Trial Outcomes & Findings for Efficacy and Tolerability Study of V501 in Japanese Males (V501-122) (NCT NCT01862874)

Results Overview

Persistent infection was defined as 1) polymerase chain reaction (PCR) positive to HPV Type 6, 11, 16, or 18 in 2 consecutive anogenital or biopsy samples collected ≥4 months apart, or 2) Pathology Panel consensus diagnosis of condyloma acuminate, penile/perianal/perineal intraepithelial neoplasia (PIN), penile, perianal, or perineal cancer and PCR detection of HPV Type 6, 11, 16, or 18 in an adjacent section and PCR positive for the same HPV type at a separate adjacent visit. The combined incidence of HPV Type 6, 11, 16, or 18 persistent infection detected in samples from ≥2 consecutive visits ≥6 months apart was assessed.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1124 participants

Primary outcome timeframe

Up to Month 36

Results posted on

2019-04-02

Participant Flow

A total of 1129 participants were screened and 1124 were randomized.

Participant milestones

Participant milestones
Measure	V501 Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.	Placebo Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Overall Study STARTED	562	562
Overall Study Vaccination 1	561	562
Overall Study Vaccination 2	539	542
Overall Study Vaccination 3	530	532
Overall Study COMPLETED	483	485
Overall Study NOT COMPLETED	79	77

Reasons for withdrawal

Reasons for withdrawal
Measure	V501 Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.	Placebo Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Overall Study Randomized not treated	1	0
Overall Study Adverse Event	0	3
Overall Study Lost to Follow-up	26	29
Overall Study Physician Decision	5	3
Overall Study Withdrawn by parent/guardian	1	1
Overall Study Withdrawal by Subject	46	40
Overall Study Death	0	1

Baseline Characteristics

Efficacy and Tolerability Study of V501 in Japanese Males (V501-122)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	V501 n=562 Participants Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.	Placebo n=562 Participants Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.	Total n=1124 Participants Total of all reporting groups
Age, Continuous	22.6 Years STANDARD_DEVIATION 2.1 • n=5 Participants	22.6 Years STANDARD_DEVIATION 2.0 • n=7 Participants	22.6 Years STANDARD_DEVIATION 2.0 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	562 Participants n=5 Participants	562 Participants n=7 Participants	1124 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	562 Participants n=5 Participants	562 Participants n=7 Participants	1124 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Month 36

Population: Participants who were seronegative at Day 1 and PCR negative from Day 1 through Month 7 to the relevant HPV type, received all 3 vaccinations, did not deviate from the study protocol in ways that might interfere with vaccine efficacy, and had ≥1 follow-up visit after Month 7.

Persistent infection was defined as 1) polymerase chain reaction (PCR) positive to HPV Type 6, 11, 16, or 18 in 2 consecutive anogenital or biopsy samples collected ≥4 months apart, or 2) Pathology Panel consensus diagnosis of condyloma acuminate, penile/perianal/perineal intraepithelial neoplasia (PIN), penile, perianal, or perineal cancer and PCR detection of HPV Type 6, 11, 16, or 18 in an adjacent section and PCR positive for the same HPV type at a separate adjacent visit. The combined incidence of HPV Type 6, 11, 16, or 18 persistent infection detected in samples from ≥2 consecutive visits ≥6 months apart was assessed.

Outcome measures

Outcome measures
Measure	V501 n=1137 Person-years follow-up Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.	Placebo n=1123 Person-years follow-up Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Combined Incidence of HPV Type 6, 11, 16, or 18-related Persistent Infection	0.3 Cases per 100 person-years of follow-up	1.9 Cases per 100 person-years of follow-up

PRIMARY outcome

Timeframe: Up to 5 days after any vaccination

Population: Participants who received ≥1 study vaccination and had follow-up data available.

Body temperature (oral or oral equivalent) was recorded on the Vaccination Report Card (VRC). The percentage of participants with a maximum temperature ≥37.5°C was summarized.

Outcome measures

Outcome measures
Measure	V501 n=551 Participants Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.	Placebo n=557 Participants Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Percentage of Participants With Maximum Temperature ≥37.5°C Reported on the Vaccination Report Card	2.7 Percentage of participants	3.9 Percentage of participants

PRIMARY outcome

Timeframe: Up to 5 days after any vaccination

Population: Participants who received ≥1 study vaccination and had follow-up data available.

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 percentage of participants with an injection-site AE prompted on the VRC (erythema, pain, and swelling) was summarized.

Outcome measures

Outcome measures
Measure	V501 n=554 Participants Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.	Placebo n=559 Participants Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card Injection-site erythema	24.5 Percentage of participants	21.6 Percentage of participants
Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card Injection-site pain	54.9 Percentage of participants	48.5 Percentage of participants
Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card Injection-site swelling	21.3 Percentage of participants	14.5 Percentage of participants

PRIMARY outcome

Timeframe: Up to 15 days after any vaccination

Population: Participants who received ≥1 study vaccination and had follow-up data available.

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 percentage of participants with a systemic AE was summarized.

Outcome measures

Outcome measures
Measure	V501 n=554 Participants Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.	Placebo n=559 Participants Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Percentage of Participants With a Systemic Adverse Event	14.4 Percentage of participants	15.4 Percentage of participants

PRIMARY outcome

Timeframe: Up to 15 days after any vaccination

Population: Participants who received ≥1 study vaccination and had follow-up data available.

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. Vaccine-related AEs are those that were deemed possibly, probably, or definitely related to vaccine administration by the investigator. The percentage of participants with a vaccine-related systemic AE was summarized.

Outcome measures

Outcome measures
Measure	V501 n=554 Participants Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.	Placebo n=559 Participants Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Percentage of Participants With a Vaccine-related Systemic Adverse Event	3.4 Percentage of participants	5.0 Percentage of participants

SECONDARY outcome

Timeframe: Up to Month 36

Population: Participants who were seronegative at Day 1 and PCR negative from Day 1 through Month 7 to the relevant HPV type, received all 3 vaccinations, did not deviate from the study protocol in ways that might interfere with vaccine efficacy, and had ≥1 follow-up visit after Month 7.

Persistent infection was defined as 1) polymerase chain reaction (PCR) positive to HPV Type 6, 11, 16, or 18 in 2 consecutive anogenital or biopsy samples collected ≥4 months apart, or 2) Pathology Panel consensus diagnosis of condyloma acuminate, penile/perianal/perineal intraepithelial neoplasia (PIN), penile, perianal, or perineal cancer and PCR detection of HPV Type 6, 11, 16, or 18 in an adjacent section and PCR positive for the same HPV type at a separate adjacent visit. The incidence of persistent infection detected in samples from ≥2 consecutive visits ≥6 months apart was assessed. Disease was defined as HPV Type 6, 11, 16, or 18-related condyloma acuminate, PIN, penile, perianal, or perineal cancer. The combined incidence of HPV Type 6, 11, 16, or 18 persistent infection or disease was assessed.

Outcome measures

Outcome measures
Measure	V501 n=1148 Person-years follow-up Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.	Placebo n=1132 Person-years follow-up Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Combined Incidence of HPV Type 6, 11, 16, or 18-related Persistent Infection or Disease	0.3 Cases per 100 person-years at risk	1.9 Cases per 100 person-years at risk

Adverse Events

V501

Serious events: 0 serious events

Other events: 329 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 303 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	V501 n=554 participants at risk Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.	Placebo n=559 participants at risk Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Psychiatric disorders Completed suicide	0.00% 0/554 • Up to 36 months The at-risk population was participants who received ≥1 study vaccination and had follow-up data available	0.18% 1/559 • Number of events 1 • Up to 36 months The at-risk population was participants who received ≥1 study vaccination and had follow-up data available

Other adverse events

Other adverse events
Measure	V501 n=554 participants at risk Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.	Placebo n=559 participants at risk Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
General disorders Injection-site erythema	24.7% 137/554 • Number of events 217 • Up to 36 months The at-risk population was participants who received ≥1 study vaccination and had follow-up data available	21.8% 122/559 • Number of events 179 • Up to 36 months The at-risk population was participants who received ≥1 study vaccination and had follow-up data available
General disorders Injection-site pain	54.9% 304/554 • Number of events 563 • Up to 36 months The at-risk population was participants who received ≥1 study vaccination and had follow-up data available	48.5% 271/559 • Number of events 480 • Up to 36 months The at-risk population was participants who received ≥1 study vaccination and had follow-up data available
General disorders Injection-site swelling	21.3% 118/554 • Number of events 181 • Up to 36 months The at-risk population was participants who received ≥1 study vaccination and had follow-up data available	14.7% 82/559 • Number of events 121 • Up to 36 months The at-risk population was participants who received ≥1 study vaccination and had follow-up data available

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

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.
Publication restrictions are in place

Restriction type: OTHER