Safety Study of ProQuad® rHA in Infants (V221-037)

An Open-label, Multi-centre Study of the Safety of a 2-dose Regimen of a Combined Measles, Mumps, Rubella and Varicella Live Vaccine (ProQuad®) Manufactured With Recombinant Human Albumin (rHA) When Administered to Children in Their Second Year of Life

Primary objective: To describe the safety profile of a second dose of ProQuad® manufactured with recombinant human albumin (rHA) when administered to children in their second year of life.

Secondary objectives: To describe the safety profile of a first dose of ProQuad® manufactured with rHA when administered to children in their second year of life.

Study Overview

• Status: Completed
• Conditions: Measles; Rubella; Mumps; Varicella
• Intervention / Treatment: Biological: ProQuad®

• Study Type: Interventional
• Enrollment (Actual): 3388
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 5 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy subject of either gender,
• Age from 12 to 22 months,
• Negative clinical history of infection with measles, mumps, rubella, varicella or zoster,
• Informed consent form signed by the parent(s) or by legal representative
• Parent(s) or legal representative able to attend all schedule visits with the subject and to understand and comply with the study procedures

Exclusion Criteria:

• Recent (≤ 3 days) history of febrile illness
• Prior receipt of measles, mumps, rubella and/or varicella vaccination, either alone or in any combination
• Recent (≤ 30 days) exposure to measles, mumps, rubella, varicella or zoster
• Prior known sensitivity/allergy to any component of the vaccine
• Severe chronic disease,
• Blood dyscrasias, leukaemia, lymphomas of any type, or other malignant neoplasms affecting the haematopoietic and lymphatic system
• Any severe thrombocytopenia or any other coagulation disorder that would contraindicate intramuscular injection
• Humoral or cellular immunodeficiency,
• Current immunosuppressive therapy
• Family history of congenital or hereditary immunodeficiency
• Hereditary problems of fructose intolerance
• Known personal history of encephalopathy, seizure disorder or progressive, evolving or unstable neurological condition,
• Known active tuberculosis
• Recent (≤ 2 days) tuberculin test or scheduled tuberculin test through Visit 3
• Receipt of immunoglobulins or blood-derived products in the past 150 days
• Receipt of an inactivated vaccine in the past 14 days
• Receipt of a live vaccine in the past 28 days
• Any medical condition which, in the opinion of the investigator, might interfere with the evaluation of study objectives
• Participation in another clinical study in the past 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ProQuad®; Healthy infants (12 to 22 months of age) received 2 doses of ProQuad® (Dose 1 on Day 1 and Dose 2 on Day 28 to 42) via subcutaneous injection into the deltoid muscle.	Biological: ProQuad®; ProQuad® manufactured with recombinant human albumin (rHA) is an investigational combined attenuated live virus vaccine for vaccination against measles, mumps, rubella and varicella viruses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing an Adverse Event (AE) After ProQuad® Dose 2	The percentage of participants experiencing an AE(s) for up to 28 days after the second ProQuad® injection was determined.	Up to Day 70 (up to 28 days after ProQuad® Dose 2)
Percentage of Participants Experiencing a Vaccine-related AE After ProQuad® Dose 2	The percentage of participants experiencing a vaccine-related AEs for up to 28 days after the second ProQuad® injection was determined.	Up to Day 70 (up to 28 days after ProQuad® Dose 2)
Percentage of Participants Experiencing a Solicited Injection-site AE After ProQuad® Dose 2	The solicited injection-site AEs erythema, swelling, and pain were monitored for 4 days after administration of ProQuad® Dose 2.	Up to Day 46 (for 4 days following ProQuad® Dose 2)
Percentage of Participants Experiencing a Unsolicited Injection-site AE After ProQuad® Dose 2	The percentage of participants experiencing a unsolicited injection-site AE(s) were monitored for up to 28 days after the second ProQuad® injection.	Up to Day 70 (up to 28 days after ProQuad® Dose 2)
Percentage of Participants Experiencing a Injection-site Rash of Interest AE After ProQuad® Dose 2	Injection-site rashes of interest, including measles-like, rubella-like, and vesicular, were monitored for up to 28 days after the second ProQuad® injection.	Up to Day 70 (up to 28 days after ProQuad® Dose 2)
Percentage of Participants Experiencing a Systemic AE After ProQuad® Dose 2	Systemic AEs were monitored for up to 28 days after the second ProQuad® injection.	Up to Day 70 (up to 28 days after ProQuad® Dose 2)
Percentage of Participants Experiencing a Vaccine-related Systemic AE After ProQuad® Dose 2	Vaccine-related systemic AEs were monitored for up to 28 days after the second ProQuad® injection.	Up to Day 70 (up to 28 days after ProQuad® Dose 2)
Percentage of Participants Experiencing a Non-injection-site Rash of Interest AE After ProQuad® Dose 2	Non-injection-site rashes of interest, including measles-like, rubella-like, varicella-like, and zoster-like rashes, were monitored for up to 28 days after the second ProQuad® injection.	Up to Day 70 (up to 28 days after ProQuad® Dose 2)
Percentage of Participants Experiencing a Mumps-like Illness After ProQuad® Dose 2	The percentage of participants experiencing a mumps-like illness for up to 28 days after the second ProQuad® injection was determined.	Up to Day 70 (up to 28 days after ProQuad® Dose 2)
Percentage of Participants Experiencing a Serious AE (SAE) After ProQuad® Dose 2	Serious AEs ere defined as any untoward consequence that results in death, is life-threatening, requires hospitalization or prolongs existing hospitalization, is a congenital anomaly/birth defect, or is any other medically important event.	Up to Day 84 (up to 42 days after ProQuad® Dose 2)
Percentage of Participants Experiencing a Vaccine-related SAE After ProQuad® Dose 2	Vaccine-related SAEs were defined as any untoward consequence that results in death, is life-threatening, requires hospitalization or prolongs existing hospitalization, is a congenital anomaly/birth defect, or is any other medically important event.	Up to Day 84 (up to 42 days after ProQuad® Dose 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing a Solicited Injection-site AE After ProQuad® Dose 1	The solicited injection-site AEs erythema, swelling, and pain were monitored for 4 days after administration of ProQuad® Dose 1.	From Day 1 to Day 4 (for 4 days following ProQuad® Dose 1)
Percentage of Participants Experiencing a Unsolicited Injection-site AE After ProQuad® Dose 1	Unsolicited injection-site AEs were monitored for up to 28 days after the first ProQuad® injection.	Up to Day 28 (28 days after ProQuad® Dose 1)
Percentage of Participants With ≥ 1 Rectal Temperature Reading ≥ 38.0° C After ProQuad® Dose 1	The percentage of participants with at least 1 rectal temperature reading ≥ 38.0° C was determined.	Up to Day 28 (28 days after ProQuad® Dose 1)
Percentage of Participants Experiencing a Systemic AE After ProQuad® Dose 1	Systemic AEs were monitored for up to 28 days after the first ProQuad® injection.	Up to Day 28 (28 days after ProQuad® Dose 1)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Anne FIQUET, MD, MCM Vaccines B.V.

Publications and helpful links

General Publications

• Ruger G, Gabutti G, Rumke H, Rombo L, Bernaola E, Diez-Domingo J, Martinon-Torres F, Hogh B, Konstantopoulos A, Fiquet A, Thomas S, Eymin C, Baudin M. Safety of a 2-dose regimen of a combined measles, mumps, rubella and varicella live vaccine manufactured with recombinant human albumin. Pediatr Infect Dis J. 2012 Nov;31(11):1166-72. doi: 10.1097/INF.0b013e318267fd8b. Erratum In: Pediatr Infect Dis J. 2012 Dec;31(12):1319.

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2007
• Primary Completion (Actual): November 24, 2008
• Study Completion (Actual): November 24, 2008

Study Registration Dates

• First Submitted: November 19, 2007
• First Submitted That Met QC Criteria: November 19, 2007
• First Posted (Estimate): November 20, 2007

Study Record Updates

• Last Update Posted (Actual): October 17, 2017
• Last Update Submitted That Met QC Criteria: September 18, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Prevention of: measles, mumps, rubella and varicella
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; DNA Virus Infections; Morbillivirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Togaviridae Infections; Rubivirus Infections; Measles; Herpes Zoster; Chickenpox; Rubella
• Other Study ID Numbers: V221-037; MRV01C (Other Identifier: Sanofi Pasteur MSD Protocol Number); 2007-002438-12 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No