Evaluation of the Immunogenicity and Safety of GlaxoSmithKline Biologicals' HPV Vaccine in Young Males.

Study Overview
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Brief Summary
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The main aim of this vaccine is to prevent cervical cancer in women. However, it could also be relevant to vaccinate selected groups of males. Therefore, this study is designed to evaluate the safety and immunogenicity of the HPV vaccine in pre-teen and adolescent male subjects aged 10-18 years.

Official Title
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An Observer-blind, Randomized, Controlled Study to Assess the Immunogenicity and Safety of GlaxoSmithKline Biologicals' HPV Vaccine Administered Intramuscularly According to a 0, 1, 6 Month Schedule in Healthy Male Subjects Aged 10-18 Years

Conditions
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Infections, Papillomavirus

Intervention / Treatment
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* Biological: Cervarix vaccine
* Biological: Engerix-B vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: A male between, and including, 10 and 18 years of age at the time of the first vaccination. Written informed consent obtained from the subject prior to enrolment For subjects below the legal age of consent, a written informed consent must be obtained from the subject's parent/guardian. In addition, a written informed assent must be obtained from the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Free of obvious health problems as established by medical history and clinical examination before entering into the study. Exclusion criteria: Previous vaccination against Human Papillomavirus (HPV). Previous vaccination against Hepatitis B, known clinical history of Hepatitis B infection. Cancer or autoimmune disease under treatment.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cervarix Group<br>Healthy male subjects between and including 10 to 18 years of age at the time of the first vaccination, who were administered 3 doses of Cervarix™ (HPV-16/18 L1 VLP AS04) vaccine, intramuscularly into the deltoid region of the non-dominant arm, according to a 0, 1 and 6-month schedule. The subjects were followed up for 7 months after the first dose and an additional telephone contact was foreseen at Month 12. | Biological: Cervarix vaccine<br>* All subjects received an intramuscular injection into the deltoid of the non-dominant arm according to a 0, 1 and 6-month schedule.<br>* Other names: HPV vaccine;|
| Active Comparator: Engerix-B Group<br>Healthy male subjects between and including 10 to 18 years of age at the time of the first vaccination, who were administered 3 doses of Engerix-B™ (HBV) vaccine, intramuscularly into the deltoid region of the non-dominant arm, according to a 0, 1 and 6-month schedule. The subjects were followed up for 7 months after the first dose and an additional telephone contact was foreseen at Month 12. | Biological: Engerix-B vaccine<br>* All subjects received an intramuscular injection into the deltoid of the non-dominant arm according to a 0, 1 and 6-month schedule<br>* Other names: HBV vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 | Seroconversion was defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies [anti-HPV-16 titers greater than or equal to (≥) 8 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL) and anti-HPV-18 titres ≥7 EL.U/mL] in the serum of subjects seronegative before vaccination. | At Month 7 | 
| Antibody Titers Against HPV-16 (Anti-HPV-16) and HPV-18 (Anti-HPV-18) | Titers were presented as geometric mean titers (GMT). | At Month 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 | Seroconversion was defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies (anti-HPV-16 titres ≥ 8 EL.U/mL and anti-HPV-18 titres ≥ 7 EL.U/mL) in the serum of subjects seronegative before vaccination. | At Month 2 | 
| Antibody Titers Against HPV-16 (Anti-HPV-16) and HPV-18 (Anti-HPV-18) | Titers were presented as GMTs. | At Month 2 | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Solicited local symptoms assessed were pain, redness and swelling. Any = any solicited local symptom irrespective of intensity grade; Grade 3 pain = pain that prevented normal activity; Grade 3 redness/swelling = redness/swelling spreading beyond (>) 50 mm. | Within 7 days (Days 0-6) after each dose and across doses, up to 7 months | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Solicited general symptoms assessed were arthralgia, fatigue, fever (defined as axillary temperature ≥37.5 °C), gastrointestinal, headache, myalgia, rash and urticaria. Any = any solicited general symptom irrespective of intensity grade or relationship to vaccination; Grade 3 = symptom that prevented normal activity; Grade 3 fever = temperature > 39.0 °C; Related = symptoms considered by the investigator to have a causal relationship to vaccination. | Within 7 days (Days 0-6) after each dose and across doses, up to 7 months | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) | An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination. | Within 30 days (Day 0-29) after any vaccination, up to 7 months | 
| Number of Subjects With New Onset of Chronic Diseases (NOCDs) and Other Medically Significant Conditions | NOCDs include asthma, Chron's disease, dermatitis atopic. MSCs include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections and injury. | Throughout the active phase of the study (up to Month 7) and the extended safety follow-up (from Month 7 up to Month 12) | 
| Number of Subjects With Serious Adverse Events (SAEs) | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | Throughout the active phase of the study (up to Month 7) and the extended safety follow-up (from Month 7 up to Month 12) | 
| Number of Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters | The occurence of clinically relevant abnormalities was assessed in the following biochemical and haematological parameters: alanine aminotransferase [ALT], basophils [BAS], creatinine [CREA], eosinophils [EOS] and hematocrit [Hem]. Levels of haematological/biochemical parameters assessed in terms of normal, below and above laboratory values were - normal, below, above and missing. | At Month 2 and Month 7, post-vaccination | 
| Number of Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters | The occurence of clinically relevant abnormalities was assessed in the following biochemical and haematological parameters: lymphocytes [LYM], monocytes [MON], neutrophils [NEU], platelets [PLA], red blood cells [RBC] and white blood cells [WBC]. Levels of haematological/biochemical parameters assessed in terms of normal, below and above laboratory values were - normal, below, above and missing. | At Month 2 and at Month 7, post-vaccination |