V212-011

Merck Sharp & Dohme Corp.

2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

No

No

No

Final

11 Apr 2017

No

Yes

11 Apr 2017

No

This is a randomized, double-blind, placebo-controlled study to assess the safety and tolerability of V212 when administered to adults with solid tumor malignancy (STM) receiving chemotherapy and to assess the impact of V212 on the development of herpes zoster (HZ) in adults with STM receiving chemotherapy. The primary hypothesis is that vaccination with V212 will reduce the incidence of HZ compared with placebo in adults with STM (lower bound of the 97.5% {one-sided α=0.0125} confidence interval [CI] for the estimated vaccine efficacy in adults with STM be >25%). Participants with hematologic malignancy (HM) were also enrolled and were to be originally included in the primary and secondary objectives and analyses. After an interim analysis demonstrated clear evidence of futility of V212 in the HM population, enrollment of this population was stopped and all HM-related objectives and analyses were made exploratory and are not reported in this record.

This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.

24 Jun 2011

No

Yes

Slovakia: 18

South Africa: 9

Spain: 86

Taiwan: 109

Thailand: 88

Turkey: 68

United Kingdom: 21

United States: 2594

Jordan: 12

Argentina: 35

Australia: 47

Austria: 55

Belgium: 28

Brazil: 119

Bulgaria: 75

Canada: 207

Chile: 152

Colombia: 261

Croatia: 41

Czech Republic: 22

Ecuador: 16

Estonia: 13

France: 90

Germany: 108

Greece: 115

Honduras: 142

Hong Kong: 30

Italy: 48

Korea, Republic of: 16

Lebanon: 89

Lithuania: 9

Mexico: 67

New Zealand: 13

Panama: 9

Peru: 183

Philippines: 22

Romania: 132

Russian Federation: 132

Saudi Arabia: 12

Singapore: 12

5305

861

0

0

0

0

0

0

3335

1913

57

Overall Study (overall period)

Randomised - controlled

Yes

V212

Powder and solution for solution for injection

Subcutaneous use

V212 viral antigen for HZ, 0.5 mL subcutaneous (SC) injection per dose, in a four dose regimen, approximately 30 days apart.

V212

Powder and solution for solution for injection

Subcutaneous use

V212 viral antigen for HZ, 0.5 mL SC injection per dose, in a four dose regimen, approximately 30 days apart.

Placebo

Powder and solution for solution for injection

Subcutaneous use

Vaccine stabilizer for V212 with no virus antigen, 0.5 mL SC injection per dose, in a four dose regimen, approximately 30 days apart.

Placebo

Powder and solution for solution for injection

Subcutaneous use

Vaccine stabilizer for V212 with no virus antigen, 0.5 mL SC injection per dose, in a four dose regimen, approximately 30 days apart.

V212-STM

V212-HM

Placebo-STM

Placebo-HM

V212-STM

V212-HM

Placebo-STM

Placebo-HM

Clinical criteria for suspected HZ cases were the development of a papular or vesicular rash with a dermatomal or generalized distribution, or in the absence of a rash, clinical suspicion of VZV infection with or without the detection of VZV in diagnostic specimens from blood, cerebrospinal fluid, lung, liver, or other organ. All suspected cases of HZ were subjected to adjudication by the Clinical Adjudication Committee (CAC). Case confirmation was based on skin lesion polymerase chain reaction, if available, or by adjudication of the clinical case description by the CAC, conducted according to the CAC Standard Operations Procedure. This analysis was based on the Modified Intent-to-Treat (MITT) population. The MITT population for this outcome measure included all randomized participants in the STM population who received at least one dose of vaccination. This endpoint was exploratory for the HM population, therefore that group was not included in this analysis.

Primary

Up to approximately 5 years

Vaccine efficacy was calculated as 1 minus the hazard ratio of HZ in the V212 group versus the placebo group. The success criterion for vaccine efficacy required that the lower bound of the 97.5% Confidence Interval (CI) be >0.25.

V212-STM v Placebo-STM

2678

Pre-specified

0.636

2-sided

An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, is a cancer, is an overdose, or is another important medical event. The analysis population included all participants who received ≥1 dose of vaccination or placebo and had safety follow-up. Three participants in the STM population were cross-treated, these participants were excluded from the safety analyses. This endpoint was exploratory for the HM population, therefore that group was not included in this analysis.

Primary

Up to 28 days after vaccination 4 (up to approximately 118 days)

V212-STM v Placebo-STM

2668

Pre-specified

1.4

2-sided

Moderate to severe HZ-associated pain was defined as 2 or more occurrences of a score of 3 or greater (0-to-10 scale, where 0 is no pain and 10 is pain as bad as you can imagine) on the Zoster Brief Pain Inventory (ZBPI) at any time from HZ onset through the end of the 6 month HZ-follow-up period. This analysis was based on the MITT population. The MITT population for this outcome measure included all randomized participants in the STM population who received at least one dose of vaccination. This endpoint was exploratory for the HM population, therefore that group was not included in this analysis.

Secondary

Up to 6 months after onset of HZ (up to approximately 5 years)

Vaccine efficacy was calculated as 1 minus the hazard ratio of HZ in the V212 group versus the placebo group. The success criterion for vaccine efficacy required that the lower bound of the 95% CI be >0.25.

V212-STM v Placebo-STM

2678

Pre-specified

0.771

2-sided

The composite efficacy endpoint of the incidence of HZ complications was defined as the occurrence of any of the following during the study: hospitalization or prolongation of hospitalization due to HZ, disseminated HZ (including disseminated HZ rash or VZV viremia), visceral HZ, ophthalmic HZ, neurological impairment due to HZ, or administration of intravenous acyclovir therapy for treatment of HZ. This analysis was based on the MITT population. The MITT population for this outcome measure included all randomized participants in the STM population who received at least one dose of vaccination. This endpoint was exploratory for the HM population, therefore that group was not included in this analysis.

Secondary

Up to 6 months after onset of HZ (up to approximately 5 years)

Vaccine efficacy was calculated as 1 minus the hazard ratio of HZ in the V212 group versus the placebo group. The success criterion for vaccine efficacy required that the lower bound of the 95% CI be >0.25.

V212-STM v Placebo-STM

2678

Pre-specified

0.874

2-sided

Postherpetic Neuralgia (PHN) was defined as pain in the area of the HZ rash with pain in the last 24 hours scored as 3 or greater (on a 0 to 10 scale, where 0 is no pain and 10 is pain as bad as you can imagine) on the ZBPI that persists or appears greater than or equal to 90 days after HZ rash onset. This analysis was based on the MITT population. The MITT population for this outcome measure included all randomized participants in the STM population who received at least one dose of vaccination. This endpoint was exploratory for the HM population, therefore that group was not included in this analysis.

Secondary

Up to 6 months after onset of HZ (up to approximately 5 years)

Vaccine efficacy was calculated as 1 minus the hazard ratio of HZ in the V212 group versus the placebo group. The success criterion for vaccine efficacy required that the lower bound of the 95% CI be >0.25.

V212-STM v Placebo-STM

2678

Pre-specified

0.746

2-sided

An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, is a cancer, is an overdose, or is another important medical event.

Other pre-specified

Up to 28 days after vaccination 4 (up to approximately 118 days)

V212-STM v Placebo-STM

2668

Pre-specified

0.5

2-sided

Adverse events were collected up to approximately 5 years after vaccination 1.

The All Subjects as Treated population included all participants who received ≥1 dose of vaccination or placebo and had safety follow-up. Three participants in the STM population were cross-treated, these participants were excluded from the safety analyses.

19.1

V212-STM

V212-HM

Placebo-STM

Placebo-HM