Trial Outcomes & Findings for Immunogenicity and Safety Study of ZOSTAVAX Administered by Intramuscular or Subcutaneous Route to Participants Aged From 50 Years Old (V211-045) (NCT NCT01391546)

Results Overview

Blood samples taken at 4 weeks post vaccination to determine the geometric mean titre (GMT) of VZV antibodies via Glycoprotein Enzyme Linked Immunosorbent Assay (gpELISA).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

354 participants

Primary outcome timeframe

4 week post-vaccination

Results posted on

2019-01-09

Participant Flow

Participant milestones

Participant milestones
Measure	ZOSTAVAX Intramuscular (IM) Route Single dose of 0.65 mL via IM injection	ZOSTAVAX Subcutaneous (SC) Route Single dose of 0.65 mL via SC injection
Overall Study STARTED	177	177
Overall Study Vaccinated	176	177
Overall Study COMPLETED	176	177
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	ZOSTAVAX Intramuscular (IM) Route Single dose of 0.65 mL via IM injection	ZOSTAVAX Subcutaneous (SC) Route Single dose of 0.65 mL via SC injection
Overall Study History of Herpes Zoster (HZ)	1	0

Baseline Characteristics

One enrolled participant in IM arm withdrew prior to vaccination

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ZOSTAVAX Intramuscular (IM) Route n=177 Participants Single dose of 0.65 mL via IM injection	ZOSTAVAX Subcutaneous (SC) Route n=177 Participants Single dose of 0.65 mL via SC injection	Total n=354 Participants Total of all reporting groups
Age, Customized 50-59 years of age	81 Participants n=177 Participants	82 Participants n=177 Participants	163 Participants n=354 Participants
Age, Customized 60-69 years of age	56 Participants n=177 Participants	55 Participants n=177 Participants	111 Participants n=354 Participants
Age, Customized ≥70 years of age	40 Participants n=177 Participants	40 Participants n=177 Participants	80 Participants n=354 Participants
Sex: Female, Male Female	98 Participants n=177 Participants	97 Participants n=177 Participants	195 Participants n=354 Participants
Sex: Female, Male Male	79 Participants n=177 Participants	80 Participants n=177 Participants	159 Participants n=354 Participants
Age at Vaccination	62.6 Years of Age STANDARD_DEVIATION 8.3 • n=176 Participants • One enrolled participant in IM arm withdrew prior to vaccination	62.6 Years of Age STANDARD_DEVIATION 8.5 • n=177 Participants • One enrolled participant in IM arm withdrew prior to vaccination	62.6 Years of Age STANDARD_DEVIATION 8.4 • n=353 Participants • One enrolled participant in IM arm withdrew prior to vaccination

PRIMARY outcome

Timeframe: 4 week post-vaccination

Population: All randomised participants who had received the study vaccine, had at least one valid immunogenicity evaluation for VZV antibody and had post-vaccination data available for endpoint.

Blood samples taken at 4 weeks post vaccination to determine the geometric mean titre (GMT) of VZV antibodies via Glycoprotein Enzyme Linked Immunosorbent Assay (gpELISA).

Outcome measures

Outcome measures
Measure	ZOSTAVAX Intramuscular (IM) Route n=168 Participants Single dose of 0.65 mL via IM injection	ZOSTAVAX Subcutaneous (SC) Route n=173 Participants Single dose of 0.65 mL via SC injection
Geometric Mean Titre (GMT) of Varicella Zoster Virus (VZV) Antibodies 4 Weeks Post-vaccination	395.3 gpELISA units/mL Interval 350.6 to 445.6	391.7 gpELISA units/mL Interval 348.9 to 439.7

PRIMARY outcome

Timeframe: Pre-vaccination (Day 0) and 4 week post-vaccination

Population: All randomised participants who had received the study vaccine via IM route, had at least one valid immunogenicity evaluation for VZV antibody and had post-vaccination data available for endpoint.

Blood sample taken at predose (Day 0) and 4 weeks post vaccination to determine the geometric mean titre (GMT) of VZV antibodies via gpELISA. The GMFR was calculated as GMT Post-dose/GMT Pre-vaccination

Outcome measures

Outcome measures
Measure	ZOSTAVAX Intramuscular (IM) Route n=168 Participants Single dose of 0.65 mL via IM injection	ZOSTAVAX Subcutaneous (SC) Route Single dose of 0.65 mL via SC injection
Geometric Mean Fold Rise (GMFR) in VZV Antibody Titre: IM Route	2.7 Ratio Interval 2.4 to 3.0	—

SECONDARY outcome

Timeframe: Pre-vaccination (Day 0) and 4 week post-vaccination

Population: All randomised participants who had received the study vaccine via SC route, had at least one valid immunogenicity evaluation for VZV antibody and had post-vaccination data available for endpoint.

Blood sample taken at predose (Day 0) and 4 weeks post vaccination to determine the geometric mean titre (GMT) of VZV antibodies via gpELISA. The GMFR was calculated as GMT Post-vaccination/GMT Pre-vaccination

Outcome measures

Outcome measures
Measure	ZOSTAVAX Intramuscular (IM) Route n=172 Participants Single dose of 0.65 mL via IM injection	ZOSTAVAX Subcutaneous (SC) Route Single dose of 0.65 mL via SC injection
Geometric Mean Fold Rise (GMFR) in VZV Antibody Titre: SC Route	2.5 Ratio Interval 2.2 to 2.8	—

SECONDARY outcome

Timeframe: 4 week post-vaccination

Population: All randomised participants in the ELISPOT subset (predetermined protocol-defined sites) who had received the study vaccine and had valid post-vaccination data for endpoint.

Blood samples taken 4 weeks post-vaccination to determine the IFN-γ ELISPOT GMC's. Results were reported as ELISPOT count/10\^6 Peripheral Blood Mononuclear Cells (PBMC)

Outcome measures

Outcome measures
Measure	ZOSTAVAX Intramuscular (IM) Route n=103 Participants Single dose of 0.65 mL via IM injection	ZOSTAVAX Subcutaneous (SC) Route n=105 Participants Single dose of 0.65 mL via SC injection
Geometric Mean Count (GMCs) of VZV Interferon Gamma ((IFN-γ) Enzyme-Linked ImmunoSpot (ELISPOT) Antibodies	209.8 ELISPOT count/10^6 PBMC Interval 175.2 to 251.3	195.7 ELISPOT count/10^6 PBMC Interval 161.9 to 236.6

SECONDARY outcome

Timeframe: Pre-vaccination (Day 0) and 4 week post-vaccination

Population: All randomised participants in the ELISPOT subset (predetermined protocol-defined sites) who had received the study vaccine and had valid pre- and post-vaccination data for endpoint.

Blood samples taken pre-vaccination and 4 weeks post-vaccination to determine the IFN-γ ELISPOT GMFR.

Outcome measures

Outcome measures
Measure	ZOSTAVAX Intramuscular (IM) Route n=93 Participants Single dose of 0.65 mL via IM injection	ZOSTAVAX Subcutaneous (SC) Route n=90 Participants Single dose of 0.65 mL via SC injection
Geometric Mean Fold Rise (GMFR) of IFN-γ ELISPOT Antibodies	3.3 Ratio Interval 2.8 to 3.9	3.4 Ratio Interval 2.7 to 4.3

SECONDARY outcome

Timeframe: up to 28 days after vaccination

Population: All vaccinated participants who had follow-up safety data.

Participants entered data into daily diary card regarding previously identified possible injection site reactions of erythema, injection site swelling or injection site pain for 1st 4 days post-vaccination. Additionally, injection site reactions not prompted on diary card (unsolicited) were collected up 28 days post-vaccination. All injection site reactions (solicited or unsolicited) were recorded.

Outcome measures

Outcome measures
Measure	ZOSTAVAX Intramuscular (IM) Route n=176 Participants Single dose of 0.65 mL via IM injection	ZOSTAVAX Subcutaneous (SC) Route n=177 Participants Single dose of 0.65 mL via SC injection
Percentage of Participants Who Report at Least 1 Injection-site Adverse Reaction	34.1 Percentage of Participants Interval 27.1 to 41.6	64.4 Percentage of Participants Interval 56.9 to 71.4

SECONDARY outcome

Timeframe: up to Day 28 after vaccination

Population: All vaccinated participants who had follow-up safety data.

An adverse event (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Adverse events that were considered systemic (not localized) were summarized. These events included rashes of interest: i.e. Varicella, Varicella-like rashes, Herpes zoster or shingles and Herpes zoster-like rashes and other systemic adverse events.

Outcome measures

Outcome measures
Measure	ZOSTAVAX Intramuscular (IM) Route n=176 Participants Single dose of 0.65 mL via IM injection	ZOSTAVAX Subcutaneous (SC) Route n=177 Participants Single dose of 0.65 mL via SC injection
Percentage of Participants Who Report at Least 1 Systemic Adverse Event	23.3 Percentage of Participants Interval 17.3 to 30.2	22.6 Percentage of Participants Interval 16.7 to 29.5

SECONDARY outcome

Timeframe: up to 35 days after vaccination

A serious adverse event (SAE) is any adverse event that results in death, is life threatening, results in a persistent or significant disability/incapacity, results in hospitalization or prolongs an existing hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose, or is considered an "other important medical event" based on medical judgement. The percentage of participants who reported an SAE within 35 days of vaccination were recorded.

Outcome measures

Outcome measures
Measure	ZOSTAVAX Intramuscular (IM) Route n=176 Participants Single dose of 0.65 mL via IM injection	ZOSTAVAX Subcutaneous (SC) Route n=177 Participants Single dose of 0.65 mL via SC injection
Percentage of Participants Who Report at Least 1 Serious Adverse Event	0.6 Percentage of Participants Interval to 3.1	1.1 Percentage of Participants

Adverse Events

ZOSTAVAX Intramuscular (IM) Route

Serious events: 1 serious events

Other events: 59 other events

Deaths: 0 deaths

ZOSTAVAX Subcutaneous (SC) Route

Serious events: 2 serious events

Other events: 112 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ZOSTAVAX Intramuscular (IM) Route n=176 participants at risk Single dose of 0.65 mL via IM injection	ZOSTAVAX Subcutaneous (SC) Route n=177 participants at risk Single dose of 0.65 mL via SC injection
General disorders Hernia obstructive	0.57% 1/176 • Number of events 1 • up to 35 days Safety population included all participants who received vaccine and had safety follow-up data available.	0.00% 0/177 • up to 35 days Safety population included all participants who received vaccine and had safety follow-up data available.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/176 • up to 35 days Safety population included all participants who received vaccine and had safety follow-up data available.	0.56% 1/177 • Number of events 1 • up to 35 days Safety population included all participants who received vaccine and had safety follow-up data available.
Vascular disorders Deep vein thrombosis	0.00% 0/176 • up to 35 days Safety population included all participants who received vaccine and had safety follow-up data available.	0.56% 1/177 • Number of events 1 • up to 35 days Safety population included all participants who received vaccine and had safety follow-up data available.

Other adverse events

Other adverse events
Measure	ZOSTAVAX Intramuscular (IM) Route n=176 participants at risk Single dose of 0.65 mL via IM injection	ZOSTAVAX Subcutaneous (SC) Route n=177 participants at risk Single dose of 0.65 mL via SC injection
General disorders Injection site erythema	16.5% 29/176 • Number of events 29 • up to 35 days Safety population included all participants who received vaccine and had safety follow-up data available.	53.1% 94/177 • Number of events 94 • up to 35 days Safety population included all participants who received vaccine and had safety follow-up data available.
General disorders Injection site pain	26.1% 46/176 • Number of events 46 • up to 35 days Safety population included all participants who received vaccine and had safety follow-up data available.	39.5% 70/177 • Number of events 70 • up to 35 days Safety population included all participants who received vaccine and had safety follow-up data available.
General disorders Injection site pruritus	1.7% 3/176 • Number of events 3 • up to 35 days Safety population included all participants who received vaccine and had safety follow-up data available.	6.2% 11/177 • Number of events 11 • up to 35 days Safety population included all participants who received vaccine and had safety follow-up data available.
General disorders Injection site swelling	13.6% 24/176 • Number of events 24 • up to 35 days Safety population included all participants who received vaccine and had safety follow-up data available.	37.9% 67/177 • Number of events 67 • up to 35 days Safety population included all participants who received vaccine and had safety 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 Investigators must first obtain written consent from Sponsor. If consent is given, all abstracts manuscripts, texts, or presentation, etc. will be sent to Sponsor for review and approval prior to their publication or presentation. Sponsor shall have sixty days to review these documents and may refuse to give its consent in part or whole for confidential reasons (including but not limited to intellectual property rights, whether patentable or not).
Publication restrictions are in place

Restriction type: OTHER