Trial Outcomes & Findings for Safety and Tolerability Study of V501 in Japanese Boys (V501-200) (NCT NCT02576054)

NCT ID: NCT02576054

Last Updated: 2019-11-25

Results Overview

Antibodies to HPV Types 6, 11, 16, and 18 were measured using a competitive luminex immunoassay 4 weeks after 3rd vaccination (Month 7). Antibody titers were expressed as milli Merck units/mL (mMU/mL). Seroconversion was defined as an anti-HPV 6 titer ≥20 mMU/mL, an anti-HPV 11 titer ≥16 mMU/mL, an anti-HPV 16 titer of ≥20 mMU/mL and an anti-HPV 18 titer of ≥24 mMU/mL.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 101 participants
• Primary outcome timeframe: Four weeks postdose 3 (Month 7)
• Results posted on: 2019-11-25

Participant Flow

Participant milestones

Measure	V501 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6
Overall Study STARTED	101
Overall Study Vaccination 1	100
Overall Study Vaccination 2	100
Overall Study Vaccination 3	100
Overall Study COMPLETED	100
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	V501 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Safety and Tolerability Study of V501 in Japanese Boys (V501-200)

Baseline characteristics by cohort

Measure	V501 n=101 Participants 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6
Age, Continuous	12.2 years STANDARD_DEVIATION 2.0 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	101 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	101 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	101 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: Four weeks postdose 3 (Month 7)

Population: All participants that received all 3 vaccinations within acceptable day ranges, were seronegative to the relevant HPV type at Day 1, did not have protocol violations that could interfere with evaluation of the immune response, and provided Month 7 serology result within 21 to 49 days post dose 3.

Antibodies to HPV Types 6, 11, 16, and 18 were measured using a competitive luminex immunoassay 4 weeks after 3rd vaccination (Month 7). Antibody titers were expressed as milli Merck units/mL (mMU/mL). Seroconversion was defined as an anti-HPV 6 titer ≥20 mMU/mL, an anti-HPV 11 titer ≥16 mMU/mL, an anti-HPV 16 titer of ≥20 mMU/mL and an anti-HPV 18 titer of ≥24 mMU/mL.

Outcome measures

Measure	V501 n=99 Participants 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6	Participants Aged 16 to 26 Years (PN122) 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6
Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18 Anti HPV 6	94.9 Percentage of Participants Interval 88.5 to 98.3	—
Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18 Anti HPV 11	99.0 Percentage of Participants Interval 94.4 to 100.0	—
Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18 Anti HPV 16	99.0 Percentage of Participants Interval 94.5 to 100.0	—
Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18 Anti HPV 18	99.0 Percentage of Participants Interval 94.4 to 100.0	—

PRIMARY outcome

Timeframe: Up to Day 5 after any vaccination

Population: All participants who received at least 1 study vaccination and had follow-up safety data.

The parent/guardian of the participant was to record the participant's oral temperature in the evening after each study vaccination and daily for 4 days after each study vaccination. Elevated temperature was defined as ≥99.5°F (≥37.5ºC). The percentage of participants that had an elevated temperature was summarized.

Outcome measures

Measure	V501 n=100 Participants 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6	Participants Aged 16 to 26 Years (PN122) 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6
Percentage of Participants With Elevated Oral Temperature (>=37.5° C) ≥ 38.5 °C (101.3 °F)	2.0 Percentage of Participants	—
Percentage of Participants With Elevated Oral Temperature (>=37.5° C) ≥ 37.5 °C (99.5 °F) and < 38.0 °C (100.4 °F)	3.0 Percentage of Participants	—
Percentage of Participants With Elevated Oral Temperature (>=37.5° C) ≥ 38.0 °C (100.4 °F) and < 38.5 °C (101.3 °F)	1.0 Percentage of Participants	—

PRIMARY outcome

Timeframe: Up to Day 5 after any vaccination

Population: All participants who received at least 1 study vaccination and had follow-up safety data.

An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study drug. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug or a protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study drug or protocol-specified procedure is also an AE. The parent/guardian of the participant was 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

Measure	V501 n=100 Participants 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6	Participants Aged 16 to 26 Years (PN122) 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6
Percentage of Participants With an Injection-site Adverse Event	64.0 Percentage of Participants	—

PRIMARY outcome

Timeframe: Up to Day 15 after any vaccination

Population: All participants who received at least 1 study vaccination and had follow-up safety data.

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

Outcome measures

Measure	V501 n=100 Participants 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6	Participants Aged 16 to 26 Years (PN122) 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6
Percentage of Participants With a Systemic Adverse Event	21.0 Percentage of Participants	—

PRIMARY outcome

Timeframe: Up to Day 15 after any vaccination

Population: All participants who received at least 1 study vaccination and had follow-up safety data.

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, is a cancer, is an overdose, or is another important medical event. The percentage of participants that experienced 1 or more SAEs was summarized.

Outcome measures

Measure	V501 n=100 Participants 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6	Participants Aged 16 to 26 Years (PN122) 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6
Percentage of Participants With a Serious Adverse Event	0.0 Percentage of Participants	—

PRIMARY outcome

Timeframe: Up to 30 months

Population: All participants who received at least 1 study vaccination and had follow-up safety data.

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, is a cancer, is an overdose, or is another important medical event. The percentage of participants that experienced 1 or more SAEs that were considered at least possibly related to the study vaccine was summarized.

Outcome measures

Measure	V501 n=100 Participants 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6	Participants Aged 16 to 26 Years (PN122) 0.5 mL intramuscular injection on 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: Four weeks postdose 3 (Month 7)

Population: Participants 9 to 15 years old (PN200) or 16 to 26 years old (PN122) that received all 3 vaccinations within acceptable day ranges, were seronegative to the relevant HPV type at Day 1, did not have protocol violations that could interfere with evaluation of the immune response, and provided Month 7 serology result within 21 to 49 days post dose 3.

Antibodies to HPV Types 6, 11, 16, and 18 were measured using a competitive luminex immunoassay. Antibody titers were expressed mMU/mL. GMTs obtained for each anti-HPV from this study were compared to each of the ant-HPV GMTs obtained in study V501-122 (NCT NCT01862874) in which Japanese males 16 to 26 years received V501 in the same 3 dose regimen, to test a hypothesis that would demonstrate non-inferiority.

Outcome measures

Measure	V501 n=99 Participants 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6	Participants Aged 16 to 26 Years (PN122) n=487 Participants 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6
Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18 Participants Aged 9 to 15 Years Versus Participants Aged 16 to 26 Years Anti-HPV 6	482.9 mMU/mL Interval 351.1 to 664.1	385.0 mMU/mL Interval 355.7 to 416.7
Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18 Participants Aged 9 to 15 Years Versus Participants Aged 16 to 26 Years Anti-HPV 11	1052.8 mMU/mL Interval 851.3 to 1302.0	458.4 mMU/mL Interval 424.8 to 494.7
Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18 Participants Aged 9 to 15 Years Versus Participants Aged 16 to 26 Years Anti-HPV 16	3878.3 mMU/mL Interval 2908.5 to 5171.6	2294.8 mMU/mL Interval 2110.0 to 2495.7
Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18 Participants Aged 9 to 15 Years Versus Participants Aged 16 to 26 Years Anti-HPV 18	1114.5 mMU/mL Interval 871.6 to 1425.1	365.4 mMU/mL Interval 327.1 to 408.1

SECONDARY outcome

Timeframe: 12 months postdose 3 (18 months)

Population: All participants that received all 3 vaccinations within acceptable day ranges, were seronegative to the relevant HPV type at Day 1, did not have protocol violations that could interfere with evaluation of the immune response, and provided Month 18 data within an acceptable date range of 12 months postdose 3.

Antibodies to HPV Types 6, 11, 16, and 18 were measured using a competitive luminex immunoassay. Antibody titers were expressed as mMU/mL.

Outcome measures

Measure	V501 n=99 Participants 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6	Participants Aged 16 to 26 Years (PN122) 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6
Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18: Persistence at 18 Months Anti-HPV 6	222.0 mMU/mL Interval 181.8 to 271.3	—
Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18: Persistence at 18 Months Anti-HPV 11	259.9 mMU/mL Interval 210.7 to 320.7	—
Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18: Persistence at 18 Months Anti-HPV 16	1154.1 mMU/mL Interval 937.3 to 1421.0	—
Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18: Persistence at 18 Months Anti-HPV 18	212.1 mMU/mL Interval 165.6 to 271.7	—

SECONDARY outcome

Timeframe: 24 months postdose 3 (30 months)

Population: All participants that received all 3 vaccinations within acceptable day ranges, were seronegative to the relevant HPV type at Day 1, did not have protocol violations that could interfere with evaluation of the immune response, and provided Month 30 data within an acceptable date range of 24 months postdose 3.

Antibodies to HPV Types 6, 11, 16, and 18 were measured using a competitive luminex immunoassay. Antibody titers were expressed as mMU/mL.

Outcome measures

Measure	V501 n=99 Participants 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6	Participants Aged 16 to 26 Years (PN122) 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6
Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18: Persistence at 30 Months Anti-HPV 6	177.5 mMU/mL Interval 145.0 to 217.2	—
Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18: Persistence at 30 Months Anti-HPV 11	181.5 mMU/mL Interval 146.3 to 225.2	—
Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18: Persistence at 30 Months Anti-HPV 16	831.3 mMU/mL Interval 680.7 to 1015.1	—
Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18: Persistence at 30 Months Anti-HPV 18	144.2 mMU/mL Interval 112.2 to 185.2	—

SECONDARY outcome

Timeframe: 12 months postdose 3 (18 months)

Population: All participants that received all 3 vaccinations within acceptable day ranges, were seronegative to the relevant HPV type at Day 1, did not have protocol violations that could interfere with evaluation of the immune response, and provided Month 18 data within an acceptable date range of 12 months postdose 3.

Serum antibodies to HPV types were measured with a competitive luminex immunoassay. The serostatus cutoffs (mMU/mL) for HPV types were as follows: HPV Type 6: ≥20; HPV Type 11: ≥16; HPV Type 16: ≥20; HPV Type 18: ≥24

Outcome measures

Measure	V501 n=99 Participants 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6	Participants Aged 16 to 26 Years (PN122) 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6
Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18: Persistence at 18 Months Anti-HPV 6	97.9 Percentage of Participants Interval 92.7 to 99.7	—
Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18: Persistence at 18 Months Anti-HPV 11	100.0 Percentage of Participants Interval 96.3 to 100.0	—
Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18: Persistence at 18 Months Anti-HPV 16	99.0 Percentage of Participants Interval 94.4 to 100.0	—
Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18: Persistence at 18 Months Anti-HPV 18	94.8 Percentage of Participants Interval 88.4 to 98.3	—

SECONDARY outcome

Timeframe: 24 months postdose 3 (30 months)

Population: All participants that received all 3 vaccinations within acceptable day ranges, were seronegative to the relevant HPV type at Day 1, did not have protocol violations that could interfere with evaluation of the immune response, and provided Month 30 data within an acceptable date range of 24 months postdose 3.

Serum antibodies to HPV types were measured with a competitive luminex immunoassay. The serostatus cutoffs (mMU/mL) for HPV types were as follows: HPV Type 6: ≥20; HPV Type 11: ≥16; HPV Type 16: ≥20; HPV Type 18: ≥24.

Outcome measures

Measure	V501 n=99 Participants 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6	Participants Aged 16 to 26 Years (PN122) 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6
Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18: Persistence at 30 Months Anti-HPV 18	93.9 Percentage of Participants Interval 87.1 to 97.7	—
Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18: Persistence at 30 Months Anti-HPV 6	98.0 Percentage of Participants Interval 92.8 to 99.8	—
Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18: Persistence at 30 Months Anti-HPV 11	98.0 Percentage of Participants Interval 92.8 to 99.8	—
Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18: Persistence at 30 Months Anti-HPV 16	99.0 Percentage of Participants Interval 94.5 to 100.0	—

Adverse Events

V501

Serious events: 0 serious events

Other events: 67 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	V501 n=100 participants at risk 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6
General disorders Injection site erythema	31.0% 31/100 • Number of events 57 • Up to 30 months Population included all participants that received at least 1 vaccination
General disorders Injection site pain	57.0% 57/100 • Number of events 130 • Up to 30 months Population included all participants that received at least 1 vaccination
General disorders Injection site pruritus	6.0% 6/100 • Number of events 10 • Up to 30 months Population included all participants that received at least 1 vaccination
General disorders Injection site swelling	34.0% 34/100 • Number of events 63 • Up to 30 months Population included all participants that received at least 1 vaccination
General disorders Pyrexia	6.0% 6/100 • Number of events 8 • Up to 30 months Population included all participants that received at least 1 vaccination
Infections and infestations Nasopharyngitis	9.0% 9/100 • Number of events 11 • Up to 30 months Population included all participants that received at least 1 vaccination

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
• Publication restrictions are in place

Restriction type: OTHER