E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV+ teenagers and young adults versus HIV-negative subjects: high-risk population for HPV-related disease. |
Adolescenti e giovani adulti HIV infetti versus HIV-negativi: popolazione ad elevato rischio di patologie HPV correlate. |
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E.1.1.1 | Medical condition in easily understood language |
HIV+ teenagers and young adults versus HIV-negative subjects |
Adolescenti e giovani adulti HIV infetti versus HIV-negativi |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063001 |
E.1.2 | Term | Human papilloma virus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
• To assess the immunogenicity of quadrivalent human papillomavirus vaccine (Gardasil) in male and female HIV-infected adolescents and young adults, by evaluation of type-specific antibody development for HPV types 6, 11, 16 and 18 from seronegative status at baseline (T0) to seropositive status at a month after the completion of HPV vaccine series (T3), compared with the same immunogenicity testings performed in healthy subjects of the same age. |
Valutare l’immunogenicità di un vaccino quadrivalente anti-HPV (Gardasil) in adolescenti e giovani adulti HIV-infetti di entrambi i sessi mediante il dosaggio di anticorpi specifici anti-HPV 6, 11, 16, 18 al baseline (T0) e ad un mese dopo la fine del ciclo vaccinale (T3) a confronto con i risultati ottenuti in una popolazione sana valutata ai medesimi tempi |
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E.2.2 | Secondary objectives of the trial |
Evaluate HPV antibody titers to types 6, 11, 16, 18, one month after each vaccination dose (T1, T2, T3) in HIV-infected adolescents and young adults compared with the same immunological testings in healthy adolscents and young adults.
To assess long-term immunogenicity of quadrivalent human papillomavirus vaccine (Gardasil) in HIV-infected and healthy subjects by evaluation of persistence of HPV antibody titers to types 6, 11, 16 and 18 at month 12 (T4) and 18 (T5) from baseline (T0).
To assess the safety and tolerability of three doses of quadrivalent human papillomavirus vaccine (Gardasil) in HIV-infected and healthy subjects by evaluating the occurrence and severity of local and systemic adverse events during the 7 days after each vaccination dose.
Longitudinal monitoring of HIV-viral load and CD4 count in HIV-infected subjects from baseline (T0), throughout the study. |
Ottenere dati di cinetica anticorpale mediante il dosaggio degli anticorpi specifici anti HPV 6, 11, 16, 18 un mese dopo ciascuna dose di vaccino (T1, T2, T3) nei soggetti HIV-infetti e sani.
Valutare la persistenza anticorpale nei soggetti HIV- infetti e sani dopo 12 (T4) e 18 mesi (T5) dall’inizio del ciclo vaccinale (T0).
Valutare il profilo di sicurezza del vaccino quadrivalente anti-HPV (Gardasil) in adolescenti e giovani adulti HIV- infetti e sani di entrambi i sessi.
Monitorare il profilo viro-immunologico dei soggetti HIV-infetti di entrambi i sessi durante lo studio mediante dosaggio dei linfociti T CD4+ e dell’HIV-RNA al baseline, un mese dopo ciascuna dose di vaccino (T1, T2, T3), a 12 e 18 mesi dal baseline (T4, T5). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For both HIV-infected and healthy subjects:
• Subjects aged 13-27 years
• Females or males
• Written informed consent from parent or guardian if applicable (age <18 years)
For HIV-infected subjects:
• HIV-positive
• Asymptomatic subjects (possible with only generalized lymphadenopathy).
• Lymphocyte CD4+ count > 350 cell/mm3
• For subjects receiving HAART:
- Goog compliance to therapy
- At least two suppressed viral loads HIV-RNA (<37cp/ml) during 6 months prior to enrollment in study. |
Per entrambe le popolazioni in studio (HIV- infetti e soggetti sani):
• Soggetti di età compresa tra 13 e 27 anni.
• Sesso femminile o maschile.
• Consenso informato firmato dal soggetto maggiorenne o dal genitore o legale rappresentante per i soggetti minorenni.
Per i soggetti HIV- infetti:
• Diagnosi certa di infezione da HIV.
• Soggetti asintomatici al momento dell’arruolamento (o anche solo con linfadenopatia persistente generalizzata).
• Conta dei linfociti T CD4+ > 350 cell/mm3.
• Per i soggetti che assumono terapia antiretrovirale:
- buona compliance alla terapia.
- almeno due cariche virali negative (<37cp/ml) in due determinazioni distinte nei 6 mesi. antecedenti all’arruolamento nello studio.
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Per i soggetti di sesso femminile sessualmente attive sia HIV- infette che sane:
• Anamnesi negativa per esame CIN 2/3 con genotipo HPV positivo per 16, 18.
• Anamnesi negativa per malformazioni e/o interventi chirurgici alla cervice uterina.
• In soggetti fertili:
- Test di gravidanza negativo al momento dell’arruolamento. |
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E.4 | Principal exclusion criteria |
For female subjects (both HIV-infected and healthy) :
• Current (within 6 months prior to study entry) abnormal Pap test with confirmed biopsy results of cervical intraepithelial neoplasia CIN 2/3 caused by genotype HPV 16, 18 or cervical cancer within 180 days prior to study entry.
• Pregnancy or breastfeeding
• Total hysterectomy. Participants who have undergone partial hysterectomy and have a cervix are not excluded
For both females and males (HIV-infected and healthy):
• Prior vaccination with quadrivalent HPV vaccine (Gardasil) before study entry.
• History of severe allergic reaction after previous vaccination or hypersensytivity to any vaccine component
• Any serious chronic or progressive disease (other than HIV) according to the judgment of the investigator:
- Acute infection requiring therapy or fever at time of enrollment
- Chronic autoimmune or oncologic disease receiving chemotherapy
- Tuberculosis
- Neurologic disease or history of convulsions
• Concomitant therapies (other than HAART):
- Chronic therapy ( for more than 14 days consecutively) with immunosoppressive or immunomodulating agents or chemotherapy during the 6 months prior to study entry.
- Ongoing anti-tubercular therapy
- Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation prior to study entry
• Severe anemia: hemoglobin less than 8.0 g/dL.
• Acute or chronic impairment of pulmonary, cardiac, hepatic o renal function.
• Use of investigational agents within 4 weeks prior to study enrollment.
• Current drug or alcohol use or dependence
• Documented history of non-adherence to antiretroviral treatment regimen within 12 months prior to study entry. |
• Precedente immunizzazione con vaccino anti-HPV o prevista vaccinazione anti- HPV diversa da Gardasil durante lo studio in oggetto.
• Precedente somministrazione di componenti del vaccino in studio.
• Altre patologie concomitanti:
- Malattia acuta e/o iperpiressia al momento dell’arruolamento.
- Malattie croniche autoimmunitarie o oncologiche in terapia.
- Tubercolosi in fase attiva.
- Malattie neurologiche o anamnesi positiva per convulsioni.
• Altre terapie concomitanti:
- Terapia cronica (definita come terapia per > 14 giorni consecutivi) con immunosoppressori e/o altri farmaci immunomodulanti nei 6 mesi antecedenti la prima dose del vaccino anti- HPV Gardasil.
- Terapia antitubercolare in corso.
- Esecuzione di trasfusioni di sangue e/o derivati del sangue e/o immunoglobuline nei 3 mesi antecedenti la vaccinazione o previsione di eseguirle durante il periodo dello studio.
- Assunzione di trimethoprim/sulpamethoxazole nei 7 giorni antecedenti la prima dose del vaccino anti-HPV o prevista somministrazione durante il periodo di studio.
• Scarsa compliance alla terapia antiretrovirale per il paziente HIV- infetti in terapia.
• Somministrazione di un farmaco o vaccino sperimentale o non-registrato nei 30 giorni antecedenti la prima dose di vaccino anti- HPV (Gardasil) o previsto durante lo studio.
• Ipersensibilità al lattice.
• Anamnesi positiva per reazioni allergiche ad una precedente vaccinazione o storia di ipersensibilità ad un componente di un vaccino.
• Soggetti di sesso femminile che durante il periodo dello studio cercheranno una gravidanza o abbiano intenzione di interrompere le precauzioni contraccettive.
• Gravidanza e /o allattamento.
• Abuso di alcolici o droghe. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Type-specific antibody development for HPV types 6, 11, 16 and 18 from seronegative status at baseline to seropositive status at a month after the completion of HPV vaccine series. |
Sieroconversione per i differenti sierotipi di HPV (6, 11, 16 e 18 ) ad un mese dopo la fine del ciclo vaccinale. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
One month after the completion of HPV vaccine series. |
Un mese dalla fine del ciclo vaccinale. |
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E.5.2 | Secondary end point(s) |
Antibody kinetics and persistance. |
Cinetica e persistenza anticorpale. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At 1 month after each dose and 12 and 18 months from the first dose. |
Ad un mese da ogni dose vaccinale e a 12 e 18 mesi dalla prima dose. |
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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 | 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 | No |
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 | Yes |
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 |
HIV+ vs HIV- |
HIV+ vs HIV- |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
E.8.7 | Trial has a data monitoring committee | No |
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 | 30 |
E.8.9.1 | In the Member State concerned days | 0 |