Trial Outcomes & Findings for GARDASIL™ Study in Healthy Females Between 9 and 26 Years of Age in Sub-Saharan Africa (V501-046) (NCT NCT01245764)

Results Overview

Seroconversion was defined as achieving an anti-HPV Type 6 competitive Luminex Immunoassay (cLIA) level of \>=20 milli Merck U/mL. The dilution-corrected limit of detection for the Type 6 cLIA was 4.2 milli Merck U/mL.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

250 participants

Primary outcome timeframe

Month 7 (1 month postdose 3 in study Phase A)

Results posted on

2018-11-14

Participant Flow

Participant milestones

Participant milestones
Measure	GARDASIL 9 to 12 Years Old GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. Immunogenicity was assessed at Month 7 of study Phase A and safety evaluation continued to Month 12 (total study duration up to 12 months). Participants did not continue to study Phase B.	GARDASIL 13 to 15 Years Old GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. Immunogenicity was assessed at Month 7 of study Phase A and safety evaluation continued to Month 12 (total study duration up to 12 months). Participants did not continue to study Phase B.	GARDASIL 16 to 26 Years Old GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. Immunogenicity was assessed at Month 7 of study Phase A and safety evaluation continued to Month 12 (total study duration up to 12 months). Participants did not continue to study Phase B.	Placebo 9 to 12 Years Old Placebo to GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. Immunogenicity was assessed at Month 7 of study Phase A. After database lock and unblinding for study Phase A, participants had the option to receive GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase B. Safety evaluation continued to Month 7 of study Phase B (total study duration up to 19 months)
Study Phase A STARTED	80	30	120	20
Study Phase A Completed Vaccinations in Study Phase A	77	28	117	19
Study Phase A COMPLETED	71	25	110	17
Study Phase A NOT COMPLETED	9	5	10	3
Study Phase B STARTED	0	0	0	17
Study Phase B Completed Vaccinations in Study Phase B	0	0	0	17
Study Phase B COMPLETED	0	0	0	17
Study Phase B NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	GARDASIL 9 to 12 Years Old GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. Immunogenicity was assessed at Month 7 of study Phase A and safety evaluation continued to Month 12 (total study duration up to 12 months). Participants did not continue to study Phase B.	GARDASIL 13 to 15 Years Old GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. Immunogenicity was assessed at Month 7 of study Phase A and safety evaluation continued to Month 12 (total study duration up to 12 months). Participants did not continue to study Phase B.	GARDASIL 16 to 26 Years Old GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. Immunogenicity was assessed at Month 7 of study Phase A and safety evaluation continued to Month 12 (total study duration up to 12 months). Participants did not continue to study Phase B.	Placebo 9 to 12 Years Old Placebo to GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. Immunogenicity was assessed at Month 7 of study Phase A. After database lock and unblinding for study Phase A, participants had the option to receive GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase B. Safety evaluation continued to Month 7 of study Phase B (total study duration up to 19 months)
Study Phase A Other	3	2	3	1
Study Phase A Protocol Violation	6	3	2	2
Study Phase A Lost to Follow-up	0	0	5	0

Baseline Characteristics

GARDASIL™ Study in Healthy Females Between 9 and 26 Years of Age in Sub-Saharan Africa (V501-046)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GARDASIL 9 to 12 Years Old n=80 Participants GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. Immunogenicity was assessed at Month 7 of study Phase A and safety evaluation continued to Month 12 (total study duration up to 12 months). Participants did not continue to study Phase B.	GARDASIL 13 to 15 Years Old n=30 Participants GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. Immunogenicity was assessed at Month 7 of study Phase A and safety evaluation continued to Month 12 (total study duration up to 12 months). Participants did not continue to study Phase B.	GARDASIL 16 to 26 Years Old n=120 Participants GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. Immunogenicity was assessed at Month 7 of study Phase A and safety evaluation continued to Month 12 (total study duration up to 12 months). Participants did not continue to study Phase B.	Placebo 9 to 12 Years Old n=20 Participants Placebo to GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. Immunogenicity was assessed at Month 7 of study Phase A. After database lock and unblinding for study Phase A, participants had the option to receive GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase B. Safety evaluation continued to Month 7 of study Phase B (total study duration up to 19 months)	Total n=250 Participants Total of all reporting groups
Age, Customized <9 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Customized 9 to 12 years	80 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	20 Participants n=4 Participants	100 Participants n=21 Participants
Age, Customized 13 to 15 years	0 Participants n=5 Participants	30 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	30 Participants n=21 Participants
Age, Customized 16 to 26 years	0 Participants n=5 Participants	0 Participants n=7 Participants	120 Participants n=5 Participants	0 Participants n=4 Participants	120 Participants n=21 Participants
Age, Customized >26 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Female	80 Participants n=5 Participants	30 Participants n=7 Participants	120 Participants n=5 Participants	20 Participants n=4 Participants	250 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race/Ethnicity, Customized Black	80 Participants n=5 Participants	30 Participants n=7 Participants	119 Participants n=5 Participants	20 Participants n=4 Participants	249 Participants n=21 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Island	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants

PRIMARY outcome

Timeframe: Month 7 (1 month postdose 3 in study Phase A)

Population: Participants analyzed included those who received all 3 vaccinations in study Phase A and provided a sample for Month 7 serology testing. This analysis pooled results for participants receiving GARDASIL and compared these with results for participants receiving placebo.

Seroconversion was defined as achieving an anti-HPV Type 6 competitive Luminex Immunoassay (cLIA) level of \>=20 milli Merck U/mL. The dilution-corrected limit of detection for the Type 6 cLIA was 4.2 milli Merck U/mL.

Outcome measures

Outcome measures
Measure	GARDASIL 9 to 26 Years Old n=147 Participants GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	Placebo 9 to 12 Years Old n=13 Participants Placebo to GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	GARDASIL 16 to 26 Years Old GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A	Placebo 9 to 12 Years Old Placebo to match GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A
Number of Participants Who Seroconvert to Human Papillomavirus (HPV) Type 6	147 Participants	1 Participants	—	—

PRIMARY outcome

Timeframe: Month 7 (1 month postdose 3 in study Phase A)

Population: Participants analyzed included those who received all 3 vaccinations in study Phase A and provided a sample for Month 7 serology testing. This analysis pooled results for participants receiving GARDASIL and compared these with results for participants receiving placebo.

Seroconversion was defined as achieving an anti-HPV Type 11 cLIA level of \>=16 milli Merck U/mL. The dilution-corrected limit of detection for the Type 11 cLIA was 3.9 milli Merck U/mL.

Outcome measures

Outcome measures
Measure	GARDASIL 9 to 26 Years Old n=147 Participants GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	Placebo 9 to 12 Years Old n=13 Participants Placebo to GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	GARDASIL 16 to 26 Years Old GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A	Placebo 9 to 12 Years Old Placebo to match GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A
Number of Participants Who Seroconvert to HPV Type 11	147 Participants	1 Participants	—	—

PRIMARY outcome

Timeframe: Month 7 (1 month postdose 3 in study Phase A)

Population: Participants analyzed included those who received all 3 vaccinations in study Phase A and provided a sample for Month 7 serology testing. This analysis pooled results for participants receiving GARDASIL and compared these with results for participants receiving placebo.

Seroconversion was defined as achieving an anti-HPV Type 16 cLIA level of \>=20 milli Merck U/mL. The dilution-corrected limit of detection for the Type 16 cLIA was 9.7 milli Merck U/mL.

Outcome measures

Outcome measures
Measure	GARDASIL 9 to 26 Years Old n=160 Participants GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	Placebo 9 to 12 Years Old n=14 Participants Placebo to GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	GARDASIL 16 to 26 Years Old GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A	Placebo 9 to 12 Years Old Placebo to match GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A
Number of Participants Who Seroconvert to HPV Type 16	160 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: Month 7 (1 month postdose 3 in study Phase A)

Population: Participants analyzed included those who received all 3 vaccinations in study Phase A and provided a sample for Month 7 serology testing. This analysis pooled results for participants receiving GARDASIL and compared these with results for participants receiving placebo.

Seroconversion was defined as achieving an anti-HPV Type 18 cLIA level of \>=24 milli Merck U/mL. The dilution-corrected limit of detection for the Type 18 cLIA was 5.8 milli Merck U/mL.

Outcome measures

Outcome measures
Measure	GARDASIL 9 to 26 Years Old n=156 Participants GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	Placebo 9 to 12 Years Old n=14 Participants Placebo to GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	GARDASIL 16 to 26 Years Old GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A	Placebo 9 to 12 Years Old Placebo to match GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A
Number of Participants Who Seroconvert to HPV Type 18	156 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: Up to Day 5 after any vaccination in study Phase A

Population: The analysis included all participants receiving at least 1 vaccination in study Phase A and who had postvaccination follow-up

Participants were prompted to report injection-site experiences of pain, erythema, or swelling and were also asked to report any other injection-site adverse experiences

Outcome measures

Outcome measures
Measure	GARDASIL 9 to 26 Years Old n=79 Participants GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	Placebo 9 to 12 Years Old n=29 Participants Placebo to GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	GARDASIL 16 to 26 Years Old n=119 Participants GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A	Placebo 9 to 12 Years Old n=19 Participants Placebo to match GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A
Number of Participants With Injection-site Adverse Experiences	54 Participants	21 Participants	88 Participants	9 Participants

PRIMARY outcome

Timeframe: Up to Day 5 after any vaccination in study Phase A

Population: The analysis included all participants receiving at least 1 vaccination in study Phase A and who had temperature data

Outcome measures

Outcome measures
Measure	GARDASIL 9 to 26 Years Old n=79 Participants GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	Placebo 9 to 12 Years Old n=29 Participants Placebo to GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	GARDASIL 16 to 26 Years Old n=119 Participants GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A	Placebo 9 to 12 Years Old n=19 Participants Placebo to match GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A
Number of Participants With Elevated Temperature (Oral Temperature >=100 °F)	9 Participants	6 Participants	7 Participants	5 Participants

PRIMARY outcome

Timeframe: From the time of informed consent is signed through the last study visit (up to 19 months)

Population: The analysis included all participants receiving at least 1 vaccination in study Phase A or B and who had postvaccination follow-up

A serious adverse experience is any adverse experience that results in death, is life threatening, results in persistent or significant disability/incapacity, results in or prolongs existing inpatient hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose, or is another important medical event that may jeopardize the participant and may require medical or surgical intervention

Outcome measures

Outcome measures
Measure	GARDASIL 9 to 26 Years Old n=79 Participants GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	Placebo 9 to 12 Years Old n=29 Participants Placebo to GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	GARDASIL 16 to 26 Years Old n=119 Participants GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A	Placebo 9 to 12 Years Old n=19 Participants Placebo to match GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A
Number of Participants With Serious Adverse Experiences	0 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Month 7 (1 month postdose 3 in study Phase A)

Population: Participants analyzed included those who received all 3 vaccinations in study Phase A and provided a sample for Month 7 serology testing. This analysis pooled results for participants receiving GARDASIL and compared these with results for participants receiving placebo.

Anti-HPV Type 6 antibodies were measured by cLIA. The seropositive cut-off threshold for this assay is defined as 20 milli Merck U/mL.

Outcome measures

Outcome measures
Measure	GARDASIL 9 to 26 Years Old n=147 Participants GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	Placebo 9 to 12 Years Old n=13 Participants Placebo to GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	GARDASIL 16 to 26 Years Old GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A	Placebo 9 to 12 Years Old Placebo to match GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A
Geometric Mean Titer (GMT) of Anti-HPV Type 6 Antibody	602 milli Merck U/mL Interval 526.0 to 689.0	NA milli Merck U/mL GMT value was \<10 milli Merck U/mL	—	—

SECONDARY outcome

Timeframe: Month 7 (1 month postdose 3 in study Phase A)

Population: Participants analyzed included those who received all 3 vaccinations in study Phase A and provided a sample for Month 7 serology testing. This analysis pooled results for participants receiving GARDASIL and compared these with results for participants receiving placebo.

Anti-HPV Type 11 antibodies were measured by cLIA. The seropositive cut-off threshold for this assay is defined as 16 milli Merck U/mL.

Outcome measures

Outcome measures
Measure	GARDASIL 9 to 26 Years Old n=147 Participants GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	Placebo 9 to 12 Years Old n=13 Participants Placebo to GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	GARDASIL 16 to 26 Years Old GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A	Placebo 9 to 12 Years Old Placebo to match GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A
GMT of Anti-HPV Type 11 Antibody	626 milli Merck U/mL Interval 545.0 to 718.0	NA milli Merck U/mL GMT value was \<7 milli Merck U/mL	—	—

SECONDARY outcome

Timeframe: Month 7 (1 month postdose 3 in study Phase A)

Population: Participants analyzed included those who received all 3 vaccinations in study Phase A and provided a sample for Month 7 serology testing. This analysis pooled results for participants receiving GARDASIL and compared these with results for participants receiving placebo.

Anti-HPV Type 16 antibodies were measured by cLIA. The seropositive cut-off threshold for this assay is defined as 20 milli Merck U/mL.

Outcome measures

Outcome measures
Measure	GARDASIL 9 to 26 Years Old n=160 Participants GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	Placebo 9 to 12 Years Old n=14 Participants Placebo to GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	GARDASIL 16 to 26 Years Old GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A	Placebo 9 to 12 Years Old Placebo to match GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A
GMT of Anti-HPV Type 16 Antibody	3786 milli Merck U/mL Interval 3360.0 to 4265.0	NA milli Merck U/mL GMT value was \<9 milli Merck U/mL	—	—

SECONDARY outcome

Timeframe: Month 7 (1 month postdose 3 in study Phase A)

Population: Participants analyzed included those who received all 3 vaccinations in study Phase A and provided a sample for Month 7 serology testing. This analysis pooled results for participants receiving GARDASIL and compared these with results for participants receiving placebo.

Anti-HPV Type 18 antibodies were measured by cLIA. The seropositive cut-off threshold for this assay is defined as 24 milli Merck U/mL.

Outcome measures

Outcome measures
Measure	GARDASIL 9 to 26 Years Old n=156 Participants GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	Placebo 9 to 12 Years Old n=14 Participants Placebo to GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A.	GARDASIL 16 to 26 Years Old GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A	Placebo 9 to 12 Years Old Placebo to match GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A
GMT of Anti-HPV Type 18 Antibody	811 milli Merck U/mL Interval 708.0 to 928.0	NA milli Merck U/mL GMT value was \<15 milli Merck U/mL	—	—

Adverse Events

GARDASIL 9 to 12 Years Old

Serious events: 0 serious events

Other events: 61 other events

Deaths: 0 deaths

GARDASIL 13 to 15 Years Old

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

GARDASIL 16 to 26 Years Old

Serious events: 1 serious events

Other events: 103 other events

Deaths: 0 deaths

Placebo 9 to 12 Years Old

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GARDASIL 9 to 12 Years Old n=79 participants at risk GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. Participants did not continue to study Phase B.	GARDASIL 13 to 15 Years Old n=29 participants at risk GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. Participants did not continue to study Phase B.	GARDASIL 16 to 26 Years Old n=119 participants at risk GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. Participants did not continue to study Phase B.	Placebo 9 to 12 Years Old n=19 participants at risk Placebo to GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. After database lock and unblinding for study Phase A, participants had the option to receive GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase B.
Pregnancy, puerperium and perinatal conditions Foetal distress syndrome	0.00% 0/79 • Serious adverse events were assessed up to 19 months from study start. Other adverse events were assessed up to 15 days after each vaccination in study Phase A. The analysis included all participants receiving at least one vaccination and had at least one postvaccination follow-up visit.	0.00% 0/29 • Serious adverse events were assessed up to 19 months from study start. Other adverse events were assessed up to 15 days after each vaccination in study Phase A. The analysis included all participants receiving at least one vaccination and had at least one postvaccination follow-up visit.	0.84% 1/119 • Number of events 1 • Serious adverse events were assessed up to 19 months from study start. Other adverse events were assessed up to 15 days after each vaccination in study Phase A. The analysis included all participants receiving at least one vaccination and had at least one postvaccination follow-up visit.	0.00% 0/19 • Serious adverse events were assessed up to 19 months from study start. Other adverse events were assessed up to 15 days after each vaccination in study Phase A. The analysis included all participants receiving at least one vaccination and had at least one postvaccination follow-up visit.

Other adverse events

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 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