Trial Outcomes & Findings for Immunogenicity and Tolerability of Broad Spectrum Human Papillomavirus (HPV) Vaccine in Adult and Young Adult Women (V503-004) (NCT NCT03158220)

NCT ID: NCT03158220

Last Updated: 2019-11-21

Results Overview

Antibodies to the HPV types contained in V503 were measured using a competitive luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). Statistical comparisons between arms was performed for the HPV types considered oncogenic (HPV Types 16/18/31/33/45/52/58).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1212 participants
• Primary outcome timeframe: 4 weeks post vaccination 3 (Month 7)
• Results posted on: 2019-11-21

Participant Flow

Participant milestones

Measure	Women 16-26 Years of Age Young adult women 16- to 26-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.	Women 27-45 Years of Age Adult women 27- to 45-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.
Overall Study STARTED	570	642
Overall Study Vaccination 1	570	640
Overall Study Vaccination 2	563	635
Overall Study Vaccination 3	556	629
Overall Study COMPLETED	553	626
Overall Study NOT COMPLETED	17	16

Reasons for withdrawal

Measure	Women 16-26 Years of Age Young adult women 16- to 26-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.	Women 27-45 Years of Age Adult women 27- to 45-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.
Overall Study Screen Failure	0	1
Overall Study Withdrawal by Subject	8	9
Overall Study Status unknown	0	1
Overall Study Lost to Follow-up	8	5
Overall Study Physician Decision	1	0

Baseline Characteristics

Immunogenicity and Tolerability of Broad Spectrum Human Papillomavirus (HPV) Vaccine in Adult and Young Adult Women (V503-004)

Baseline characteristics by cohort

Measure	Women 16-26 Years of Age n=570 Participants Young adult women 16- to 26-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.	Women 27-45 Years of Age n=642 Participants Adult women 27- to 45-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.	Total n=1212 Participants Total of all reporting groups
Age, Continuous	21.6 years STANDARD_DEVIATION 2.8 • n=93 Participants	35.8 years STANDARD_DEVIATION 5.5 • n=4 Participants	29.1 years STANDARD_DEVIATION 8.3 • n=27 Participants
Sex: Female, Male Female	570 Participants n=93 Participants	642 Participants n=4 Participants	1212 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race/Ethnicity, Customized Hispanic	21 Participants n=93 Participants	7 Participants n=4 Participants	28 Participants n=27 Participants
Race/Ethnicity, Customized Not Hispanic	548 Participants n=93 Participants	634 Participants n=4 Participants	1182 Participants n=27 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race American Indian or Alaska Native	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants
Race Asian	17 Participants n=93 Participants	10 Participants n=4 Participants	27 Participants n=27 Participants
Race Black or African American	5 Participants n=93 Participants	3 Participants n=4 Participants	8 Participants n=27 Participants
Race Multiple	7 Participants n=93 Participants	1 Participants n=4 Participants	8 Participants n=27 Participants
Race White	539 Participants n=93 Participants	627 Participants n=4 Participants	1166 Participants n=27 Participants

PRIMARY outcome

Timeframe: 4 weeks post vaccination 3 (Month 7)

Population: Received all 3 vaccinations of the correct dose and within acceptable day ranges, had evaluable serology results at Day 1 and Month 7, must have been seronegative to the appropriate HPV type at Day 1 and had no protocol deviations that could interfere with the evaluation of participant's immune response to the 9vHPV vaccine.

Antibodies to the HPV types contained in V503 were measured using a competitive luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). Statistical comparisons between arms was performed for the HPV types considered oncogenic (HPV Types 16/18/31/33/45/52/58).

Outcome measures

Measure	Women 16-26 Years of Age n=485 Participants Young adult women 16- to 26-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.	Women 27-45 Years of Age n=533 Participants Adult women 27- to 45-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.
Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type Anti-HPV 31	596.1 mMU/mL Interval 551.1 to 644.9	395.7 mMU/mL Interval 367.0 to 426.6
Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type Anti-HPV 6	787.8 mMU/mL Interval 732.5 to 847.2	638.4 mMU/mL Interval 594.9 to 685.0
Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type Anti-HPV 11	598.7 mMU/mL Interval 558.7 to 641.6	453.5 mMU/mL Interval 424.1 to 485.0
Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type Anti-HPV 16	3075.8 mMU/mL Interval 2863.4 to 3303.9	2147.5 mMU/mL Interval 2001.1 to 2304.5
Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type Anti-HPV 18	744.5 mMU/mL Interval 685.0 to 809.1	532.1 mMU/mL Interval 491.8 to 575.7
Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type Anti-HPV 33	354.5 mMU/mL Interval 331.7 to 378.9	259.0 mMU/mL Interval 242.9 to 276.1
Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type Anti-HPV 45	214.9 mMU/mL Interval 197.7 to 233.7	145.6 mMU/mL Interval 134.4 to 157.7
Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type Anti-HPV 52	346.5 mMU/mL Interval 324.0 to 370.5	244.7 mMU/mL Interval 229.4 to 261.0
Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type Anti-HPV 58	428.0 mMU/mL Interval 399.4 to 458.6	296.4 mMU/mL Interval 277.1 to 317.0

SECONDARY outcome

Timeframe: Up to 1 month post vaccination 3 (up to 7 months)

Population: All participants that received at least 1 vaccination and had available data for endpoint.

An AE is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The percentage of participants with 1 or more AEs was assessed.

Outcome measures

Measure	Women 16-26 Years of Age n=570 Participants Young adult women 16- to 26-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.	Women 27-45 Years of Age n=640 Participants Adult women 27- to 45-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.
Percentage of Participants That Experienced at Least 1 Adverse Event (AE)	92.8 Percentage of Participants	92.5 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 1 month post vaccination 3 (up to 7 months)

Population: All participants that received at least 1 vaccination and had available data for endpoint.

An adverse event is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The percentage of participants who discontinued the study vaccine due to an adverse event regardless of study completion status was assessed.

Outcome measures

Measure	Women 16-26 Years of Age n=570 Participants Young adult women 16- to 26-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.	Women 27-45 Years of Age n=640 Participants Adult women 27- to 45-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.
Percentage of Participants Who Had Study Vaccine Discontinued Due to Adverse Event.	0.0 Percentage of Participants	0.2 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 5 days post any vaccination

Population: All participants that received at least 1 vaccination and had available data for endpoint.

Participants were asked to record any injection-site reactions prompted in the Vaccination Report Card, i.e., injection-site tenderness, swelling, or redness, occurring after each study vaccination (solicited injection-site reactions). The percentage of participants with 1 or more solicited injection-site AE was assessed.

Outcome measures

Measure	Women 16-26 Years of Age n=570 Participants Young adult women 16- to 26-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.	Women 27-45 Years of Age n=640 Participants Adult women 27- to 45-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.
Percentage of Participants With at Least 1 Solicited Injection-site Adverse Event	87.2 Percentage of Participants	84.7 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 15 days post any vaccination

Population: All participants that received at least 1 vaccination and had available data for endpoint.

An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can 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 is temporally associated with the study vaccine or protocol-specified procedure is also an AE. Systemic AEs are those not categorized as injection-site AEs. The percentage of participants that reported at least 1 systemic AE was assessed

Outcome measures

Measure	Women 16-26 Years of Age n=570 Participants Young adult women 16- to 26-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.	Women 27-45 Years of Age n=640 Participants Adult women 27- to 45-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.
Percentage of Participants That Reported at Least 1 Systemic Adverse Event	66.3 Percentage of Participants	64.4 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 5 days post any vaccination

Population: All participants that received at least 1 vaccination and had available data for endpoint.

Participants were asked to record oral body temperature in the Vaccination Report Card. The percentage of participants with elevated temperature (≥37.8°C or 100.0°F) was assessed.

Outcome measures

Measure	Women 16-26 Years of Age n=570 Participants Young adult women 16- to 26-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.	Women 27-45 Years of Age n=640 Participants Adult women 27- to 45-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.
Percentage of Participants With Elevated Temperature (Fever)	3.5 Percentage of Participants	2.5 Percentage of Participants

SECONDARY outcome

Timeframe: 4 weeks post vaccination 3 (Month 7)

Population: Received all 3 vaccinations of the correct dose and within acceptable day ranges, had evaluable serology results at Day 1 and Month 7, must have been seronegative to the appropriate HPV type at Day 1 and had no protocol deviations that could interfere with the evaluation of participant's immune response to the 9vHPV vaccine.

Antibodies to the HPV types contained in V503 were measured using a competitive luminex immunoassay. The percentage of participants who were seronegative on Day 1 and have anti-HPV titer greater or equal to the type-specific serostatus cutoff at 4 weeks postdose 3 was assessed.

Outcome measures

Measure	Women 16-26 Years of Age n=485 Participants Young adult women 16- to 26-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.	Women 27-45 Years of Age n=533 Participants Adult women 27- to 45-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.
Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types Anti HPV 16	100.0 Percentage of Participants Interval 99.2 to 100.0	100.0 Percentage of Participants Interval 99.2 to 100.0
Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types Anti HPV 18	100.0 Percentage of Participants Interval 99.1 to 100.0	99.6 Percentage of Participants Interval 98.5 to 99.9
Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types Anti HPV 58	100.0 Percentage of Participants Interval 99.2 to 100.0	99.8 Percentage of Participants Interval 98.8 to 100.0
Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types Anti HPV 6	99.8 Percentage of Participants Interval 98.7 to 100.0	100.0 Percentage of Participants Interval 99.2 to 100.0
Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types Anti HPV 11	100.0 Percentage of Participants Interval 99.1 to 100.0	99.8 Percentage of Participants Interval 98.8 to 100.0
Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types Anti HPV 31	100.0 Percentage of Participants Interval 99.2 to 100.0	99.8 Percentage of Participants Interval 98.9 to 100.0
Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types Anti HPV 33	100.0 Percentage of Participants Interval 99.2 to 100.0	99.8 Percentage of Participants Interval 98.9 to 100.0
Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types Anti HPV 45	99.6 Percentage of Participants Interval 98.5 to 99.9	99.2 Percentage of Participants Interval 98.0 to 99.8
Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types Anti HPV 52	100.0 Percentage of Participants Interval 99.2 to 100.0	100.0 Percentage of Participants Interval 99.3 to 100.0

Adverse Events

Women 16-26 Years of Age

Serious events: 6 serious events

Other events: 518 other events

Deaths: 0 deaths

Women 27-45 Years of Age

Serious events: 8 serious events

Other events: 574 other events

Deaths: 0 deaths

Serious adverse events

Measure	Women 16-26 Years of Age n=570 participants at risk Young adult women 16- to 26-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.	Women 27-45 Years of Age n=640 participants at risk Adult women 27- to 45-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.
Gastrointestinal disorders Abdominal pain	0.18% 1/570 • Number of events 1 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	0.00% 0/640 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
Infections and infestations Pneumonia	0.00% 0/570 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	0.16% 1/640 • Number of events 1 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
Infections and infestations Rectal abscess	0.18% 1/570 • Number of events 1 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	0.00% 0/640 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
Infections and infestations Tonsillitis	0.18% 1/570 • Number of events 1 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	0.16% 1/640 • Number of events 1 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
Injury, poisoning and procedural complications Cervical vertebral fracture	0.00% 0/570 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	0.16% 1/640 • Number of events 1 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
Injury, poisoning and procedural complications Head injury	0.18% 1/570 • Number of events 1 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	0.00% 0/640 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
Injury, poisoning and procedural complications Ligament injury	0.00% 0/570 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	0.16% 1/640 • Number of events 1 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/570 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	0.16% 1/640 • Number of events 1 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/570 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	0.16% 1/640 • Number of events 1 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
Nervous system disorders Basilar migraine	0.00% 0/570 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	0.16% 1/640 • Number of events 1 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
Pregnancy, puerperium and perinatal conditions Foetal death	0.00% 0/570 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	0.16% 1/640 • Number of events 1 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
Surgical and medical procedures Abortion induced	0.35% 2/570 • Number of events 2 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	0.16% 1/640 • Number of events 1 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.

Other adverse events

Measure	Women 16-26 Years of Age n=570 participants at risk Young adult women 16- to 26-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.	Women 27-45 Years of Age n=640 participants at risk Adult women 27- to 45-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6.
Gastrointestinal disorders Nausea	5.4% 31/570 • Number of events 35 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	4.2% 27/640 • Number of events 32 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
General disorders Fatigue	4.9% 28/570 • Number of events 36 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	5.2% 33/640 • Number of events 42 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
General disorders Injection site erythema	19.6% 112/570 • Number of events 166 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	17.3% 111/640 • Number of events 163 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
General disorders Injection site pain	86.3% 492/570 • Number of events 1246 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	83.1% 532/640 • Number of events 1244 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
General disorders Injection site swelling	24.0% 137/570 • Number of events 206 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	23.8% 152/640 • Number of events 224 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
General disorders Pyrexia	6.3% 36/570 • Number of events 40 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	4.4% 28/640 • Number of events 31 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
Infections and infestations Nasopharyngitis	9.3% 53/570 • Number of events 57 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	8.8% 56/640 • Number of events 69 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
Nervous system disorders Headache	32.5% 185/570 • Number of events 297 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	31.2% 200/640 • Number of events 320 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
Reproductive system and breast disorders Dysmenorrhoea	8.9% 51/570 • Number of events 65 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	3.4% 22/640 • Number of events 27 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.0% 40/570 • Number of events 44 • Up to 1 month post vaccination 3 (up to 7 months) Population included all participants that received at least 1 vaccination.	7.2% 46/640 • Number of events 53 • Up to 1 month post vaccination 3 (up to 7 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