Trial Outcomes & Findings for Evaluation of the Safety and Tolerability of a Higher Potency Dose of an Investigational Vaccine Among Adults 50 Years of Age and Older (V211-009) (NCT NCT00092417)

NCT ID: NCT00092417

Last Updated: 2015-10-07

Results Overview

The incidence of vaccine-related SAEs occurring Day 1 through Day 42 postvaccination. Whether a serious clinical adverse experience occurring Day 1 through Day 42 postvaccination was vaccine-related was determined by the investigator who was a qualified physician . The difference in the risk of developing a vaccine-related SAE between the two groups was compared at the 2-sided 0.05 level.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 695 participants
• Primary outcome timeframe: Day 1-42 post vaccination
• Results posted on: 2015-10-07

Participant Flow

Participants were recruited at 18 sites in the United States, Canada, and Europe Prime Therapy Period: 30-Oct-2003 to 07-Jun-2004 Cutoff date for in-house data: 24-Aug-2004

Participant milestones

Measure	Zoster Vaccine Higher Potency Higher potency Zoster vaccine (approximately 207,000 plaque-forming units \[PFU\]), 1 subcutaneous 0.65 mL injection	Zoster Vaccine Lower Potency Lower potency Zoster vaccine (approximately 58,000 PFU), 1 subcutaneous 0.65 mL injection
Overall Study STARTED	464	234
Overall Study Vaccinated	461	234
Overall Study COMPLETED	459	233
Overall Study NOT COMPLETED	5	1

Reasons for withdrawal

Measure	Zoster Vaccine Higher Potency Higher potency Zoster vaccine (approximately 207,000 plaque-forming units \[PFU\]), 1 subcutaneous 0.65 mL injection	Zoster Vaccine Lower Potency Lower potency Zoster vaccine (approximately 58,000 PFU), 1 subcutaneous 0.65 mL injection
Overall Study Lost to Follow-up	2	0
Overall Study Withdrawal by Subject	2	1
Overall Study Other	1	0

Baseline Characteristics

Evaluation of the Safety and Tolerability of a Higher Potency Dose of an Investigational Vaccine Among Adults 50 Years of Age and Older (V211-009)

Baseline characteristics by cohort

Measure	Zoster Vaccine Higher Potency n=461 Participants Higher potency Zoster vaccine (approximately 207,000 plaque-forming units \[PFU\]), 1 subcutaneous 0.65 mL injection	Zoster Vaccine Lower Potency n=234 Participants Lower potency Zoster vaccine (approximately 58,000 PFU), 1 subcutaneous 0.65 mL injection	Total n=695 Participants Total of all reporting groups
Age, Continuous	65.2 years STANDARD_DEVIATION 9.16 • n=5 Participants	65.6 years STANDARD_DEVIATION 9.69 • n=7 Participants	65.4 years STANDARD_DEVIATION 9.34 • n=5 Participants
Sex: Female, Male Female	282 Participants n=5 Participants	134 Participants n=7 Participants	416 Participants n=5 Participants
Sex: Female, Male Male	179 Participants n=5 Participants	100 Participants n=7 Participants	279 Participants n=5 Participants
Race/Ethnicity, Customized Asian	10 participants n=5 Participants	6 participants n=7 Participants	16 participants n=5 Participants
Race/Ethnicity, Customized Black	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants
Race/Ethnicity, Customized Hispanic American	10 participants n=5 Participants	8 participants n=7 Participants	18 participants n=5 Participants
Race/Ethnicity, Customized Multi-Racial	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Native American	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized White	432 participants n=5 Participants	214 participants n=7 Participants	646 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1-42 post vaccination

Population: The population for the primary safety analysis consisted of all vaccinated participants who had safety follow-up data.

The incidence of vaccine-related SAEs occurring Day 1 through Day 42 postvaccination. Whether a serious clinical adverse experience occurring Day 1 through Day 42 postvaccination was vaccine-related was determined by the investigator who was a qualified physician . The difference in the risk of developing a vaccine-related SAE between the two groups was compared at the 2-sided 0.05 level.

Outcome measures

Measure	Zoster Vaccine Higher Potency n=459 Participants Higher potency Zoster vaccine (approximately 207,000 plaque-forming units \[PFU\]), 1 subcutaneous 0.65 mL injection	Zoster Vaccine Lower Potency n=234 Participants Lower potency Zoster vaccine (approximately 58,000 PFU), 1 subcutaneous 0.65 mL injection
Number of Participants With Vaccine-related Serious Clinical Adverse Experiences (SAEs) With vaccine-related SAEs	0 Participants	0 Participants
Number of Participants With Vaccine-related Serious Clinical Adverse Experiences (SAEs) Without vaccine-related SAEs	459 Participants	234 Participants

PRIMARY outcome

Timeframe: Day 1-5 postvaccination

Population: The population for the primary safety analysis consisted of all vaccinated participants who had safety follow-up data.

Outcome measures

Measure	Zoster Vaccine Higher Potency n=459 Participants Higher potency Zoster vaccine (approximately 207,000 plaque-forming units \[PFU\]), 1 subcutaneous 0.65 mL injection	Zoster Vaccine Lower Potency n=234 Participants Lower potency Zoster vaccine (approximately 58,000 PFU), 1 subcutaneous 0.65 mL injection
Number of Participants With Moderate or Severe Injection-site Pain/Tenderness/Soreness or Swelling (> 2 Inches at Largest Diameter) With moderate or severe injection-site reaction	79 Participants	21 Participants
Number of Participants With Moderate or Severe Injection-site Pain/Tenderness/Soreness or Swelling (> 2 Inches at Largest Diameter) Without moderate or severe injection-site reaction	380 Participants	213 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1-42 postvaccination

Population: The population for the safety analyses consisted of all vaccinated participants who had safety follow-up data.

Noninjection-site rash Day 1 through Day 42 postvaccination was reported by the participant to the investigator and confirmed to be varicelliform rash by the study physician and polymerase chain reaction (PCR).

Outcome measures

Measure	Zoster Vaccine Higher Potency n=459 Participants Higher potency Zoster vaccine (approximately 207,000 plaque-forming units \[PFU\]), 1 subcutaneous 0.65 mL injection	Zoster Vaccine Lower Potency n=234 Participants Lower potency Zoster vaccine (approximately 58,000 PFU), 1 subcutaneous 0.65 mL injection
Number of Participants With Varicella or Varicella-like Noninjection-site Rashes, Nondermatomal in Distribution With >100 Lesions With varicella or rash, varicelliform	0 Participants	0 Participants
Number of Participants With Varicella or Varicella-like Noninjection-site Rashes, Nondermatomal in Distribution With >100 Lesions Without varicella or rash, varicelliform	459 Participants	234 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1-42 postvaccination

Population: The population for the safety analyses consisted of all vaccinated participants who had safety follow-up data.

Noninjection-site rash Day 1 through Day 42 postvaccination was reported by the participant to the investigator and confirmed to be zosteriform rash by the study physician and polymerase chain reaction (PCR).

Outcome measures

Measure	Zoster Vaccine Higher Potency n=459 Participants Higher potency Zoster vaccine (approximately 207,000 plaque-forming units \[PFU\]), 1 subcutaneous 0.65 mL injection	Zoster Vaccine Lower Potency n=234 Participants Lower potency Zoster vaccine (approximately 58,000 PFU), 1 subcutaneous 0.65 mL injection
Number of Participants With Herpes Zoster (HZ) or HZ-like Rashes With zoster or rash, zosteriform	3 Participants	3 Participants
Number of Participants With Herpes Zoster (HZ) or HZ-like Rashes Without zoster or rash, zosteriform	456 Participants	231 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1-21 postvaccination

Population: The population for the safety analyses consisted of all vaccinated participants who had safety follow-up data. 5 participants in the Zoster Vaccine Higher Potency group and 3 participants in the Zoster Vaccine Lower Potency group were not included in this analysis since these participants were without a follow-up.

Maximum reported oral or equivalent temperature ≥101.0°F [≥38.3°C] was reported Day 1 through Day 21 postvaccination.

Outcome measures

Measure	Zoster Vaccine Higher Potency n=456 Participants Higher potency Zoster vaccine (approximately 207,000 plaque-forming units \[PFU\]), 1 subcutaneous 0.65 mL injection	Zoster Vaccine Lower Potency n=231 Participants Lower potency Zoster vaccine (approximately 58,000 PFU), 1 subcutaneous 0.65 mL injection
Number of Participants With Fevers ≥101.0°F [≥38.3°C] With max oral temp ≥101.0°F (≥38.3°C)	4 Participants	2 Participants
Number of Participants With Fevers ≥101.0°F [≥38.3°C] With max oral temp <101.0°F (<38.3°C)	452 Participants	229 Participants

Adverse Events

Zoster Vaccine Higher Potency

Serious events: 4 serious events

Other events: 296 other events

Deaths: 0 deaths

Zoster Vaccine Lower Potency

Serious events: 1 serious events

Other events: 141 other events

Deaths: 0 deaths

Serious adverse events

Measure	Zoster Vaccine Higher Potency n=459 participants at risk Higher potency Zoster vaccine (approximately 207,000 plaque-forming units \[PFU\]), 1 subcutaneous 0.65 mL injection	Zoster Vaccine Lower Potency n=234 participants at risk Lower potency Zoster vaccine (approximately 58,000 PFU), 1 subcutaneous 0.65 mL injection
Cardiac disorders Angina pectoris	0.22% 1/459 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.	0.00% 0/234 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.
Cardiac disorders Coronary artery disease	0.22% 1/459 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.	0.00% 0/234 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.
Gastrointestinal disorders Enteritis	0.22% 1/459 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.	0.00% 0/234 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer stage unspecified	0.00% 0/459 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.	0.43% 1/234 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.
Psychiatric disorders Depression	0.22% 1/459 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.	0.00% 0/234 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.

Other adverse events

Measure	Zoster Vaccine Higher Potency n=459 participants at risk Higher potency Zoster vaccine (approximately 207,000 plaque-forming units \[PFU\]), 1 subcutaneous 0.65 mL injection	Zoster Vaccine Lower Potency n=234 participants at risk Lower potency Zoster vaccine (approximately 58,000 PFU), 1 subcutaneous 0.65 mL injection
Nervous system disorders Headache	9.4% 43/459 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.	6.8% 16/234 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.
General disorders Injection Site Erythema	49.5% 227/459 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.	47.4% 111/234 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.
General disorders Injection Site Pain	47.3% 217/459 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.	38.9% 91/234 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.
General disorders Injection Site Pruritus	12.6% 58/459 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.	9.0% 21/234 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.
General disorders Injection Site Swelling	41.2% 189/459 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.	32.9% 77/234 • Day 1 - 42 postvaccination Daily temperature readings, injection-site adverse experiences, rashes, and other adverse experiences were recorded by the participant on a Vaccination Report Card which was reviewed 42 days after vaccination. Number of participants at risk included randomized participants who had follow-up after at least one dose of vaccination.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Results disclosure agreements

• Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER