ClinicalTrials.gg
Sign In
CompletedNCT00432042Updated Mar 19, 2018Results posted

Immunogenicity and Safety Study of Proquad® and Infanrix® Hexa When Administered Concomitantly (V221-035)

A Phase 3 interventional study of ProQuad® and Infanrix® hexa in Varicella, Measles and Mumps, sponsored by Merck Sharp & Dohme LLC. Completed at 50 sites in 2 countries. Open to participants aged 12 Months to 23 Months, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-03-19.

Sponsored by Merck Sharp & Dohme LLC (part of Merck & Co., Inc) · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
955
Allocation
Randomized
Ages
12 Months to 23 Months
Sex
All
01

Study summary

Primary Objective:

  • To demonstrate that ProQuad® can be administered concomitantly with a booster dose of Infanrix® hexa to healthy children 12 to 23 months of age without impairing either the antibody response rates to measles, mumps, rubella, varicella, hepatitis B and Haemophilus influenzae type b; or to the 3 pertussis antibody titres measured at 42 days following vaccination.

Secondary Objectives:

  • To describe the antibody titres and the antibody response rates to measles, mumps, rubella, varicella, diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b as measured at 42 days following vaccination by an Infanrix® hexa primary series schedule and all data are pooled.
  • To evaluate the safety profile of ProQuad® when administered concomitantly with a booster dose of Infanrix® hexa by an Infanrix® hexa primary series schedule and all data are pooled.
02

Conditions studied

  • Varicella
  • Measles
  • Mumps
  • Rubella
  • Diphtheria
  • Tetanus
  • Pertussis
  • Poliomyelitis
  • Hepatitis B
  • Haemophilus Infections

Keywords

  • Mumps and Rubella
  • Haemophilus influenzae type b (Infanrix® hexa)
03

In context

Chickenpox

180 studies on the registry are indexed under Chickenpox; 28 are open to participants now.

This study's enrollment of 955 is above the median of 475 across 149 interventional studies indexed under Chickenpox.

Browse Chickenpox studies →

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,166 studies on the registry; 132 are open to participants now.

Of its 501 completed or terminated interventional studies of FDA-regulated products, 370 (74%) have results posted.

Browse Merck Sharp & Dohme LLC studies →All Merck & Co., Inc studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
12 Months to 23 Months
Sexes eligible
All
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Healthy participants of either gender
  • Aged 12 to 23 months
  • No clinical history of measles, mumps, rubella, varicella and zoster
  • For Italy: Primary vaccination with the combined diphtheria, tetanus, pertussis, , poliomyelitis and Haemophilus influenzae type b vaccine Infanrix® hexa as a 2-dose schedule, with receipt of the second dose ≥ 6 months prior to inclusion
  • For Germany: Primary vaccination with the combined diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b vaccine Infanrix® hexa as a 3-dose schedule, with receipt of the third dose ≥ 6 months prior to inclusion
  • Consent form signed by parent(s) according to local regulations or by the legal representative properly informed about the study
  • Parent(s)/legal representative able to understand the protocol requirements and to fill in the Diary Card.

Exclusion criteria

Exclusion Criteria:

  • Prior receipt of measles, mumps, rubella and/or varicella vaccine either alone or in any combination
  • Any recent (\<= 30 days) exposure to measles, mumps, rubella, varicella and/or zoster
  • Receipt of any other diphtheria, tetanus, pertussis, , poliomyelitis and/or Haemophilus influenzae type b containing vaccine (either alone or in any combination) than Infanrix® hexa
  • Any recent (\<= 3 days) history of febrile illness
  • Any severe chronic disease
  • Active untreated tuberculosis
  • Known personal history of encephalopathy, seizure disorder or progressive, evolving or unstable neurological condition
  • Any known blood dyscrasia, leukemia, lymphomas of any type, or other malignant neoplasms affecting the haematopoietic or lymphatic systems
  • Any severe thrombocytopenia or any other coagulation disorder that would contraindicate intramuscular injection
  • Prior known sensitivity/allergy to any component of the vaccines including neomycin, sorbitol or gelatin
  • Any immune impairment or humoral/cellular deficiency, neoplastic disease or depressed immunity
  • Any recent (\<= 2 days) tuberculin test or scheduled tuberculin test through Visit 2
  • Any previous (\<= 150 days) receipt of immune serum globulin or any blood-derived products or scheduled to be administered through Visit 2
  • Any recent (\<= 30 days) receipt of an inactivated or a live non-study vaccine or scheduled non-study vaccination through Visit 2
  • Any medical condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives
  • Any recent (≤30 days) participation or scheduled participation in any other clinical trial through Visit 2
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

05

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
955 participants (actual)

Study arms

  • Experimental
    ProQuad® + Infanrix® hexa

    Pediatric (12 to 23 months of age) participants received ProQuad® and Infanrix® hexa (booster dose) concomitantly on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).

    Biological: ProQuad® · Biological: Infanrix® hexa

  • Active comparator
    ProQuad®

    Pediatric (12 to 23 months of age) participants received ProQuad® on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).

    Biological: ProQuad®

  • Active comparator
    Infanrix® hexa

    Pediatric (12 to 23 months of age) participants received Infanrix® hexa (booster dose) on Visit 1 (Day 0). Blood samples were taken on Visit 1 and Visit 2 (Day 42).

    Biological: Infanrix® hexa

Interventions

  • BiologicalProQuad®

    Participants received a 0.5 mL subcutaneous injection of ProQuad® containing the following live attenuated virus strains: measles virus Enders' Edmonston strain (≥3.00 log10 50% cell culture infectious dose \[CCID\]50), mumps virus Jeryl Lynn™ (Level B) strain (≥4.30 log10 CCID50), rubella virus Wistar RA 27/3 strain (≥3.00 log10 CCID50), and varicella virus Oka/Merck strain (≥3.99 log10 plaque-forming units \[PFU\]).

  • BiologicalInfanrix® hexa

    Participants received a 0.5 mL intramuscular injection of Infanrix® hexa containing the following: diphtheria toxoid (≥30 IU), tetanus toxoid (≥40 IU), 3-component acellular pertussis (pertussis taxoid, filamentous haemagglutinin, and pertactin) (25 ug), Hepatitis B surface antigen recombinant (S protein) (10 ug), inactivated poliovirus types 1-3 (type 1: 40 D-antigen units; type 2: 8 D-antigen units; type 3: 32 D-antigen units), and Haemophilus influenzae type B (Hib) polysaccharide conjugate to tetanus toxoid (20-40 ug).

06

What researchers measure

Primary outcomes

  1. Percentage of Participants Meeting Antibody Response Rate Criteria to Measles, Mumps, Rubella, and Varicella

    The percentage of participants with seronegative baseline values who met antibody response criteria in Arm 1: ProQuad® + Infanrix® hexa and Arm 2: ProQuad® was determined. Post-vaccination antibody response and baseline seronegativity criteria were as follows: measles antibody titre ≥255 mIU/mL in participants with baseline titre \<255 mIU/mL; mumps antibody titre ≥10 ELISA Ab units/mL in participants with baseline titre \<10 ELISA Ab units mL; rubella antibody titre ≥10 IU/mL in participants with baseline titre \<10 IU/mL; varicella antibody titre ≥5 gpELISA units/mL in participants with baseline titre \<1.25 gpELISA units/mL. Measles, mumps and rubella antibody levels were determined using enzyme-linked immunosorbent assay (ELISA) and varicella antibody levels were determined with glycoprotein-based ELISA (gpELISA).

    Time frame: Day 42

  2. Percentage of Participants Meeting Post-vaccination Antibody Response Rates to Hepatitis B and Haemophilus Influenzae Type B

    The percentage of participants with seronegative baseline values who met antibody response criteria in Arm 1: ProQuad® + Infanrix® hexa and Arm 3: Infanrix® hexa was determined. Post-vaccination antibody response and baseline seronegativity criteria were as follows: Hepatitis B antibody titre ≥10 IU/mL and Haemophilus Influenzae Type b antibody titre ≥1 ug/mL. Hepatitis B antibody levels were determined using anti-HBs ORTHO ECi Immunodiagnostic Assay. Haemophilus Influenzae Type b antibody (anti-polyribosylribitol phosphate \[PRP\]) levels were determined with radioimmunoassay (RIA) or with enzyme immunoassay (EIA).

    Time frame: Day 42

  3. Post-vaccination Geometric Mean Titres (GMT) to Pertussis

    The GMT to pertussis were compared in Arm1: ProQuad® + Infanrix® hexa and Arm 3: Infanrix® hexa. Anti-pertussis toxin (anti-PT), anti-filamentous hemagglutinin (anti-FHA), and anti-pertactin (anti-PRN) were determined using ELISA on solid phase based on sandwich principle.

    Time frame: Day 42

07

Results

Posted Mar 19, 2018

Participant flow

A total of 963 participants were screened at study centers in Italy and Germany.

Participant flow — Overall Study
MilestoneArm 1: ProQuad® + Infanrix® HexaArm 2: ProQuad®Arm 3: Infanrix® Hexa
Started479235241
Vaccinated477235240
Completed472234239
Not completed712
Withdrew: Protocol violation200
Withdrew: Withdrawal by subject002
Withdrew: Lost to follow-up510

Outcome measures

PrimaryPercentage of Participants Meeting Antibody Response Rate Criteria to Measles, Mumps, Rubella, and Varicella

The percentage of participants with seronegative baseline values who met antibody response criteria in Arm 1: ProQuad® + Infanrix® hexa and Arm 2: ProQuad® was determined. Post-vaccination antibody response and baseline seronegativity criteria were as follows: measles antibody titre ≥255 mIU/mL in participants with baseline titre \<255 mIU/mL; mumps antibody titre ≥10 ELISA Ab units/mL in participants with baseline titre \<10 ELISA Ab units mL; rubella antibody titre ≥10 IU/mL in participants with baseline titre \<10 IU/mL; varicella antibody titre ≥5 gpELISA units/mL in participants with baseline titre \<1.25 gpELISA units/mL. Measles, mumps and rubella antibody levels were determined using enzyme-linked immunosorbent assay (ELISA) and varicella antibody levels were determined with glycoprotein-based ELISA (gpELISA).

Time frame:
Day 42
Reported as:
Number · Percentage of Participants
Percentage of Participants Meeting Antibody Response Rate Criteria to Measles, Mumps, Rubella, and Varicella
Percentage of ParticipantsArm 1: ProQuad® + Infanrix® HexaArm 2: ProQuad®
Measles97.4 (95.4 to 98.7)96.3 (92.8 to 98.4)
Mumps96.7 (94.6 to 98.2)98.6 (95.9 to 99.7)
Rubella97.9 (96.1 to 99.0)99.1 (96.7 to 99.9)
Varicella97.7 (95.7 to 99.0)95.1 (91.2 to 97.6)
Statistical analysis
  • Arm 1: ProQuad® + Infanrix® Hexa vs Arm 2: ProQuad® · Mean difference (final values): 1.14 · 95% CI -1.62 to 4.82Non-inferiority was declared when the lower bound of the two-sided 95% CI of the difference is \> -10%.
  • Arm 1: ProQuad® + Infanrix® Hexa vs Arm 2: ProQuad® · Mean difference (final values): -1.83 · 95% CI -4.21 to 1.10Non-inferiority was declared when the lower bound of the two-sided 95% CI of the difference is \> -10%.
  • Arm 1: ProQuad® + Infanrix® Hexa vs Arm 2: ProQuad® · Mean difference (final values): -1.20 · 95% CI -3.19 to 1.35Non-inferiority was declared when the lower bound of the two-sided 95% CI of the difference is \> -10%.
  • Arm 1: ProQuad® + Infanrix® Hexa vs Arm 2: ProQuad® · Mean difference (final values): 2.53 · 95% CI -0.41 to 6.58Non-inferiority was declared when the lower bound of the two-sided 95% CI of the difference is \> -10%.
PrimaryPercentage of Participants Meeting Post-vaccination Antibody Response Rates to Hepatitis B and Haemophilus Influenzae Type B

The percentage of participants with seronegative baseline values who met antibody response criteria in Arm 1: ProQuad® + Infanrix® hexa and Arm 3: Infanrix® hexa was determined. Post-vaccination antibody response and baseline seronegativity criteria were as follows: Hepatitis B antibody titre ≥10 IU/mL and Haemophilus Influenzae Type b antibody titre ≥1 ug/mL. Hepatitis B antibody levels were determined using anti-HBs ORTHO ECi Immunodiagnostic Assay. Haemophilus Influenzae Type b antibody (anti-polyribosylribitol phosphate \[PRP\]) levels were determined with radioimmunoassay (RIA) or with enzyme immunoassay (EIA).

Time frame:
Day 42
Reported as:
Number · Percentage of participants
Percentage of Participants Meeting Post-vaccination Antibody Response Rates to Hepatitis B and Haemophilus Influenzae Type B
Percentage of participantsArm 1: ProQuad® + Infanrix® HexaArm 3: Infanrix® Hexa
Hepatitis B99.5 (98.3 to 99.9)98.1 (95.3 to 99.5)
Haemophilus Influenzae Type B98.2 (96.3 to 99.3)95.3 (91.5 to 97.7)
Statistical analysis
  • Arm 1: ProQuad® + Infanrix® Hexa vs Arm 3: Infanrix® Hexa · Mean difference (final values): 1.36 · 95% CI -0.29 to 4.24Non-inferiority was declared when the lower bound of the two-sided 95% CI of the difference is \> -5%.
  • Arm 1: ProQuad® + Infanrix® Hexa vs Arm 3: Infanrix® Hexa · Mean difference (final values): 2.97 · 95% CI -0.17 to 6.89Non-inferiority was declared when the lower bound of the two-sided 95% CI of the difference is \> -5%.
PrimaryPost-vaccination Geometric Mean Titres (GMT) to Pertussis

The GMT to pertussis were compared in Arm1: ProQuad® + Infanrix® hexa and Arm 3: Infanrix® hexa. Anti-pertussis toxin (anti-PT), anti-filamentous hemagglutinin (anti-FHA), and anti-pertactin (anti-PRN) were determined using ELISA on solid phase based on sandwich principle.

Time frame:
Day 42
Reported as:
Number · GMT (IU/mL)
Post-vaccination Geometric Mean Titres (GMT) to Pertussis
GMT (IU/mL)Arm 1: ProQuad® + Infanrix® HexaArm 3: Infanrix® Hexa
Anti-PT GMT132.6 (123.8 to 142.0)139.1 (126.7 to 152.8)
Anti-FHA GMT210.9 (195.7 to 227.2)189.9 (170.2 to 211.8)
Anti-PRN GMT310.0 (282.2 to 340.7)259.7 (226.3 to 298.1)
Statistical analysis
  • Arm 1: ProQuad® + Infanrix® Hexa · Gmt ratio: 0.97 · 95% CI 0.88 to 1.08Non-inferiority was declared when the lower bound of the two-sided 95% CI of the difference is \> -5%.
  • Arm 1: ProQuad® + Infanrix® Hexa · Gmt ratio: 1.09 · 95% CI 0.98 to 1.23Non-inferiority was declared when the lower bound of the two-sided 95% CI of the difference is \> -5%.
  • Arm 1: ProQuad® + Infanrix® Hexa vs Arm 3: Infanrix® Hexa · Gmt ratio: 1.18 · 95% CI 1.03 to 1.36Non-inferiority was declared when the lower bound of the two-sided 95% CI of the difference is \> -5%.

Adverse events

Collected over Up to Day 42. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arm 1: ProQuad® + Infanrix® Hexa—7/474 (1.5%)409/474 (86.3%)
Arm 2: ProQuad®—6/234 (2.6%)134/234 (57.3%)
Infanrix® Hexa—4/239 (1.7%)184/239 (77%)
Most frequent serious events
Showing 10 of 12
Most frequent serious events
EventArm 1: ProQuad® + Infanrix® HexaArm 2: ProQuad®Infanrix® Hexa
BronchitisInfections and infestations0/4743/2341/239
BronchopneumoniaInfections and infestations1/4741/2340/239
Conjunctivitis bacterialInfections and infestations0/4741/2340/239
Gastroenteritis rotavirusInfections and infestations1/4741/2341/239
Upper respiratory tract infectionInfections and infestations0/4741/2340/239
Febrile convulsionNervous system disorders2/4740/2340/239
InfluenzaInfections and infestations0/4740/2341/239
Electric shockInjury, poisoning and procedural complications0/4740/2341/239
GastroenteritisInfections and infestations1/4740/2340/239
Otitis mediaInfections and infestations1/4740/2340/239
Most frequent other events
Showing 10 of 11
Most frequent other events
EventArm 1: ProQuad® + Infanrix® HexaArm 2: ProQuad®Infanrix® Hexa
Injection site erythemaGeneral disorders274/47431/234126/239
Injection site swellingGeneral disorders203/4747/23493/239
Injection site painGeneral disorders198/47433/23484/239
PyrexiaGeneral disorders184/47480/23468/239
NasopharyngitisInfections and infestations48/47414/23418/239
RhinitisInfections and infestations27/47420/2349/239
Rash morbilliformSkin and subcutaneous tissue disorders33/47416/2345/239
CoughRespiratory, thoracic and mediastinal disorders31/47413/23411/239
DiarrhoeaGastrointestinal disorders22/47414/23414/239
VomitingGastrointestinal disorders14/4742/23414/239

Baseline characteristics

Age, Continuous
Age, Continuous(Months)Arm 1: ProQuad® + Infanrix® HexaArm 2: ProQuad®Arm 3: Infanrix® HexaTotal
Mean13.6 ± 1.913.4 ± 1.513.5 ± 1.713.5 ± 1.7
Sex: Female, Male
Sex: Female, Male(Participants)Arm 1: ProQuad® + Infanrix® HexaArm 2: ProQuad®Arm 3: Infanrix® HexaTotal
Female222112114448
Male257123127507
08

Study locations

50 sites
  • Alsfeld, Germany
  • Bad Saulgau, Germany
  • Bad Sobernheim, Germany
  • Bad Säckingen, Germany
  • Berlin, Germany
  • Bielefeld, Germany
  • Birkenfeld, Germany
  • Bramsche, Germany
  • Bretten, Germany
  • Brunsbüttel, Germany
  • Datteln, Germany
  • Detmold, Germany
  • Espelkamp, Germany
  • Ettenheim, Germany
  • Friedrichshafen, Germany
  • Gerolstein, Germany
  • Gifhorn, Germany
  • Gütersloh, Germany
  • Hamburg, Germany
  • Heilbronn, Germany
  • Herbolzheim, Germany
  • Karlsruhe, Germany
  • Kehl, Germany
  • Koblenz, Germany
  • Lauffen, Germany
  • Mannheim, Germany
  • Marbach, Germany
  • Mönchengladbach, Germany
  • München, Germany
  • Neustadt A.d. Aisch, Germany
  • Nidderau, Germany
  • Oberhausen, Germany
  • Oberkirch, Germany
  • Offenburg, Germany
  • Pegnitz, Germany
  • Rodorf, Germany
  • Schwieberdingen, Germany
  • Schwäbisch Hall, Germany
  • Traunreut, Germany
  • Veitshöchheim, Germany
  • Wanzleben, Germany
  • Welzheim, Germany
  • Wildeshausen, Germany
  • Zwiesel, Germany
  • Chiavari, Italy
  • Ferrara, Italy
  • Latisana, Italy
  • Ragusa, Italy
  • Sassari, Italy
  • Taranto, Italy
09

References and documents

Publications

  • Deichmann KA, Ferrera G, Tran C, Thomas S, Eymin C, Baudin M. Immunogenicity and safety of a combined measles, mumps, rubella and varicella live vaccine (ProQuad (R)) administered concomitantly with a booster dose of a hexavalent vaccine in 12-23-month-old infants. Vaccine. 2015 May 11;33(20):2379-86. doi: 10.1016/j.vaccine.2015.02.070. Epub 2015 Mar 9. PubMed 25765966 ↗

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 19, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00432042
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Feb 6, 2007
Start date
Jan 12, 2007
Primary completion
Mar 27, 2008
Completion
Mar 27, 2008
Results posted
Mar 19, 2018
Last update
Mar 19, 2018

Study contacts

Anne Fiquet, MD
study director · SPMSD

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Feb 2018. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drugs tested here: Measles, mumps, rubella, varicella vaccine · Diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine

Other studies in this condition

Chickenpox →

Other studies from this sponsor

Merck Sharp & Dohme LLC →

Start the discussion