| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Active immunization for the prevention of measles, mumps, rubella, and varicella |
|
| E.1.1.1 | Medical condition in easily understood language |
| Active immunization for the prevention of measles, mumps, rubella, and varicella |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10047461 |
| E.1.2 | Term | Viral infection |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
1. To demonstrate that MMRV vaccine (AMP) induces measles, mumps, rubella, and VZV antibody responses 6 weeks Postdose 1 that are non-inferior to those induced by ProQuadTM (2006 Process).
2. To demonstrate that MMRV vaccine (AMP) induces acceptable measles, mumps, rubella, and VZV antibody responses 6 weeks Postdose 1.
3. To demonstrate that the rate of fever following the first vaccination with MMRV vaccine (AMP) is non-inferior to that following the first vaccination of ProQuad TM (2006 process).
|
|
| E.2.2 | Secondary objectives of the trial |
| 1. To assess the overall safety and tolerability of MMRV vaccine (AMP) when administered to children 12 to 23 months of age. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Merck will conduct Future Biomedical Research on DNA (blood) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described
elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such nformation to develop safer, more effective drugs, and/or to
ensure that subjects receive the correct dose of the correct drug at the
correct time. |
|
| E.3 | Principal inclusion criteria |
a. In good health, based on medical history (physical examination is not required).
b. Twelve (12) to 23 months of age upon receipt of the first study vaccination (subject is able to enroll from the day of his/her first birthday up to 1 day prior to his/her second birthday).
c. A negative clinical history for measles, mumps, rubella, varicella, and zoster.
d. Subject’s legal representative understands the study procedures, alternative treatments available, and risks involved with the study, and voluntarily agrees to participate by giving written informed consent.
e. Subject’s legal representative is able to read, understand, and complete study questionnaires (i.e., VRC).
f. Subject is able to complete all scheduled visits and comply with the study procedures.
g. The subjects’ parent/legal guardian may also provide written informed consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
|
|
| E.4 | Principal exclusion criteria |
If a subject meets any of the exclusion criteria marked with an asterisk (*), the Day 1 visit may be rescheduled for a time when these criteria are no longer met.
a. Received any measles, mumps, rubella, or varicella vaccine, either alone or in any combination at any time prior to the study, or is anticipated to receive any of these vaccines outside of study protocol, either alone or in any combination, during the study.
b. *Vaccinated with a licensed, non-live vaccine (e.g., Inactivated Poliovirus [IPV], Diphtheria, Tetanus, and Acellular Pertussis [DTaP], Haemophilus influenzae type b [Hib]) 14 days or less prior to any dose of the study vaccines or expected to be vaccinated with a licensed, non-live vaccine during the 42-day safety follow-up period after each vaccination in this study.
c. *Vaccinated with any licensed live vaccine within 30 days prior to any dose of the study vaccines or expected to be vaccinated with a licensed live vaccine other than the study vaccines during the 42-day safety follow-up period after each vaccination during in this study.
d. Received immune globulin, a blood transfusion or blood-derived products (does not include autologous blood/blood products) within 5 months (150 days) prior to any dose of the study vaccines or plans to receive these products while enrolled in this study.
e. The subject had an exposure to measles, mumps, rubella, varicella, or zoster within 4 weeks prior to the study vaccination involving: Continuous household contact, or Playmate contact (generally >1 hour of play indoors), or Hospital contact (in the same 2- to 4- bed room or in adjacent beds in a large ward or prolonged contact with an infectious staff member or patient), or In the case of varicella, contact with a newborn whose mother had onset of chickenpox 5 days or less before delivery or within 48 hours after delivery.
f. Any congenital or acquired immune deficiency, neoplastic disease, or depressed immunity, including that resulting from steroid use (See Exclusion Criterion "g") or other immunosuppressive therapy.
g. Subject has received 1) systemic immunomodulatory steroids [greater than the equivalent of 2 mg/kg total daily dose of prednisone] within 3 months prior to entering the study, or 2) any dose of systemic immunomodulatory steroids within 7 days prior to entering study, or 3) is expected to require systemic immunomodulatory steroids through the course of the study.
h. A history of allergy or anaphylactiod reaction to gelatin, sorbitol, neomycin, egg proteins (eggs or egg products), chicken proteins, or any component of the study vaccines.
i. Subject has received salicylates (e.g., aspirin or any aspirin-containing products) within 14 days prior to vaccination.
j. A diagnosis of an active neurological disorder. Enrollment may be considered when the disease process has been stabilized.
k. History of seizure disorder, including single febrile seizure.
l. Diagnosis of active untreated tuberculosis.
m. *A recent (<72 hours) febrile illness (≥102.0°F [≥38.9°C] oral equivalent) prior to the study vaccination.
n. History of thrombocytopenia.
o. Subject was born to an HIV-infected mother.
p. Subject’s legal representative is unlikely to adhere to study procedures, keep appointments, or is planning to relocate during the study.
q. Any other underlying medical condition that, in the opinion of the investigator, may interfere with the evaluation of study objectives.
r. Currently participating in or scheduled to participate in any clinical trial other than a surveillance study at any time prior to completion of clinical and serological follow-up in this study.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The first primary endpoints for the measles, mumps, rubella, and VZV are the respective antibody response rates to each antigen. The response rate for measles is defined as the percent of subjects with measles antibody titer ≥255 mIU/mL 6 weeks Postdose 1 among subjects who are seronegative to measles at baseline (titer <255 mIU/mL). The response rate for mumps is defined as the percent of subjects with mumps antibody titer ≥10 mumps antibody (Ab) units/mL 6 weeks Postdose 1 among subjects who are seronegative to mumps at baseline (titer <10 mumps Ab units/ml). The response rate for rubella is defined as the percent of subjects with rubella antibody titer ≥10 IU/mL 6 weeks Postdose 1 among subjects who are seronegative to rubella at baseline (titer <10 IU/mL). The response rate for VZV is defined as the percent of subjects with VZV antibody titer ≥5 glycoprotein enzyme-linked immunosorbent assay (gpELISA) units/mL 6 weeks Postdose 1 among subjects with baseline VZV antibody titer <1.25 gpELISA units/mL.
The second primary immunogenicity endpoints are the antibody GMTs for each antigen [measles, mumps, rubella, and VZV.
The primary safety endpoint will be rate of fever (temperature 102.2 F [39.0 C] oral equivalent) Days 1 to 5 Postdose 1.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 weeks post dose 1
Days 1 to 5 Postdose 1.
|
|
| E.5.2 | Secondary end point(s) |
A summary of safety for each vaccination group will be provided for:
-Solicited injection-site reactions (redness, swelling, pain/tenderness) of any intensity or size from Days 1 through 5 following each vaccination
-Unsolicited injection-site adverse experiences from Day 1 through Day 42 following each vaccination
-Maximum reported temperature ≥102.2°F (≥39.0°C) oral equivalent from Day 6 through Day 13, Day 1 through Day 15, and Day 1 through Day 42 following each vaccination
-Measles-like, rubella-like, varicella-like, and zoster-like rashes, and mumps-like symptoms occurring from Day 1 through Day 42 following each vaccination
-Systemic adverse experiences from Day 1 through Day 42 following each vaccination
-Serious adverse experiences from enrollment into the study through Day 180 after the second dose of either vaccine.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Day 1 through Day 42 following each vaccination and from enrollment through Day 180 following second dose of either vaccine |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Same vaccine made with an alternative manufacturing process |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
Will this trial be conducted at a single site globally?
| No |
| E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.2 | In all countries concerned by the trial months | 20 |
Print
