Trial Outcomes & Findings for Immunogenicity and Tolerability of V503 Versus GARDASIL (V503-009) (NCT NCT01304498)

NCT ID: NCT01304498

Last Updated: 2018-12-14

Results Overview

Serum antibodies to HPV types 16 and 18 were measured with a Competitive Luminex Immunoassay.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 600 participants
• Primary outcome timeframe: 4 weeks postdose 3 (Month 7)
• Results posted on: 2018-12-14

Participant Flow

A total of 603 participants were screened and 600 were randomized

Participant milestones

Measure	V503 9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6	GARDASIL Quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6
Overall Study STARTED	300	300
Overall Study Received ≥1 Dose	300	300
Overall Study COMPLETED	294	295
Overall Study NOT COMPLETED	6	5

Reasons for withdrawal

Measure	V503 9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6	GARDASIL Quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6
Overall Study Adverse Event	1	1
Overall Study Withdrawal by Subject	2	3
Overall Study Protocol Violation	1	0
Overall Study Lost to Follow-up	2	1

Baseline Characteristics

Immunogenicity and Tolerability of V503 Versus GARDASIL (V503-009)

Baseline characteristics by cohort

Measure	V503 n=300 Participants 9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6	GARDASIL n=300 Participants Quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6	Total n=600 Participants Total of all reporting groups
Age, Continuous	12.6 Years STANDARD_DEVIATION 1.9 • n=5 Participants	12.6 Years STANDARD_DEVIATION 1.9 • n=7 Participants	12.6 Years STANDARD_DEVIATION 1.9 • n=5 Participants
Age, Customized 9 to 12 years old	150 Participants n=5 Participants	150 Participants n=7 Participants	300 Participants n=5 Participants
Age, Customized 13 to 15 years old	150 Participants n=5 Participants	150 Participants n=7 Participants	300 Participants n=5 Participants
Sex: Female, Male Female	300 Participants n=5 Participants	300 Participants n=7 Participants	600 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 weeks postdose 3 (Month 7)

Population: All randomized participants. The n values are participants who received all 3 vaccinations within acceptable day ranges, had Month 7 serology to the HPV type within acceptable day ranges, were seronegative to the HPV type at Day 1, and had no protocol violations that interfered with evaluation of immune response.

Serum antibodies to HPV types 16 and 18 were measured with a Competitive Luminex Immunoassay.

Outcome measures

Measure	V503 n=300 Participants 9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6	GARDASIL n=300 Participants Quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6
Geometric Mean Titers (GMTs) to HPV Types 16 and 18 HPV Type 16 (n=276, 270)	6739.5 milli Merck Units/mL Interval 6134.5 to 7404.1	6887.4 milli Merck Units/mL Interval 6220.8 to 7625.5
Geometric Mean Titers (GMTs) to HPV Types 16 and 18 HPV Type 18 (n=276, 269)	1956.6 milli Merck Units/mL Interval 1737.3 to 2203.7	1795.6 milli Merck Units/mL Interval 1567.2 to 2057.3

SECONDARY outcome

Timeframe: 4 weeks postdose 3 (Month 7)

Population: All randomized participants. The n values are participants who received all 3 vaccinations within acceptable day ranges, had Month 7 serology to the HPV type within acceptable day ranges, were seronegative to the HPV type at Day 1, and had no protocol violations that interfered with evaluation of immune response.

Serum antibodies to HPV types 6 and 11 were measured with a Competitive Luminex Immunoassay.

Outcome measures

Measure	V503 n=300 Participants 9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6	GARDASIL n=300 Participants Quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6
GMTs to HPV Types 6 and 11 HPV Type 6 (n=273, 261)	1679.4 milli Merck Units/mL Interval 1518.9 to 1856.9	1565.9 milli Merck Units/mL Interval 1412.2 to 1736.3
GMTs to HPV Types 6 and 11 HPV Type 11 (n=273, 261)	1315.6 milli Merck Units/mL Interval 1183.8 to 1462.0	1417.3 milli Merck Units/mL Interval 1274.2 to 1576.5

SECONDARY outcome

Timeframe: 4 weeks postdose 3 (Month 7)

Population: All randomized participants. The n values are participants who received all 3 vaccinations within acceptable day ranges, had Month 7 serology to the HPV type within acceptable day ranges, were seronegative to the HPV type at Day 1, and had no protocol violations that interfered with evaluation of immune response.

Serum antibodies to HPV types were measured with a Competitive Luminex Immunoassay. The serostatus cutoffs (milli Merck Units/mL) for HPV types were as follows: HPV Type 6: ≥30; HPV Type 11: ≥16; HPV Type 16: ≥20; HPV Type 18: ≥24. The percentage of participants who were seropositive according to these cutoffs was assessed.

Outcome measures

Measure	V503 n=300 Participants 9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6	GARDASIL n=300 Participants Quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6
Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18 HPV Type 6 (n=273, 261)	100 Percentage of participants Interval 98.7 to 100.0	100 Percentage of participants Interval 98.6 to 100.0
Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18 HPV Type 11 (n=273, 261)	100 Percentage of participants Interval 98.7 to 100.0	100 Percentage of participants Interval 98.6 to 100.0
Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18 HPV Type 16 (n=276, 270)	100 Percentage of participants Interval 98.7 to 100.0	100 Percentage of participants Interval 98.6 to 100.0
Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18 HPV Type 18 (n=276, 269)	100 Percentage of participants Interval 98.7 to 100.0	100 Percentage of participants Interval 98.6 to 100.0

SECONDARY outcome

Timeframe: Up to Month 7

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

An adverse event is defined as any unfavourable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine, is also an adverse event. The percentage of participants with one or more adverse events was assessed.

Outcome measures

Measure	V503 n=299 Participants 9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6	GARDASIL n=300 Participants Quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6
Percentage of Participants With One or More Adverse Events	96.0 Percentage of participants Interval 87.9 to 94.5	93.7 Percentage of participants Interval 84.1 to 91.7

SECONDARY outcome

Timeframe: Up to 5 days after any vaccination

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

The percentage of participants with one or more injection-site adverse reactions (solicited or unsolicited) was assessed.

Outcome measures

Measure	V503 n=299 Participants 9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6	GARDASIL n=300 Participants Quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6
Percentage of Participants With One or More Injection-site Adverse Reactions	91.6 Percentage of participants Interval 87.9 to 94.5	88.3 Percentage of participants Interval 84.1 to 91.7

SECONDARY outcome

Timeframe: Up to 15 days after any vaccination

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

The percentage of participants with one or more systemic adverse events was assessed.

Outcome measures

Measure	V503 n=299 Participants 9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6	GARDASIL n=300 Participants Quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6
Percentage of Participants With One or More Systemic Adverse Events	47.5 Percentage of participants Interval 41.7 to 53.3	52.0 Percentage of participants Interval 46.2 to 57.8

SECONDARY outcome

Timeframe: Up to 15 days after any vaccination

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

The percentage of participants with maximum oral temperature ≥37.8°C was assessed.

Outcome measures

Measure	V503 n=299 Participants 9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6	GARDASIL n=300 Participants Quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6
Percentage of Participants With Maximum Oral Temperature ≥37.8°C	6.7 Percentage of participants Interval 4.1 to 10.1	3.3 Percentage of participants Interval 1.6 to 6.0

SECONDARY outcome

Timeframe: Up to Month 7

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

A serious adverse event is an adverse event that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs a hospitalization, is a congenital anomaly or birth defect, is a cancer, or may jeopardize the participant and may require medical or surgical intervention. The percentage of participants with one or more serious adverse events was assessed.

Outcome measures

Measure	V503 n=299 Participants 9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6	GARDASIL n=300 Participants Quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6
Percentage of Participants With One or More Serious Adverse Events	0.3 Percentage of participants	0.7 Percentage of participants

Adverse Events

V503

Serious events: 1 serious events

Other events: 280 other events

Deaths: 0 deaths

GARDASIL

Serious events: 2 serious events

Other events: 274 other events

Deaths: 0 deaths

Serious adverse events

Measure	V503 n=299 participants at risk 9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6	GARDASIL n=300 participants at risk Quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6
Blood and lymphatic system disorders Anaemia	0.33% 1/299 • Number of events 1 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7	0.00% 0/300 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7
Nervous system disorders Complex partial seizures	0.00% 0/299 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7	0.33% 1/300 • Number of events 1 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7
Respiratory, thoracic and mediastinal disorders Pulmonary vasculitis	0.33% 1/299 • Number of events 1 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7	0.00% 0/300 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7
Skin and subcutaneous tissue disorders Henoch-Schonlein purpura	0.00% 0/299 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7	0.33% 1/300 • Number of events 1 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7

Other adverse events

Measure	V503 n=299 participants at risk 9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6	GARDASIL n=300 participants at risk Quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine, 0.5-mL intramuscular injection in 3 dose regimen at Day 1, Month 2, and Month 6
Gastrointestinal disorders Nausea	5.4% 16/299 • Number of events 17 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7	5.3% 16/300 • Number of events 17 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7
General disorders Injection-site erythema	34.1% 102/299 • Number of events 132 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7	29.3% 88/300 • Number of events 129 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7
General disorders Injection-site pain	90.0% 269/299 • Number of events 675 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7	88.7% 266/300 • Number of events 626 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7
General disorders Injection-site swelling	48.2% 144/299 • Number of events 226 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7	36.3% 109/300 • Number of events 160 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7
General disorders Pyrexia	7.4% 22/299 • Number of events 23 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7	5.7% 17/300 • Number of events 17 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7
Infections and infestations Nasopharyngitis	1.7% 5/299 • Number of events 7 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7	5.3% 16/300 • Number of events 18 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7
Nervous system disorders Headache	19.1% 57/299 • Number of events 84 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7	19.0% 57/300 • Number of events 93 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.4% 16/299 • Number of events 17 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7	5.7% 17/300 • Number of events 18 • All adverse events: up to 15 days after each vaccination; serious adverse events: up to Month 7

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 study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission.
• Publication restrictions are in place

Restriction type: OTHER