NCT02628444

Immunogenicity and Safety of Different Vaccination Schedules of Tetravalent Dengue Vaccine in Healthy Subjects 9 to 50 Years of Age

Completed Phase 2 Results posted Last updated 24 March 2022

What this trial tests

Phase 2 trial testing CYD Dengue Vaccine in Dengue Fever in 1,050 participants. Completed in 29 April 2020.

Timeline

2 May 2016

Primary endpoint
29 April 2020

29 April 2020

Quick facts

Lead sponsor	Sanofi Pasteur, a Sanofi Company
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	prevention
Enrollment	1,050
Start date	2 May 2016
Primary completion	29 April 2020
Estimated completion	29 April 2020
Sites	6 locations across Philippines, Colombia

Drugs / interventions tested

• CYD Dengue Vaccine — full drug profile →
• Placebo (Sodium chloride 0.9%)

Conditions studied

• Dengue Fever — all drugs for Dengue Fever →
• Dengue Hemorrhagic Fever — all drugs for Dengue Hemorrhagic Fever →

Sponsor

Sanofi Pasteur, a Sanofi Company — full company profile →

Who can join

Adults 9 to 50, any sex, with Dengue Fever or Dengue Hemorrhagic Fever. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

STAGE-I: Geometric Mean Titers (GMTs) Against Each Dengue Virus Serotype 28 Days After Last CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline Primary · 28 days after last CYD dengue vaccination

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 cri

Serotype 1

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	822	700 – 964
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	899	752 – 1075

Serotype 2

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	875	770 – 995
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	869	754 – 1002

Serotype 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	610	535 – 694
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	599	524 – 685

Serotype 4

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	531	470 – 601
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	510	453 – 575

STAGE-I: Geometric Mean Titers Against Each Dengue Virus Serotype 1 Year After Last CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline Primary · 1 year after last CYD dengue vaccination

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.

Serotype 1

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	490	398 – 604
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	504	403 – 630

Serotype 2

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	821	704 – 957
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	737	611 – 888

Serotype 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	477	405 – 561
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	437	368 – 519

Serotype 4

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	270	235 – 310
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	238	205 – 277

STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Within Group 1a and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline Primary · Group 1: 28 days post-dose 3 in STAGE-I, Group 1a: 28 days post 12 months booster dose in STAGE-II

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

Serotype 1

Group	Value	95% CI
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I	853	526 – 1384
Group 1a: CYD Dengue Vaccine-28 Days Post 12 Month Booster Dose	483	281 – 832

Serotype 2

Group	Value	95% CI
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I	1186	809 – 1738
Group 1a: CYD Dengue Vaccine-28 Days Post 12 Month Booster Dose	884	602 – 1300

Serotype 3

Group	Value	95% CI
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I	696	483 – 1002
Group 1a: CYD Dengue Vaccine-28 Days Post 12 Month Booster Dose	722	458 – 1140

Serotype 4

Group	Value	95% CI
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I	592	400 – 876
Group 1a: CYD Dengue Vaccine-28 Days Post 12 Month Booster Dose	383	269 – 545

STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Comparison Between Group 2a and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline Primary · Group 1: 28 days post-dose 3 in STAGE-I, Group 2a: 28 days post 12 months booster dose in STAGE-II

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

Serotype 1

Group	Value	95% CI
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I	875	614 – 1248
Group 2a: CYD Dengue Vaccine-28 Days Post 12 Months Booster Dose	549	331 – 911

Serotype 2

Group	Value	95% CI
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I	1023	771 – 1356
Group 2a: CYD Dengue Vaccine-28 Days Post 12 Months Booster Dose	828	569 – 1203

Serotype 3

Group	Value	95% CI
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I	568	433 – 745
Group 2a: CYD Dengue Vaccine-28 Days Post 12 Months Booster Dose	676	436 – 1049

Serotype 4

Group	Value	95% CI
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I	540	418 – 697
Group 2a: CYD Dengue Vaccine-28 Days Post 12 Months Booster Dose	270	200 – 364

STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Within Group 1b and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline Primary · Group 1: 28 days post-dose 3 in STAGE-I, Group 1b: 28 days post 24 months booster dose in STAGE-II

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 G

Serotype 1

Group	Value	95% CI
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I	1017	592 – 1746
Group 1b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose	700	401 – 1220

Serotype 2

Group	Value	95% CI
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I	838	554 – 1269
Group 1b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose	730	497 – 1071

Serotype 3

Group	Value	95% CI
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I	486	333 – 708
Group 1b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose	559	395 – 792

Serotype 4

Group	Value	95% CI
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I	556	400 – 774
Group 1b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose	364	260 – 510

STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Comparison Between Group 2b and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline Primary · Group 1: 28 days post-dose 3 in STAGE-I, Group 2b: 28 days post 24 months Booster dose in STAGE-II

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:

Serotype 1

Group	Value	95% CI
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I	875	614 – 1248
Group 2b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose	778	429 – 1414

Serotype 2

Group	Value	95% CI
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I	1023	771 – 1356
Group 2b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose	692	430 – 1116

Serotype 3

Group	Value	95% CI
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I	568	433 – 745
Group 2b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose	517	365 – 733

Serotype 4

Group	Value	95% CI
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I	540	418 – 697
Group 2b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose	379	261 – 551

STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains After CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline-Comparison Between Group 1 and Group 2 Secondary · 28 days and 1 year after last CYD dengue vaccination

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.

28 days after last vaccination: Serotype 1

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	834	713 – 975
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	877	737 – 1043

28 days after last vaccination: Serotype 2

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	879	775 – 997
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	870	758 – 1000

28 days after last vaccination: Serotype 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	620	545 – 704
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	602	529 – 686

28 days after last vaccination: Serotype 4

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	527	467 – 595
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	507	451 – 570

1 year after last vaccination: Serotype 1

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	498	406 – 611
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	512	411 – 638

1 year after last vaccination: Serotype 2

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	815	702 – 947
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	747	622 – 897

1 year after last vaccination: Serotype 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	477	407 – 558
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	444	376 – 525

1 year after last vaccination: Serotype 4

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	263	230 – 302
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	241	208 – 279

STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains in All Participants Secondary · Baseline, 28 days post vaccination 3, and 1 year post vaccination 3

GMTs of antibodies against each of the 4 dengue virus serotypes (parental strains) were assessed using the PRNT assay method.

Serotype 1: Baseline

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	131	103 – 165
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	187	147 – 237
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	198	157 – 250

Serotype 1: 28 days post vaccination 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	497	410 – 602
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	586	482 – 714
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	735	589 – 916

Serotype 1: 1 year post vaccination 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	259	200 – 336
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	279	213 – 365
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	331	252 – 435

Serotype 2: Baseline

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	172	138 – 214
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	202	163 – 252
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	181	147 – 222

Serotype 2: 28 days post vaccination 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	567	482 – 666
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	628	532 – 741
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	734	614 – 878

Serotype 2: 1 year post vaccination 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	470	380 – 582
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	457	364 – 574
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	500	402 – 623

Serotype 3: Baseline

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	163	131 – 202
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	180	145 – 222
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	169	138 – 207

Serotype 3: 28 days post vaccination 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	432	373 – 500
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	446	383 – 519
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	505	428 – 595

STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains (by Baseline Dengue Status) in Participants Who Were Seropositive and Seronegative at Baseline Secondary · Baseline, 28 days post vaccination 3, and 1 year post vaccination 3

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. Dengue seronegative participants at Baseline were defined as the participants with valid titer \<0 (1/dilution) for all serotypes with parental dengue virus strains.

Seropositive- Serotype 1: Baseline

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	239	194 – 295
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	304	244 – 379
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	328	267 – 404

Seropositive- Serotype 1: 28 days post vaccination 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	834	713 – 975
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	877	737 – 1043
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	1201	1007 – 1431

Seropositive- Serotype 1: 1 year post vaccination 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	498	406 – 611
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	512	411 – 638
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	618	500 – 764

Seropositive- Serotype 2: Baseline

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	331	279 – 394
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	326	271 – 393
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	293	247 – 347

Seropositive- Serotype 2: 28 days post vaccination 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	879	775 – 997
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	870	758 – 1000
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	1046	912 – 1201

Seropositive- Serotype 2: 1 year post vaccination 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	815	702 – 947
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	747	622 – 897
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	798	676 – 942

Seropositive- Serotype 3: Baseline

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	310	263 – 367
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	290	241 – 349
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	269	227 – 319

Seropositive- Serotype 3: 28 days post vaccination 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	620	545 – 704
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	602	529 – 686
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	694	604 – 797

STAGE-II: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains After Booster CYD Dengue Vaccination in Participants Seropositive at Baseline Secondary · Baseline, 28 days post vaccination-3, and 28 days post booster dose

GMTs of antibodies against each of the 4 dengue virus serotype (1, 2, 3, or 4) were assessed using the PRNT assay. 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. Titers were measured in terms of 1/dilution.

Serotype 1: Baseline

Group	Value	95% CI
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	246	183 – 331
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	283	207 – 385
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	309	227 – 421
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	231	171 – 313
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	327	239 – 447
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	350	265 – 462

Serotype 1: 28 days post vaccination 3

Group	Value	95% CI
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	828	671 – 1022
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	933	730 – 1192
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	1111	868 – 1423
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	840	664 – 1061
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	824	644 – 1056
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	1301	1011 – 1675

Serotype 1 : 28 days post booster dose

Group	Value	95% CI
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	505	335 – 763
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	552	375 – 812
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	861	572 – 1297
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	707	472 – 1057
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	749	465 – 1207
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	1199	755 – 1902

Serotype 2 : Baseline

Group	Value	95% CI
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	370	295 – 466
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	335	258 – 437
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	283	221 – 363
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	296	228 – 385
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	318	244 – 413
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	303	241 – 382

Serotype 2 : 28 days post vaccination 3

Group	Value	95% CI
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	986	834 – 1166
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	897	735 – 1096
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	1018	850 – 1218
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	783	648 – 947
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	844	695 – 1025
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	1077	871 – 1331

Serotype 2 : 28 days post booster dose

Group	Value	95% CI
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	856	638 – 1147
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	858	639 – 1152
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	867	640 – 1174
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	813	600 – 1100
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	655	461 – 931
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	967	697 – 1343

Serotype 3 : Baseline

Group	Value	95% CI
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	363	285 – 462
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	399	308 – 519
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	287	222 – 371
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	266	211 – 335
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	210	164 – 271
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	253	201 – 317

Serotype 3: 28 days post vaccination 3

Group	Value	95% CI
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	733	617 – 871
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	659	547 – 794
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	725	607 – 865
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	524	434 – 631
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	551	459 – 661
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	663	534 – 823

STAGE-I: Percentage of Participants With Antibodies Titer >=10 (1/Dilution) Against Each Serotype With the Parental Dengue Virus Strains in All Participants Secondary · Baseline, 28 days post vaccination 3, and 1 year post vaccination 3

GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay.

Serotype 1: Baseline

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	77.8	72.9 – 82.1
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	80.5	75.8 – 84.6
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	83.4	79.0 – 87.3

Serotype 1: 28 days post vaccination 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	96.3	93.7 – 98.1
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	97.2	94.8 – 98.7
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	94.1	91.0 – 96.4

Serotype 1: 1 year post vaccination 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	88.3	83.5 – 92.2
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	87.5	82.5 – 91.5
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	88.3	83.4 – 92.1

Serotype 2: Baseline

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	82.6	78.1 – 86.5
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	83.8	79.4 – 87.7
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	85.2	81.0 – 88.9

Serotype 2: 28 days post vaccination 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	98.2	96.0 – 99.3
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	96.6	94.0 – 98.3
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	96.0	93.2 – 97.8

Serotype 2: 1 year post vaccination 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	95.7	92.2 – 97.9
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	94.4	90.6 – 97.0
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	94.8	91.1 – 97.3

Serotype 3: Baseline

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	82.6	78.1 – 86.5
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	84.1	79.7 – 87.9
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	87.0	83.0 – 90.5

Serotype 3: 28 days post vaccination 3

Group	Value	95% CI
STAGE-I Group 1: CYD Dengue Vaccine	98.5	96.5 – 99.5
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	98.1	96.0 – 99.3
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	97.5	95.2 – 98.9

STAGE-II: Percentage of Participants With Antibodies Titer >=10 (1/Dilution) Against Each Serotype With the Parental Dengue Virus Strain in Participants Seropositive at Baseline Secondary · Baseline, 28 days post vaccination 3, and 1 year post vaccination 3

GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. 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.

Serotype 1: Baseline

Group	Value	95% CI
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	92.2	86.5 – 96.0
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	90.3	84.2 – 94.6
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	91.8	86.2 – 95.7
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	92.1	86.4 – 96.0
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	91.7	85.9 – 95.6
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	97.2	93.0 – 99.2

Serotype 1: 28 days post vaccination 3

Group	Value	95% CI
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	100.0	97.3 – 100.0
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	99.3	96.1 – 100.0
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	100.0	97.5 – 100.0
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	99.3	96.0 – 100.0
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	99.3	96.1 – 100.0
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	100.0	97.4 – 100.0

Serotype 1 : 1 year post vaccination 3

Group	Value	95% CI
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	100.0	97.3 – 100.0
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	99.3	96.0 – 100.0
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	99.3	96.2 – 100.0
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	100.0	97.2 – 100.0
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	96.9	92.3 – 99.2
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	98.5	94.6 – 99.8

Serotype 2: Baseline

Group	Value	95% CI
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	99.3	96.1 – 100.0
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	94.4	89.3 – 97.6
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	94.6	89.6 – 97.6
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	96.4	91.9 – 98.8
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	94.4	89.3 – 97.6
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	97.2	93.0 – 99.2

Serotype 2 : 28 days post vaccination 3

Group	Value	95% CI
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	100.0	97.3 – 100.0
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	99.3	96.1 – 100.0
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	100.0	97.5 – 100.0
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	100.0	97.3 – 100.0
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	99.3	96.1 – 100.0
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	100.0	97.4 – 100.0

Serotype 2 : 1 year post vaccination 3

Group	Value	95% CI
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	100.0	97.3 – 100.0
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	99.3	96.0 – 100.0
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	100.0	97.5 – 100.0
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	100.0	97.2 – 100.0
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	98.5	94.6 – 99.8
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	100.0	97.2 – 100.0

Serotype 3: Baseline

Group	Value	95% CI
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	98.6	95.0 – 99.8
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	96.5	92.1 – 98.9
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	95.2	90.4 – 98.1
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	97.1	92.8 – 99.2
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	93.1	87.6 – 96.6
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	100.0	97.5 – 100.0

Serotype 3: 28 days post vaccination

Group	Value	95% CI
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	100.0	97.3 – 100.0
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	100.0	97.4 – 100.0
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	100.0	97.5 – 100.0
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	99.3	96.0 – 100.0
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	100.0	97.4 – 100.0
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	100.0	97.4 – 100.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Unsolicited non-serious AEs: Day 0 to Day 28 post any vaccination SR: within 7 & 14 days post any vaccination; SAE: up to 24 months for STAGE-I); up to 6 months after last vaccination for Stage-2 (i.e., up to 30 months [for Groups 1a, 2a, and 3a]; & up to 42 months [for Groups 1b, 2b, and 3b]). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

STAGE-I Group 1: CYD Dengue Vaccine

Serious: 14/348 (4%)

Deaths: 0/348

STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)

Serious: 26/348 (7%)

Deaths: 1/348

STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)

Serious: 18/352 (5%)

Deaths: 1/352

STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)

Serious: 3/55 (5%)

Deaths: 0/55

STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)

Serious: 2/53 (4%)

Deaths: 0/53

STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)

Serious: 0/59 (0%)

Deaths: 0/59

STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)

Serious: 0/56 (0%)

Deaths: 0/56

STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)

Serious: 2/62 (3%)

Deaths: 0/62

STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)

Serious: 1/53 (2%)

Deaths: 0/53

Serious adverse events (51 terms)

Reaction	System	STAGE-I Group 1: CYD Dengu…	STAGE-I Group 2: Placebo +…	STAGE-I Group 3: Placebo +…	STAGE-II Group 1a: CYD Vac…	STAGE-II Group 1b: CYD Vac…	STAGE-II Group 2a: Placebo…	STAGE-II Group 2b: Placebo…	STAGE-II Group 3a: Placebo…	STAGE-II Group 3b: Placebo…
Appendicitis	Infections and infestations	—	—	—	—	—	—	—	—	—
Abortion Spontaneous	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—	—	—	—
Myocardial Infarction	Cardiac disorders	—	—	—	—	—	—	—	—	—
Branchial Cyst	Congenital, familial and genetic disorders	—	—	—	—	—	—	—	—	—
Thyroid Cyst	Endocrine disorders	—	—	—	—	—	—	—	—	—
Food Poisoning	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—
Food Allergy	Immune system disorders	—	—	—	—	—	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—	—	—	—	—	—
Diarrhoea Infectious	Infections and infestations	—	—	—	—	—	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—	—	—	—	—	—
Groin Abscess	Infections and infestations	—	—	—	—	—	—	—	—	—
Hepatitis A	Infections and infestations	—	—	—	—	—	—	—	—	—
Orchitis	Infections and infestations	—	—	—	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—	—	—	—
Pneumonia Staphylococcal	Infections and infestations	—	—	—	—	—	—	—	—	—
Urinary Tract Infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Viral Infection	Infections and infestations	—	—	—	—	—	—	—	—	—
Animal Bite	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—
Forearm Fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—
Gun Shot Wound	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—
Head Injury	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—
Jaw Fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—
Radius Fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—
Road Traffic Accident	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—
Thermal Burn	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—

Other adverse events (6 terms — click to expand)

Reaction	System	STAGE-I Group 1: CYD Dengu…	STAGE-I Group 2: Placebo +…	STAGE-I Group 3: Placebo +…	STAGE-II Group 1a: CYD Vac…	STAGE-II Group 1b: CYD Vac…	STAGE-II Group 2a: Placebo…	STAGE-II Group 2b: Placebo…	STAGE-II Group 3a: Placebo…	STAGE-II Group 3b: Placebo…
Headache	Nervous system disorders	—	—	—	—	—	—	—	—	—
Injection Site Pain	General disorders	—	—	—	—	—	—	—	—	—
Malaise	General disorders	—	—	—	—	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—	—	—	—
Fever	General disorders	—	—	—	—	—	—	—	—	—

Most-reported serious reactions: Appendicitis, Abortion Spontaneous, Myocardial Infarction, Branchial Cyst, Thyroid Cyst, Food Poisoning, Food Allergy, Cellulitis.

Data from ClinicalTrials.gov NCT02628444 adverse events section.

Sponsor's own description

The aim of the study was to assess the immune response and the safety of different vaccination schedules of CYD dengue vaccine.

The primary objectives of the study were:

* To demonstrate the non-inferiority of the immune response elicited against each dengue serotype by CYD dengue vaccine given as a 2-dose schedule (Group 2) compared to the immune response elicited by CYD dengue vaccine given as a 3-dose schedule (Group 1), in previously dengue exposed participants 28 days after the last injection.
* To demonstrate the non-inferiority of the immune response elicited against each dengue serotype by CYD dengue vaccine given as a 2-dose schedule (Group 2) compared to the immune response elicited by CYD vaccine given as a 3-dose schedule (Group 1) in previously dengue exposed participants, 1 year after the last injection.
* To demonstrate the non-inferiority of the immune response elicited against each dengue serotype elicited by a booster dose of CYD dengue vaccine one year or two years after the last injection in the primary series in previously dengue exposed participants, compared to the immune response post dose 3 in Group 1.

The secondary objectives of the study were:

* To demonstrate the superiority of the immune response elicited by CYD dengue vaccine given as a 2-dose schedule (Group 2) compared to the immune response elicited by CYD dengue vaccine given as a 3-dose schedule (Group 1), in previously dengue exposed participants, 28 days after the last injection.
* To demonstrate the superiority of the immune response elicited by CYD dengue vaccine given as a 2-dose schedule (Group 2) compared to the immune response elicited by CYD dengue vaccine given as a 3-dose schedule (Group 1), in previously dengue exposed participants, one year after the last injection.
* To describe the neutralizing antibody levels of each dengue serotype at 28 days post-injection 3 to the antibody levels immediately before receiving a booster dose, by baseline dengue serostatus.
* To describe the neutralizing antibody levels of each dengue serotype at 28 days post-injection 2 and 28 days post-injection 3 from Group 1 in a primary series schedule by baseline dengue serostatus.
* To demonstrate the superiority of the immune response elicited against each dengue serotype 28 days after administration of a booster dose of CYD dengue vaccine, in previously dengue exposed participants, at one year or two years after last injection in the primary series.
* To describe the seroconversion rate 28 days post-booster injection in all 3 groups.
* To describe all hospitalized virologically confirmed dengue (VCD) cases during the study.
* To evaluate the safety profile of CYD after each and any injection during the trial. Safety assessments include solicited reactions within 7 or 14 days after each injection, unsolicited adverse events within 28 days after each injection, and serious adverse events during the study period.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. A review of Dengvaxia®: development to deployment.
   Thomas SJ, Yoon IK. · · 2019 · cited 223× · PMID 31589551 · DOI 10.1080/21645515.2019.1658503
2. Immunogenicity and safety of simplified vaccination schedules for the CYD-TDV dengue vaccine in healthy individuals aged 9-50 years (CYD65): a randomised, controlled, phase 2, non-inferiority study.
   Coronel-MartÍnez DL, Park J, López-Medina E, Capeding MR, et al · · 2021 · cited 17× · PMID 33212067 · DOI 10.1016/s1473-3099(20)30767-2
3. Immunogenicity and safety of a dengue vaccine given as a booster in Singapore: a randomized Phase II, placebo-controlled trial evaluating its effects 5-6 years after completion of the primary series.
   Park J, Archuleta S, Oh MH, Shek LP, et al · · 2020 · cited 8× · PMID 31464558 · DOI 10.1080/21645515.2019.1661204
4. Immunogenicity and safety of booster CYD-TDV dengue vaccine after alternative primary vaccination schedules in healthy individuals aged 9-50 years: a randomised, controlled, phase 2, non-inferiority study.
   Coronel-Martinez DL, Park J, López-Medina E, Capeding MR, et al · · 2022 · cited 6× · PMID 35364022 · DOI 10.1016/s1473-3099(21)00706-4
5. Immunobridging efficacy of a tetravalent dengue vaccine against dengue and against hospitalized dengue from children/adolescents to adults in highly endemic countries.
   Huang Y, Moodie Z, Juraska M, Fong Y, et al · · 2021 · cited 3× · PMID 33369671 · DOI 10.1093/trstmh/traa154