E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of Human Papillomavirus Infection |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063001 |
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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 a first dose of REPEVAX™ (diphtheria, tetanus, pertussis [acellular, component] and poliomyelitis [inactivated] vaccine, Sanofi Pastuer, Swiftwater, PA U.S.A.) can be administered concomitantly with the first dose of GARDASIL™† without impairing the antibody response to HPV types 6, 11, 16, and 18, compared to the administration of GARDASIL™ alone.
2. To demonstrate that the first dose of GARDASIL™ can be administered concomitantly with a first dose of REPEVAX™ without impairing the antibody response to diphtheria, tetanus, pertussis and poliomyelitis, compared to the administration of REPEVAX™ alone.
3. To demonstrate that concomitant administration of the first dose of GARDASIL™ with REPEVAX™ will be generally well tolerated compared to when the first dose of GARDASIL™ is given separately from REPEVAX™. |
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E.2.2 | Secondary objectives of the trial |
To demonstrate that GARDASIL™ made in the final manufacturing facility (FMF) induces similar (noninferior) antibody responses to HPV 6, 11, 16 and 18 compared to GARDASIL™ made in the current manufacturing facility (CMF). |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
a. Healthy adolescent boys and girls age 11 to 17 years.
b. Must agree to provide study personnel with a primary telephone number as well as an alternate telephone number for follow-up purposes.
c. Must agree to refrain from sexual activity throughout the course of the study (including vaginal and anal penetration and any genital contact).
d. Subject must have been previously immunized against diphtheria, tetanus, and pertussis (not in the last 5 years). |
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E.4 | Principal exclusion criteria |
a. Individuals concurrently enrolled in clinical studies of investigational agents.
b. History of known prior vaccination with an HPV vaccine.
c. Receipt of inactivated vaccines within 14 days prior to enrollment or receipt of live virus vaccines within 21 days prior to enrollment.
d. Has had coitarche or plans to become sexually active through the course of the study.
e. Temperature ≥100°F or ≥37.8°C (oral) within 24 hours prior to the first injection
f. Pregnant now (as determined by a urine pregnancy test sensitive to 25 IU HCG).
g. Individuals allergic to any of the vaccine components of GARDASIL™ or REPEVAX™ or residues carried over from manufacture (such as formaldehyde, streptomycin, neomycin, and polymoxin B). Individuals who have experienced anaphylactic or other allergic reactions to a previous dose of tetanus or diptheria or a component pertussis combination vaccine. Individuals allergic to aluminum, yeast, phenoxyethanol, or BENZONASE™ (nuclease, Nycomed [used to remove residual nucleic acids from this and other vaccines]).
i. Individuals who have received any immune globulin preparation (including RhoGAM™ [Ortho-Clinical Diagnostics]) or blood-derived products within the 6 months prior to the first injection, or plan to receive any through the completion of the study.
j. Individuals with a history of splenectomy, known immune disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis), or receiving immunosuppressives (e.g., substances or treatments known to diminish immune response such as radiation therapy, administration of antimetabolites, antilymphocytic sera, systemic corticosteroids). Individuals who have received periodic treatments with immunosuppressives, defined as at least 3 courses of systemic corticosteroids each lasting at least 1 week in duration for the year prior to enrollment, will be excluded. Subjects using topical, inhaled or nasal steroids will be eligible for vaccination.
k. Individuals with known hemophilia, thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections.
l. Any condition which in the opinion of the investigator might interfere with the evaluation of the study objectives.
m. Individuals who are immunocompromised or have been diagnosed as having HIV infection.
n. History of recent (within 1 year from the date of enrollment) or ongoing alcohol or other drug abuse. Alcohol abusers are defined as those who drink despite recurrent social, interpersonal, and legal problems as a result of alcohol use.
o. Inability to give consent/assent. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary immunogenicity endpoints for evaluating antibody response to GARDASIL™ are geometric mean titers (GMTs) to HPV 6, 11, 16, and 18 at Week 4 Postdose 3 and the percentages of subjects who seroconvert for each HPV type (6, 11, 16, and 18) by Week 4 Postdose 3. (Seroconversion is defined as changing serostatus from seronegative at baseline to seropositive by Week 4 Postdose 3, where any subject with a cLIA titer at or above the serostatus cutoff for a given HPV type is considered seropositive for that type. Previously, the anti-HPV serum cLIA cutoffs for determining serostatus were 20, 16, 20, and 24 mMU/mL for HPV types 6, 11, 16, and 18, respectively. Due to a change in the cLIA assay, these serostatus cutoffs will be updated at a later time.) The primary immunogenicity endpoints for evaluating antibody response to the diphtheria and tetanus components of REPEVAX™ are the proportions of subjects who achieve titers of at least 0.1IU/mL one month postvaccination of REPEVAX™. The primary immunogenicity endpoints for evaluating antibody response to the polio component of REPEVAX™ are the proportions of subjects who achieve detectable serum neutralizing antibodies at a ≥1:8 dilution one month postvaccination of REPEVAX™. The primary immunogenicity endpoints for pertussis are the GMTs to anti-PT, anti-FHA, anti-PRN and anti-FIM one month postvaccination of REPEVAX™. The primary endpoints for evaluation of GARDASIL™ and their corresponding noninferiority margins have been chosen based on interactions with regulatory agencies (including U.S. FDA) on previous studies. The primary endpoints for evaluation of REPEVAX™ and their corresponding noninferiority margins have been chosen to be consistent with the pivotal licensure studies for that vaccine |
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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 | No |
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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogencity, concomitant use |
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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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |