Trial Outcomes & Findings for A Study to Evaluate Immunity to Varicella Zoster Virus After Immunization With V212 Vaccine or Zostavax (V212-003) (NCT NCT00886613)

Results Overview

Participants were given the VZV skin test prior to vaccination. For the baseline VZV skin test, they were administered VZV skin test reagent and saline in opposite arms, and assessed for a skin reaction around the injection site. The skin reaction assessed was erythema (redness of skin) and induration (palpable, raised, hardened area) around the injection site, which was marked with a ball point pen. The longest dimension to the closest 1 mm was measured. Participants with a reaction measure \< 5mm for saline and \< 5mm for the VZV antigen were considered to have a negative baseline skin test.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

120 participants

Primary outcome timeframe

48 hours following administration of the baseline skin test

Results posted on

2015-10-06

Participant Flow

The study was performed in 2 parts - Part A and Part B, with a total of 120 participants.

In Part A, 42 participants received a baseline VZV Skin Test which was evaluated 48 and 72 post administration, and these participants were included in the analysis for Part B. All Participants were randomized to receive V212, Zostavax™ or placebo.

Participant milestones

Participant milestones
Measure	V212 Participants randomized to receive two subcutaneous injections of 0.65 mL V212 (heat treated VZV Vaccine) administered at Day 1 and Day 31.	Zostavax™ Participants randomized to receive two subcutaneous injections of 0.65 mL Zostavax™ administered at Day 1 and Day 31.	Placebo Participants randomized to receive two subcutaneous injections of 0.65 mL of placebo administered at Day 1 and Day 31.
Overall Study STARTED	41	39	40
Overall Study COMPLETED	39	39	37
Overall Study NOT COMPLETED	2	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	V212 Participants randomized to receive two subcutaneous injections of 0.65 mL V212 (heat treated VZV Vaccine) administered at Day 1 and Day 31.	Placebo Participants randomized to receive two subcutaneous injections of 0.65 mL of placebo administered at Day 1 and Day 31.
Overall Study Protocol deviation (Part B)	1	0
Overall Study Lost to follow-up (Part B)	1	1
Overall Study Subject withdrew consent (Part A)	0	2

Baseline Characteristics

A Study to Evaluate Immunity to Varicella Zoster Virus After Immunization With V212 Vaccine or Zostavax (V212-003)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	V212 n=41 Participants Participants randomized to receive two subcutaneous injections of 0.65 mL V212 (heat treated VZV Vaccine) administered at Day 1 and Day 31.	Zostavax™ n=39 Participants Participants randomized to receive two subcutaneous injections of 0.65 mL Zostavax™ administered at Day 1 and Day 31.	Placebo n=40 Participants Participants randomized to receive two subcutaneous injections of 0.65 mL of placebo administered at Day 1 and Day 31.	Total n=120 Participants Total of all reporting groups
Age, Customized Between 60 and 88 years	41 participants n=5 Participants	39 participants n=7 Participants	40 participants n=5 Participants	120 participants n=4 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	26 Participants n=7 Participants	23 Participants n=5 Participants	74 Participants n=4 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	13 Participants n=7 Participants	17 Participants n=5 Participants	46 Participants n=4 Participants
Region of Enrollment United States	41 participants n=5 Participants	39 participants n=7 Participants	40 participants n=5 Participants	120 participants n=4 Participants

PRIMARY outcome

Timeframe: 48 hours following administration of the baseline skin test

Population: Participants enrolled in Part A with a negative reaction for saline.

Participants were given the VZV skin test prior to vaccination. For the baseline VZV skin test, they were administered VZV skin test reagent and saline in opposite arms, and assessed for a skin reaction around the injection site. The skin reaction assessed was erythema (redness of skin) and induration (palpable, raised, hardened area) around the injection site, which was marked with a ball point pen. The longest dimension to the closest 1 mm was measured. Participants with a reaction measure \< 5mm for saline and \< 5mm for the VZV antigen were considered to have a negative baseline skin test.

Outcome measures

Outcome measures
Measure	Part A Participants - VZV Skin Reaction (Baseline) n=39 Participants All 42 participants enrolled for part A were administered the VZV skin test and assessed for a skin reaction at baseline.	Part A Participants - VZV Skin Reaction (72 Hrs) All 42 participants enrolled for part A were administered the VZV skin test and assessed for a skin reaction after 72 hours.	Placebo Participants randomized to receive two subcutaneous injections of 0.65 mL of placebo administered at Day 1 and Day 31.
Number of Participants With a Negative VZV Skin Test at Baseline (Part A)	23 Participants	—	—

PRIMARY outcome

Timeframe: 48-72 hours after administration of skin test at 14-17 days postdose 2

Population: Per protocol population - participants with a negative baseline VZV Skin Test (\<5 mm skin reaction to both, saline and the VZV skin test reagent), and who did not have a protocol deviation that could interfere with the immune response to vaccine following two administrations of either ZOSTAVAX™, placebo, or V212

Number of participants with a positive VZV skin test after 2 vaccine doses was determined. Participants with a negative VZV skin test reaction at baseline were evaluated for VZV immunogenicity by a final VZV skin test administered 14 days after dose 2 of vaccination. For the VZV skin test participants were injected intradermally with the VZV skin test reagent, and reaction to the skin test was assessed after 48-72 hrs. A skin reaction (erythema and induration) around the injection site measuring \>= 5mm for the VZV antigen was considered a positive skin test.

Outcome measures

Outcome measures
Measure	Part A Participants - VZV Skin Reaction (Baseline) n=28 Participants All 42 participants enrolled for part A were administered the VZV skin test and assessed for a skin reaction at baseline.	Part A Participants - VZV Skin Reaction (72 Hrs) n=28 Participants All 42 participants enrolled for part A were administered the VZV skin test and assessed for a skin reaction after 72 hours.	Placebo n=25 Participants Participants randomized to receive two subcutaneous injections of 0.65 mL of placebo administered at Day 1 and Day 31.
Number of Healthy, Elderly, Immunocompetent Participants With a Positive VZV Skin Test After Administration of 2 Doses of V212 Vaccine (Part B)	15 Participants	15 Participants	12 Participants

SECONDARY outcome

Timeframe: 48 hours and 72 hours post administration of baseline skin test

Population: 42 participants enrolled in Part A

Prior to vaccination, participants were administered a baseline VZV skin test for which the skin test reagent and saline were injected in opposite arms. The skin reaction (erythema and induration) around the injection site was assessed at 48 hours and at 72 hours. The reaction was marked with a ball point pen and the longest dimension closest to 1 mm was measured. Participants with a reaction measure \< 5mm for saline and \< 5mm for the VZV antigen were defined as having a negative baseline skin test; and a measure of \>= 5mm for the VZV antigen were defined as having a positive skin test.

Outcome measures

Outcome measures
Measure	Part A Participants - VZV Skin Reaction (Baseline) n=42 Participants All 42 participants enrolled for part A were administered the VZV skin test and assessed for a skin reaction at baseline.	Part A Participants - VZV Skin Reaction (72 Hrs) n=42 Participants All 42 participants enrolled for part A were administered the VZV skin test and assessed for a skin reaction after 72 hours.	Placebo Participants randomized to receive two subcutaneous injections of 0.65 mL of placebo administered at Day 1 and Day 31.
VZV Skin Test Reactions at 48 and 72 Hours (Part A) Participants with a negative VZV skin test	24 Participants	25 Participants	—
VZV Skin Test Reactions at 48 and 72 Hours (Part A) Participants with a positive VZV skin test	18 Participants	17 Participants	—

SECONDARY outcome

Timeframe: 1-28 days post vaccination dose 1 and 1-28 days post vaccination dose 2

Population: Participants from Part B. One participant in the placebo group was not vaccinated and is not included in the analysis.

The number of participants with all serious and nonserious adverse events, and vaccine-related serious and nonserious adverse events, from 1-28 days post any vaccination dose was determined to assess safety. Non serious adverse events include injection-site adverse events as well as systemic adverse events post vaccination. Vaccine-related events include all events that were possibly, probably or definitely related to the vaccine according to the investigator. Participants with injection site adverse events due to administration of VZV skin tests are not included.

Outcome measures

Outcome measures
Measure	Part A Participants - VZV Skin Reaction (Baseline) n=41 Participants All 42 participants enrolled for part A were administered the VZV skin test and assessed for a skin reaction at baseline.	Part A Participants - VZV Skin Reaction (72 Hrs) n=39 Participants All 42 participants enrolled for part A were administered the VZV skin test and assessed for a skin reaction after 72 hours.	Placebo n=39 Participants Participants randomized to receive two subcutaneous injections of 0.65 mL of placebo administered at Day 1 and Day 31.
Number of Healthy Elderly Men and Women With Adverse Events Post Vaccination With V212 (Part B) One or more vaccine-related (VR) AE	12 Participants	24 Participants	9 Participants
Number of Healthy Elderly Men and Women With Adverse Events Post Vaccination With V212 (Part B) No adverse experiences (AE)	17 Participants	10 Participants	10 Participants
Number of Healthy Elderly Men and Women With Adverse Events Post Vaccination With V212 (Part B) One or more AE	22 Participants	26 Participants	19 Participants
Number of Healthy Elderly Men and Women With Adverse Events Post Vaccination With V212 (Part B) One or more injection-site AE	11 Participants	26 Participants	9 Participants
Number of Healthy Elderly Men and Women With Adverse Events Post Vaccination With V212 (Part B) One or more systemic AE	15 Participants	14 Participants	14 Participants
Number of Healthy Elderly Men and Women With Adverse Events Post Vaccination With V212 (Part B) One or more VR injection-site AE	11 Participants	22 Participants	8 Participants
Number of Healthy Elderly Men and Women With Adverse Events Post Vaccination With V212 (Part B) One or more VR systemic AE	1 Participants	5 Participants	2 Participants
Number of Healthy Elderly Men and Women With Adverse Events Post Vaccination With V212 (Part B) One or more SAE	0 Participants	0 Participants	0 Participants
Number of Healthy Elderly Men and Women With Adverse Events Post Vaccination With V212 (Part B) One or more VR SAE	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 1-5 days post administration of each VZV skin test

Population: Participants from Part B. One participant in the placebo group was not vaccinated and is not included in the analysis.

The number of participants with injection site adverse events due to the VZV skin test after administration of the VZV skin test antigen.

Outcome measures

Outcome measures
Measure	Part A Participants - VZV Skin Reaction (Baseline) n=41 Participants All 42 participants enrolled for part A were administered the VZV skin test and assessed for a skin reaction at baseline.	Part A Participants - VZV Skin Reaction (72 Hrs) n=39 Participants All 42 participants enrolled for part A were administered the VZV skin test and assessed for a skin reaction after 72 hours.	Placebo n=39 Participants Participants randomized to receive two subcutaneous injections of 0.65 mL of placebo administered at Day 1 and Day 31.
Number of Healthy Elderly Men and Women With Injection Site Adverse Events Post Administration of VZV Skin Tests (Part B)	36 Participants	36 Participants	28 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 48 hours following administration of the baseline skin test

Population: 42 participants enrolled in Part A

Participants were given the VZV skin test prior to vaccination. For the baseline VZV skin test, they were administered VZV skin test reagent and saline in opposite arms. The skin reaction (erythema and induration) to saline was marked with a ball point pen. The longest dimension to the closest 1 mm was measured. Participants with a reaction measure \< 5mm for saline had a negative reaction for saline, and measure \>= 5mm for saline had a positive reaction for saline at baseline.

Outcome measures

Outcome measures
Measure	Part A Participants - VZV Skin Reaction (Baseline) n=42 Participants All 42 participants enrolled for part A were administered the VZV skin test and assessed for a skin reaction at baseline.	Part A Participants - VZV Skin Reaction (72 Hrs) All 42 participants enrolled for part A were administered the VZV skin test and assessed for a skin reaction after 72 hours.	Placebo Participants randomized to receive two subcutaneous injections of 0.65 mL of placebo administered at Day 1 and Day 31.
Number of Participants With a Negative Reaction for Saline at Baseline (Part A) Negative reaction to saline	39 Participants	—	—
Number of Participants With a Negative Reaction for Saline at Baseline (Part A) Positive reaction to saline	2 Participants	—	—
Number of Participants With a Negative Reaction for Saline at Baseline (Part A) Participants with missing assessment	1 Participants	—	—

Adverse Events

V212

Serious events: 0 serious events

Other events: 36 other events

Deaths: 0 deaths

Zostavax™

Serious events: 0 serious events

Other events: 36 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	V212 n=41 participants at risk Participants randomized to receive two subcutaneous injections of 0.65 mL V212 (heat treated VZV Vaccine) administered at Day 1 and Day 31.	Zostavax™ n=39 participants at risk Participants randomized to receive two subcutaneous injections of 0.65 mL Zostavax™ administered at Day 1 and Day 31.	Placebo n=39 participants at risk Participants randomized to receive two subcutaneous injections of 0.65 mL of placebo administered at Day 1 and Day 31.
Nervous system disorders Headache	2.4% 1/41 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	5.1% 2/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	5.1% 2/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.
General disorders Injection site erythema (Vaccination)	26.8% 11/41 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	46.2% 18/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	17.9% 7/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.
General disorders Injection site erythema (Skin test)	87.8% 36/41 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	92.3% 36/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	71.8% 28/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.
General disorders Injection site induration (Vaccination)	14.6% 6/41 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	41.0% 16/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	10.3% 4/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.
General disorders Injection site induration (Skin test)	46.3% 19/41 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	46.2% 18/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	43.6% 17/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.
General disorders Injection site pain (Vaccination)	9.8% 4/41 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	53.8% 21/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	5.1% 2/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.
General disorders Injection site pain (Skin test)	12.2% 5/41 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	20.5% 8/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	5.1% 2/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.
General disorders Injection site pruritis (Vaccination)	4.9% 2/41 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	5.1% 2/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	0.00% 0/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.
Skin and subcutaneous tissue disorders Rash	0.00% 0/41 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	7.7% 3/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	2.6% 1/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.
Skin and subcutaneous tissue disorders Rash vesicular	0.00% 0/41 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	2.6% 1/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	5.1% 2/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.
Skin and subcutaneous tissue disorders Heat rash	0.00% 0/41 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	5.1% 2/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.	0.00% 0/39 • 1-28 days post any vaccine dose The analyzed population includes all vaccinated participants. One participant in the placebo group was not vaccinated and is not included in the analysis.

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 For multicenter studies, an investigator and his/her colleagues may publish their data independently subsequent to the multicenter publication. 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. SPONSOR review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER