Trial Outcomes & Findings for Safety and Immunogenicity Study of V503 (GARDASIL™9, 9vHPV Vaccine) Administered to 9- to 26-Year-Old Females and Males in Vietnam (V503-017) (NCT NCT03546842)

Results Overview

Seroconversion was defined as a participant who was anti-HPV seronegative at Day 1 and became seropositive at 4 weeks postdose 3 (Month 7). Anti-HPV antibodies were measured using a Competitive Luminex Immunoassay.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

201 participants

Primary outcome timeframe

4 weeks postdose 3 (Month 7)

Results posted on

2020-02-25

Participant Flow

Participant milestones

Participant milestones
Measure	9vHPV Vaccine Participants received a single 0.5-mL intramuscular injection of the 9-valent human papillomavirus (9vHPV) vaccine at Day 1, Month 2, and Month 6
Overall Study STARTED	201
Overall Study Vaccination 1	200
Overall Study Vaccination 2	200
Overall Study Vaccination 3	198
Overall Study COMPLETED	198
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	9vHPV Vaccine Participants received a single 0.5-mL intramuscular injection of the 9-valent human papillomavirus (9vHPV) vaccine at Day 1, Month 2, and Month 6
Overall Study Protocol Violation	1
Overall Study Withdrawal by Subject	2

Baseline Characteristics

Safety and Immunogenicity Study of V503 (GARDASIL™9, 9vHPV Vaccine) Administered to 9- to 26-Year-Old Females and Males in Vietnam (V503-017)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	9vHPV Vaccine n=201 Participants Participants received a single 0.5-mL intramuscular injection of the 9vHPV vaccine at Day 1, Month 2, and Month 6
Age, Continuous	15.8 years STANDARD_DEVIATION 4.4 • n=5 Participants
Sex: Female, Male Female	135 Participants n=5 Participants
Sex: Female, Male Male	66 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	201 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	201 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 weeks postdose 3 (Month 7)

Population: All allocated participants who were seronegative to the appropriate HPV type at Day 1, received all 3 vaccinations with the correct dose within acceptable day ranges, provided a serum sample within 21 to 49 days postdose 3, and had no protocol deviations that could interfere with the evaluation of participant's immune response to 9vHPV vaccination.

Seroconversion was defined as a participant who was anti-HPV seronegative at Day 1 and became seropositive at 4 weeks postdose 3 (Month 7). Anti-HPV antibodies were measured using a Competitive Luminex Immunoassay.

Outcome measures

Outcome measures
Measure	9vHPV Vaccine n=195 Participants Participants received a single 0.5-mL intramuscular injection of the 9vHPV vaccine at Day 1, Month 2, and Month 6
Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 Anti-HPV 6	100 Percentage of Participants Interval 98.1 to 100.0
Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 Anti-HPV 11	100 Percentage of Participants Interval 98.1 to 100.0
Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 Anti-HPV 16	100 Percentage of Participants Interval 98.0 to 100.0
Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 Anti-HPV 18	100.0 Percentage of Participants Interval 98.1 to 100.0
Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 Anti-HPV 31	100.0 Percentage of Participants Interval 98.1 to 100.0
Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 Anti-HPV 33	100.0 Percentage of Participants Interval 98.1 to 100.0
Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 Anti-HPV 45	100.0 Percentage of Participants Interval 98.1 to 100.0
Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 Anti-HPV 52	100.0 Percentage of Participants Interval 98.1 to 100.0
Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 Anti-HPV 58	100.0 Percentage of Participants Interval 98.1 to 100.0

SECONDARY outcome

Timeframe: Up to 5 days after any vaccination

Population: All participants that received at least 1 vaccination with 9vHPV vaccine and provided safety data at any time during the study.

An adverse event (AE) was defined as any untoward medical occurrence in a participant which did not necessarily have a causal relationship with study vaccine. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the study vaccine or protocol-specified procedure was also an AE. The participant or the parent/guardian of the participant were to record the presence of any vaccination report card (VRC)-prompted injection-site AEs that occurred in the 5 days after any vaccination. The percentage of participants with an injection-site AE prompted on the VRC (erythema, pain, and swelling) was summarized.

Outcome measures

Outcome measures
Measure	9vHPV Vaccine n=200 Participants Participants received a single 0.5-mL intramuscular injection of the 9vHPV vaccine at Day 1, Month 2, and Month 6
Percentage of Participants With a Solicited Injection-site Adverse Event	45.0 Percentage of Participants Interval 38.0 to 52.2

SECONDARY outcome

Timeframe: Up to 5 days after any vaccination

Population: All participants that received at least 1 vaccination with 9vHPV vaccine and provided safety data at any time during the study.

An AE was defined as any untoward medical occurrence in a participant which did not necessarily have a causal relationship with study vaccine. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the study vaccine or protocol-specified procedure was also an AE. The only solicited systemic AE was in response to results of daily oral temperature assessments. The participant or the parent/guardian of the participant will be asked to record the participant's oral temperature in the evening after each study vaccination and daily for 4 days after each study vaccination on VRC. The percentage of participants that had an AE due to an elevated oral temperature \[(≥ 37.8 °C (100.0 °F)\] was summarized.

Outcome measures

Outcome measures
Measure	9vHPV Vaccine n=200 Participants Participants received a single 0.5-mL intramuscular injection of the 9vHPV vaccine at Day 1, Month 2, and Month 6
Percentage of Participants With a Solicited Systemic Adverse Event	0.0 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 4 weeks postdose 3 (Month 7)

Population: All participants that received at least 1 vaccination with 9vHPV vaccine and provided safety data at any time during the study.

A serious adverse event (SAE) is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. The percentage of participants that experience at least one SAE that was reported as at least possibly related to the study vaccine was summarized.

Outcome measures

Outcome measures
Measure	9vHPV Vaccine n=200 Participants Participants received a single 0.5-mL intramuscular injection of the 9vHPV vaccine at Day 1, Month 2, and Month 6
Percentage of Participants With a Vaccine-related Serious Adverse Event	0.0 Percentage of Participants

SECONDARY outcome

Timeframe: Day 1 (predose)

Population: All allocated participants who were seronegative to the appropriate HPV type at Day 1, received all 3 vaccinations with the correct dose within acceptable day ranges, provided a serum sample within 21 to 49 days postdose 3, and had no protocol deviations that could interfere with the evaluation of participant's immune response to 9vHPV vaccination.

Anti-HPV Type 6, 11, 16, 18, 31, 33, 45, 52, and 58 antibodies are measured using a Competitive Luminex Immunoassay. Titers are reported in milli Merck units/mL (mMU/mL).

Outcome measures

Outcome measures
Measure	9vHPV Vaccine n=195 Participants Participants received a single 0.5-mL intramuscular injection of the 9vHPV vaccine at Day 1, Month 2, and Month 6
Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 Anti-HPV 6	NA mMU/mL \< Lower Limit of Quantification (LLOQ) of 20 mMU/mL
Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 Anti-HPV 11	NA mMU/mL \< LLOQ of 16 mMU/mL
Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 Anti-HPV 16	NA mMU/mL \< LLOQ of 20 mMU/mL
Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 Anti-HPV 18	29.3 mMU/mL Interval 27.7 to 31.1
Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 Anti-HPV 31	NA mMU/mL \< LLOQ of 10 mMU/mL
Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 Anti-HPV 33	NA mMU/mL Interval to 8.3 \< LLOQ of 8 mMU/mL
Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 Anti-HPV 45	NA mMU/mL \< LLOQ of 8 mMU/mL
Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 Anti-HPV 52	NA mMU/mL \< LLOQ of 8 mMU/mL
Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 Anti-HPV 58	NA mMU/mL \< LLOQ of 8 mMU/mL

SECONDARY outcome

Timeframe: 4 weeks postdose 3 (Month 7)

Population: All allocated participants who were seronegative to the appropriate HPV type at Day 1, received all 3 vaccinations with the correct dose within acceptable day ranges, provided a serum sample within 21 to 49 days postdose 3, and had no protocol deviations that could interfere with the evaluation of participant's immune response to 9vHPV vaccination.

Anti-HPV Type 6, 11, 16, 18, 31, 33, 45, 52, and 58 antibodies are measured using a Competitive Luminex Immunoassay. Titers are reported in mMU/mL.

Outcome measures

Outcome measures
Measure	9vHPV Vaccine n=195 Participants Participants received a single 0.5-mL intramuscular injection of the 9vHPV vaccine at Day 1, Month 2, and Month 6
Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 Anti-HPV 6	1008.2 mMU/mL Interval 921.9 to 1102.6
Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 Anti-HPV 11	796.3 mMU/mL Interval 722.2 to 878.0
Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 Anti-HPV 16	4605.4 mMU/mL Interval 4163.7 to 5093.9
Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 Anti-HPV 18	1621.6 mMU/mL Interval 1441.2 to 1824.5
Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 Anti-HPV 31	1137.9 mMU/mL Interval 1017.2 to 1273.0
Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 Anti-HPV 33	507.8 mMU/mL Interval 458.5 to 562.4
Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 Anti-HPV 45	579.2 mMU/mL Interval 511.7 to 655.6
Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 Anti-HPV 52	500.8 mMU/mL Interval 450.5 to 556.7
Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 Anti-HPV 58	701.8 mMU/mL Interval 628.5 to 783.7

Adverse Events

9vHPV Vaccine

Serious events: 1 serious events

Other events: 90 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	9vHPV Vaccine n=200 participants at risk Participants received a single 0.5-mL intramuscular injection of the 9vHPV vaccine at Day 1, Month 2, and Month 6
Infections and infestations Subcutaneous abscess	0.50% 1/200 • Number of events 1 • Up to 4 weeks postdose 3 (Month 7) Population for All-cause mortality included all enrolled participants. Population for Non-serious adverse events and serious adverse events included all participants that received at least 1 vaccination with 9vHPV vaccine and provided safety data at any time during the study.

Other adverse events

Other adverse events
Measure	9vHPV Vaccine n=200 participants at risk Participants received a single 0.5-mL intramuscular injection of the 9vHPV vaccine at Day 1, Month 2, and Month 6
General disorders Injection site pain	44.5% 89/200 • Number of events 138 • Up to 4 weeks postdose 3 (Month 7) Population for All-cause mortality included all enrolled participants. Population for Non-serious adverse events and serious adverse events included all participants that received at least 1 vaccination with 9vHPV vaccine and provided safety data at any time during the study.
General disorders Injection site swelling	6.0% 12/200 • Number of events 16 • Up to 4 weeks postdose 3 (Month 7) Population for All-cause mortality included all enrolled participants. Population for Non-serious adverse events and serious adverse events included all participants that received at least 1 vaccination with 9vHPV vaccine and provided safety data at any time during the study.

Additional Information

Clinical Trials Disclosure

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If publication activity is not directed by the sponsor, the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission. This allows the sponsor to protect proprietary information and to provide comments.
Publication restrictions are in place

Restriction type: OTHER