A Study to Evaluate the Safety and Immunogenicity of Inactivated Varicella-Zoster Virus (VZV) Vaccine in Adults With Hematologic Malignancies (HM) Receiving Treatment With Anti-Cluster of Differentiation (CD) 20 Monoclonal Antibodies (V212-013)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01460719
• Collaborator: (none)
• Enrollment: 80
• Arm: 1
• Actual Duration (Months): 8

Study Details

Study Description

Brief Summary

An open-label, multicenter study to evaluate the safety and immunogenicity of inactivated VZV vaccine (V212) in participants with hematologic malignancies (HM) who are currently receiving anti-CD20 monoclonal antibodies. The primary hypothesis is that vaccination with V212 vaccine will elicit significant VZV-specific immune responses at ~28 days after vaccination 4. The statistical criterion for significance requires that the lower bound of the 2-sided 90% confidence interval of the geometric mean fold rise in immune response in V212 recipients is

1.0.

Condition or Disease	Intervention/Treatment	Phase
Herpes Zoster	Biological: V212	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase I, Open-Label, Multicenter Clinical Trial to Evaluate the Safety and Immunogenicity of V212/Inactivated Varicella-Zoster Virus (VZV) Vaccine in Adults With Hematologic Malignancies Receiving Treatment With Anti-CD20 Monoclonal Antibodies
• Actual Study Start Date: Jan 24, 2012
• Actual Primary Completion Date: Sep 25, 2012
• Actual Study Completion Date: Sep 25, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: V212 Participants receive V212 as a 0.5 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose.	Biological: V212; V212 viral antigen for HZ; Other Names: Inactivated Varicella-Zoster (VZV) vaccine

Outcome Measures

Primary Outcome Measures

1. Geometric Mean Fold Rise (GMFR) of the VZV-specific Immune Responses Measured by VZV Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISPOT) [Prevaccination (Day 1) and ~28 days after Vaccination 4 (~Day 118)]

   The VZV ELISPOT assay detects IFN-γ-secreting, VZV-specific cells from peripheral blood mononuclear cells (PBMCs). The unit of measure of the assay is ELISPOT cell count / 10^6 PBMCs, and is expressed as geometric mean count (GMC). The GMFR is GMC at ~28 days after Vaccination 4 / GMC on Day 1.

2. Percentage of Participants With an Adverse Event [Up to ~28 days after Vaccination 4 (~Day 118)]

   An adverse experience (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 study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the product is also an adverse experience. The percentage of participants with any AE was summarized.

3. Percentage of Participants With an Injection-site Adverse Event [Up to 5 days after any vaccination]

   An adverse experience (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 study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the product is also an adverse experience. The percentage of participants with any injection-site AE was summarized.

4. Percentage of Participants With a Systemic Adverse Event [Up to ~28 days after Vaccination 4 (~Day 118)]

   An adverse experience (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 study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the product is also an adverse experience. The percentage of participants with any systemic AE was summarized.

5. Percentage of Participants With a Serious Adverse Event [Up to ~28 days after Vaccination 4 (~Day 118)]

   A serious AE (SAE) is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs an inpatient hospitalization, is a congenital anomaly or birth defect, is an overdose, is a cancer, or is another important medical event. The percentage of participants with any SAE was summarized.

6. Percentage of Participants With a Vaccine-related Serious Adverse Event [Up to ~28 days after Vaccination 4 (~Day 118)]

   A serious AE (SAE) is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs an inpatient hospitalization, is a congenital anomaly or birth defect, is an overdose, is a cancer, or is another important medical event. The percentage of participants with any SAE that was deemed by the investigator to be possibly, probably, or definitely related to study vaccine was summarized.

7. Percentage of Participants With Study Vaccination Withdrawn Due to an Adverse Event [Up to Vaccination 4 (~Day 90)]

   An 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 study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the product is also an adverse experience. The percentage of participants with study vaccine withdrawn due to an AE was summarized.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosed with a HM and is receiving treatment with anti-CD20 monoclonal antibodies and is not likely to undergo hematopoietic cell transplant (HCT).

• Has a predicted life expectancy of ≥ 12 months.

• Has prior history of varicella or antibodies to VZV due to exposure to the disease in a country where the disease is common.

• All female participants of childbearing potential must have a negative serum or urine pregnancy test.

Exclusion Criteria:

• A history of allergic reaction to any vaccine component (including gelatin) or an anaphylactic/anaphylactoid reaction to neomycin.

• Prior history of HZ within 1 year of enrollment.

• Prior receipt of any varicella or zoster vaccine.

• Participant is pregnant or breastfeeding or expecting to conceive within the period of 2 weeks prior to enrollment throughout 6 months after last vaccination dose.

• Any live virus vaccine administered or scheduled in the period from 4 weeks prior to Dose 1 through 28 days postvaccination dose 4.

• Any inactivated vaccine administered or scheduled within the period from 7 days prior to, through 7 days following, any dose of study vaccine.

• Participant is currently participating or has participated in a study with an investigational anti-CD20 monoclonal antibody within 3 months of signing informed consent.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT01460719
• Other Study ID Numbers: V212-013; V212-013; 2011-003153-25
• First Posted: Oct 27, 2011
• Last Update Posted: Mar 11, 2019
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Herpes Zoster; Chickenpox; Hematologic Neoplasms; Vaccines

Study Results

Participant Flow

Recruitment Details	A total of 88 participants were screened and 80 were enrolled.

Arm/Group Title	V212
Arm/Group Description	Participants received V212 as a 0.5 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose
Period Title: Overall Study
STARTED	80
Vaccination 1 (Day 1)	80
Vaccination 2 (~Day 30)	78
Vaccination 3 (~Day 60)	78
Vaccination 4 (~Day 90)	78
COMPLETED	78
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	V212
Arm/Group Description	Participants received V212 as a 0.5 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose
Overall Participants	80
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.0 (11.3)
Sex: Female, Male (Count of Participants)
Female	43 53.8%
Male	37 46.3%

Outcome Measures

1. Primary Outcome

Title	Geometric Mean Fold Rise (GMFR) of the VZV-specific Immune Responses Measured by VZV Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISPOT)
Description	The VZV ELISPOT assay detects IFN-γ-secreting, VZV-specific cells from peripheral blood mononuclear cells (PBMCs). The unit of measure of the assay is ELISPOT cell count / 10^6 PBMCs, and is expressed as geometric mean count (GMC). The GMFR is GMC at ~28 days after Vaccination 4 / GMC on Day 1.
Time Frame	Prevaccination (Day 1) and ~28 days after Vaccination 4 (~Day 118)

Outcome Measure Data

Analysis Population Description

Vaccinated participants having valid results at Baseline (Day 1) and/or at ~28 days after Vaccination 4.

Arm/Group Title	V212
Arm/Group Description	Participants received V212 as a 0.5 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose
Measure Participants	78
Geometric Mean (90% Confidence Interval) [Ratio]	4.34

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	V212
	Comments
	Type of Statistical Test	Other
	Comments	The statistical criterion for significance requires that the lower bound of the 2-sided 90% confidence interval of the GMFR is >1.0.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Single longitudinal regression model
	Comments	Adjustments made for pre-vaccination values

2. Primary Outcome

Title	Percentage of Participants With an Adverse Event
Description	An adverse experience (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 study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the product is also an adverse experience. The percentage of participants with any AE was summarized.
Time Frame	Up to ~28 days after Vaccination 4 (~Day 118)

Outcome Measure Data

Analysis Population Description

All enrolled participants

Arm/Group Title	V212
Arm/Group Description	Participants received V212 as a 0.5 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose
Measure Participants	80
Number [Percentage of participants]	85.0 106.3%

3. Primary Outcome

Title	Percentage of Participants With an Injection-site Adverse Event
Description	An adverse experience (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 study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the product is also an adverse experience. The percentage of participants with any injection-site AE was summarized.
Time Frame	Up to 5 days after any vaccination

Outcome Measure Data

Analysis Population Description

All enrolled participants

Arm/Group Title	V212
Arm/Group Description	Participants received V212 as a 0.5 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose
Measure Participants	80
Number [Percentage of participants]	43.8 54.8%

4. Primary Outcome

Title	Percentage of Participants With a Systemic Adverse Event
Description	An adverse experience (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 study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the product is also an adverse experience. The percentage of participants with any systemic AE was summarized.
Time Frame	Up to ~28 days after Vaccination 4 (~Day 118)

Outcome Measure Data

Analysis Population Description

All enrolled participants

Arm/Group Title	V212
Arm/Group Description	Participants received V212 as a 0.5 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose
Measure Participants	80
Number [Percentage of participants]	73.8 92.3%

5. Primary Outcome

Title	Percentage of Participants With a Serious Adverse Event
Description	A serious AE (SAE) is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs an inpatient hospitalization, is a congenital anomaly or birth defect, is an overdose, is a cancer, or is another important medical event. The percentage of participants with any SAE was summarized.
Time Frame	Up to ~28 days after Vaccination 4 (~Day 118)

Outcome Measure Data

Analysis Population Description

All enrolled participants

Arm/Group Title	V212
Arm/Group Description	Participants received V212 as a 0.5 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose
Measure Participants	80
Number [Percentage of participants]	15.0 18.8%

6. Primary Outcome

Title	Percentage of Participants With a Vaccine-related Serious Adverse Event
Description	A serious AE (SAE) is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs an inpatient hospitalization, is a congenital anomaly or birth defect, is an overdose, is a cancer, or is another important medical event. The percentage of participants with any SAE that was deemed by the investigator to be possibly, probably, or definitely related to study vaccine was summarized.
Time Frame	Up to ~28 days after Vaccination 4 (~Day 118)

Outcome Measure Data

Analysis Population Description

All enrolled participants

Arm/Group Title	V212
Arm/Group Description	Participants received V212 as a 0.5 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose
Measure Participants	80
Number [Percentage of participants]	1.3 1.6%

7. Primary Outcome

Title	Percentage of Participants With Study Vaccination Withdrawn Due to an Adverse Event
Description	An 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 study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the product is also an adverse experience. The percentage of participants with study vaccine withdrawn due to an AE was summarized.
Time Frame	Up to Vaccination 4 (~Day 90)

Outcome Measure Data

Analysis Population Description

All enrolled participants

Arm/Group Title	V212
Arm/Group Description	Participants received V212 as a 0.5 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose
Measure Participants	80
Number [Percentage of participants]	1.3 1.6%

Adverse Events

Time Frame	Up to Day 140
Adverse Event Reporting Description	All participants who received at least one dose of V212
Arm/Group Title	V212
Arm/Group Description	Participants received V212 as a 0.5 mL subcutaneous injection in a four-dose regimen, approximately 30 days apart, preferably in the deltoid area of the arm, alternating arms for each dose
All Cause Mortality
	V212
	Affected / at Risk (%)	# Events
Total	1/80 (1.3%)
Serious Adverse Events
	V212
	Affected / at Risk (%)	# Events
Total	12/80 (15%)
Blood and lymphatic system disorders
Febrile neutropenia	4/80 (5%)	4
Neutropenia	2/80 (2.5%)	2
Gastrointestinal disorders
Diarrhoea	1/80 (1.3%)	1
Nausea	1/80 (1.3%)	1
General disorders
Pyrexia	1/80 (1.3%)	1
Infections and infestations
Candidiasis	1/80 (1.3%)	1
Pneumonia	2/80 (2.5%)	2
Salmonellosis	1/80 (1.3%)	1
Injury, poisoning and procedural complications
Subdural haematoma	1/80 (1.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hodgkin's disease	1/80 (1.3%)	1
Oesophageal squamous cell carcinoma stage 0	1/80 (1.3%)	1
Nervous system disorders
Convulsion	1/80 (1.3%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/80 (1.3%)	1
Other (Not Including Serious) Adverse Events
	V212
	Affected / at Risk (%)	# Events
Total	67/80 (83.8%)
Blood and lymphatic system disorders
Anaemia	2/80 (2.5%)	2
Leukocytosis	1/80 (1.3%)	1
Lymphadenopathy	1/80 (1.3%)	1
Neutropenia	6/80 (7.5%)	7
Pancytopenia	1/80 (1.3%)	1
Ear and labyrinth disorders
Ear pain	1/80 (1.3%)	1
Vertigo	1/80 (1.3%)	1
Eye disorders
Conjunctivitis	1/80 (1.3%)	1
Gastrointestinal disorders
Abdominal distension	1/80 (1.3%)	1
Abdominal pain	2/80 (2.5%)	2
Abdominal pain upper	1/80 (1.3%)	1
Aphthous stomatitis	1/80 (1.3%)	1
Diarrhoea	10/80 (12.5%)	13
Dyspepsia	2/80 (2.5%)	2
Gastric ulcer	1/80 (1.3%)	1
Gastrointestinal disorder	1/80 (1.3%)	1
Glossodynia	1/80 (1.3%)	1
Lip blister	1/80 (1.3%)	2
Nausea	4/80 (5%)	5
Pancreatitis acute	1/80 (1.3%)	1
Rectal haemorrhage	1/80 (1.3%)	1
Stomatitis	1/80 (1.3%)	1
Toothache	1/80 (1.3%)	1
General disorders
Chest pain	2/80 (2.5%)	2
Chills	2/80 (2.5%)	2
Fatigue	4/80 (5%)	5
Feeling hot	1/80 (1.3%)	2
Injection site erythema	25/80 (31.3%)	54
Injection site haematoma	2/80 (2.5%)	2
Injection site movement impairment	1/80 (1.3%)	2
Injection site pain	26/80 (32.5%)	57
Injection site paraesthesia	1/80 (1.3%)	1
Injection site pruritus	5/80 (6.3%)	9
Injection site rash	2/80 (2.5%)	2
Injection site swelling	21/80 (26.3%)	49
Malaise	1/80 (1.3%)	1
Mucosal dryness	1/80 (1.3%)	1
Oedema peripheral	2/80 (2.5%)	2
Pain	1/80 (1.3%)	1
Pyrexia	20/80 (25%)	27
Spinal pain	1/80 (1.3%)	1
Hepatobiliary disorders
Hepatic cyst	1/80 (1.3%)	1
Infections and infestations
Acariasis	1/80 (1.3%)	1
Anal abscess	1/80 (1.3%)	1
Bronchitis	2/80 (2.5%)	2
Cystitis	1/80 (1.3%)	1
Ear infection	2/80 (2.5%)	2
Folliculitis	1/80 (1.3%)	1
Localised infection	1/80 (1.3%)	1
Nasopharyngitis	3/80 (3.8%)	3
Oral candidiasis	1/80 (1.3%)	1
Oral herpes	1/80 (1.3%)	1
Pneumonia	1/80 (1.3%)	1
Rhinitis	1/80 (1.3%)	1
Sinusitis	3/80 (3.8%)	3
Trichophytosis	1/80 (1.3%)	1
Upper respiratory tract infection	3/80 (3.8%)	3
Urinary tract infection	1/80 (1.3%)	1
Viral tracheitis	1/80 (1.3%)	1
Vulvovaginal candidiasis	1/80 (1.3%)	1
Vulvovaginal mycotic infection	1/80 (1.3%)	1
Injury, poisoning and procedural complications
Arthropod bite	6/80 (7.5%)	10
Excoriation	1/80 (1.3%)	1
Laceration	1/80 (1.3%)	1
Post-traumatic pain	1/80 (1.3%)	1
Investigations
Weight decreased	1/80 (1.3%)	1
Metabolism and nutrition disorders
Decreased appetite	1/80 (1.3%)	1
Dehydration	1/80 (1.3%)	1
Hypercholesterolaemia	1/80 (1.3%)	1
Hyperuricaemia	1/80 (1.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	3/80 (3.8%)	3
Back pain	4/80 (5%)	5
Bone pain	3/80 (3.8%)	3
Bursitis	1/80 (1.3%)	1
Jaw disorder	1/80 (1.3%)	1
Musculoskeletal pain	1/80 (1.3%)	1
Musculoskeletal stiffness	1/80 (1.3%)	2
Myalgia	4/80 (5%)	7
Pain in extremity	2/80 (2.5%)	4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma	1/80 (1.3%)	1
Lung neoplasm	1/80 (1.3%)	1
Nervous system disorders
Carotid artery stenosis	1/80 (1.3%)	1
Dizziness	1/80 (1.3%)	1
Headache	7/80 (8.8%)	9
Hypoaesthesia	2/80 (2.5%)	3
Migraine	1/80 (1.3%)	1
Motor dysfunction	1/80 (1.3%)	1
Neuropathy peripheral	1/80 (1.3%)	1
Paraesthesia	1/80 (1.3%)	1
Peripheral motor neuropathy	1/80 (1.3%)	1
Peripheral sensory neuropathy	1/80 (1.3%)	1
Psychiatric disorders
Hallucination, auditory	1/80 (1.3%)	1
Insomnia	1/80 (1.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	6/80 (7.5%)	6
Dyspnoea	2/80 (2.5%)	2
Epistaxis	1/80 (1.3%)	1
Oropharyngeal pain	6/80 (7.5%)	8
Pneumonitis	1/80 (1.3%)	1
Productive cough	1/80 (1.3%)	1
Pulmonary granuloma	1/80 (1.3%)	1
Sinus congestion	1/80 (1.3%)	1
Skin and subcutaneous tissue disorders
Ecchymosis	1/80 (1.3%)	1
Pain of skin	1/80 (1.3%)	1
Papule	1/80 (1.3%)	1
Pruritus	3/80 (3.8%)	5
Rash	6/80 (7.5%)	7
Rash pruritic	1/80 (1.3%)	2
Rash vesicular	5/80 (6.3%)	5
Rosacea	1/80 (1.3%)	2
Skin burning sensation	1/80 (1.3%)	1
Skin discolouration	1/80 (1.3%)	1
Skin lesion	1/80 (1.3%)	1
Vascular disorders
Peripheral coldness	1/80 (1.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.