CLINICAL EFFICACY AND SAFETY OF A

NOVEL TETRAVALENT DENGUE VACCINE

IN HEALTHY CHILDREN IN ASIA: A PHASE
3, RANDOMISED, OBSERVER-MASKED,
PLACEBO-CONTROLLED TRIAL
ABDULLAH ICHSAN
1301 1214 0661

Maria Rosario Capeding, Ngoc Huu Tran, Sri Rezeki S Hadinegoro,

Hussain Imam HJ Muhammad Ismail, Tawee Chotpitayasunondh,
Mary Noreen Chua, Chan Quang Luong, Kusnandi Rusmil, Dewa
Nyoman Wirawan, Revathy Nallusamy, Punnee Pitisuttithum, Usa
Thisyakorn, In-Kyu Yoon, Diane van der Vliet, Edith Langevin, Thelma
Laot, Yanee Hutagalung, Carina Frago, Mark Boaz, T Anh Wartel,
Nadia G Tornieporth, Melanie Saville, Alain Bouckenooghe, and the
CYD14 Study Group*

An estimated 390 million dengue

infections take place every year

Introductions

About 70% of the overall disease

burden, which has increased by 30
times in the past 50 years, is
reported in the Asia-Pacic region
The vaccine candidate assessed here
is a recombinant, live, attenuated,
tetravalent dengue vaccine (CYD-TDV)

Assess the ecacy of the dengue vaccine

against symptomatic, virologically
conrmed dengue (VCD), irrespective of
serotype or disease severity.

Research aim

 Multicentre, randomised, observer-masked, placebo-controlled,

phase 3 trial in ve countries in the Asia-Pacic (3 centres in
Indonesia, 2 centres in Malaysia, 2 centres in the Philippines, 3
centres in Thailand, and 2 centres in Vietnam).
INCLUSSION CRITERIA:
Enrolled healthy children aged 214 years, whose parents or
guardians were intending to stay in the trials catchment area for
the duration of the trial.
EXCLUSSION CRITERIA
Excluded children with acute febrile illness (until resolution), those
who had received another vaccine (until 4 weeks after
vaccination), those with congenital or acquired immunode ciency,
or those with other criteria listed in the protocol.

Methods

 Eligible children were randomly assigned (2:1), by computer-generated

permuted blocks of six, to receive CYD-TDV or placebo.
The randomisation list was generated with stratication by site and age
(25 years, 611 years, and 1214 years).
A observer-masked design was needed because the physical
appearance of the vaccine and placebo diered.
The unmasked trial sta , who were responsible specically for the
preparation and administration of injections, were not included in the
follow-up of the participants.
Study investigators and parents and guardians will remain masked until
the hospital phase of the trial has been completed

Methods

 All participants attended ve visits at months 0, 6, and 12 for

vaccination and months 13 and 25 for followup; at month 18
participants had a follow-up phone call or home visit. Blood
samples were taken from all participants at month 13.
Children are actively monitored via weekly contact with parents
and guardians or participants, and by surveillance of school
absenteeism.
Active surveillance started on the day of administration of dose
one and continued until month 25.
Documented and assessed all serious adverse events that took
place at any time during the trial.

Methods

Methods

 250 cases of virologically conrmed dengue took place more than

28 days after the third injection
(117 [47%] in the vaccine group and 133 [53%] in the control
group).
The primary endpoint was achieved with 56,5 % (95 % CI 43,8
66,4) ecacy.
Recorded 647 serious adverse events
(402 [62%] in the vaccine group and 245 [38%] in the control
group).
54 (1%) children in the vaccine group and 33 (1%) of those in the
control group had serious adverse events that happened within 28
days of vaccination.

Findings

Dengue vaccine is ecacious when

given as 3 injections at months
0, 6, and 12 to children aged 214
years in endemic areas in Asia,
and has a good safety prole.

Interpretation

 Notably, almost 99% of participants who received at least one

injection went on to receive all 3 injections; we could not assess
ecacy after only one or 2 doses.
Vaccine ecacy was higher for participants who were seropositive
for dengue than for those who were seronegative. Furthermore,
vaccine e cacy increased with age. However, ecacy was similar
across the ve countries.
Predictive models for vaccine ecacy, including population and
epidemiological characteristics, might be needed to guide vaccine
implementation in dierent settings around the world.

Discussions

 CONSISTENT WITH PREVIOUS STUDIES,

the safety prole was good after more than 2 years of follow-up.
Will continue to follow the trial population for safety for 5 years
after the third vaccination in the hospital-based phase of our study.

In summary, this trial was successfully done over

more than 2 years in diverse dengue-endemic
areas in Asia, a region that accounts for 70% of the
global dengue burden.

Discussions

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