: 0.5 mL, Intramuscular at 12 months |
| NaCl + influenza virus or hepatitis A vaccine | BIOLOGICAL | 0.5 mL, Subcutaneous (Intramuscular - Hepatitis A) |
| Inactivated rabies virus vaccine | BIOLOGICAL | 0.5 mL, Subcutaneous |
| Placebo | BIOLOGICAL | Sodium chloride 0.9% |
Inclusion Criteria: * Participants aged 9 to 13 years (i.e., from the day of the 9th birthday to the day prior to the 14th birthday) on the day of inclusion. * Informed consent form (ICF) or Assent form (AF) had been signed and dated by the participant (based on local regulations), and/or ICF had b...
CYD Dengue Vaccine is an investigational vaccine being developed for the prevention of dengue virus infection, including dengue fever and dengue hemorrhagic fever. It is a tetravalent vaccine designed to protect against the dengue virus. The vaccine is currently in Phase 2 clinical development and is not yet approved by regulatory authorities.
CYD Dengue Vaccine is developed by Sanofi, a multinational pharmaceutical company listed on the stock exchange under the ticker SNY. Sanofi Pasteur, the vaccines division of Sanofi, is responsible for the clinical development of this dengue vaccine candidate.
CYD Dengue Vaccine is in Phase 2 clinical development. It has completed seven clinical trials with a total enrollment of 4,002 participants. The vaccine is still investigational and has not received regulatory approval. All completed trials were randomized and sham-controlled, but none were double-blinded.
CYD Dengue Vaccine has completed seven clinical trials, including NCT00842530 in healthy children in Thailand, NCT00993447 in children and adolescents in Latin America, NCT01943825 in adults in the United States, and NCT02623725 studying a booster dose in participants who completed the 3-dose schedule. All trials are completed with no active trials ongoing.
CYD Dengue Vaccine is the investigational name for Sanofi's dengue vaccine candidate. The vaccine is also known by the brand name Dengvaxia in some markets. However, the clinical trials listed under CYD Dengue Vaccine are specifically for the tetravalent dengue vaccine developed by Sanofi Pasteur.