qanastek/EMEA-V3 huggingface dataset:
As with all injectable vaccines, appropriate medical treatment should always be readily available in case of rare anaphylactic reactions following the administration of the vaccine.
Bħat- tilqim kollu li jingħata b’ injezzjoni, kura medika xierqa għandha tkun dejjem disponibbli immedjatament f' każ ta ’ reazzjonijiet anafilattiċi rari wara l- għoti tal- vaċċin.
Syncope (fainting) may follow any vaccination, especially in adolescents and young adults.
Jista ’ jkun hemm sinkope (sturdament) wara kull vaċċinazzjoni fl- adoloxxenti u ż- żgħażagħ.
Syncope, sometimes associated with falling, has occurred after vaccination with Gardasil (See section 4.8).
Is- sinkope, li xi kultant kienet assoċjata ma ’ waqa ’, ġrat wara li ngħatat il- vaċċinazzjoni b’ Gardasil (ara sezzjoni 4. 8).
Therefore, vaccinees should be carefully observed for approximately 15 minutes after administration of Gardasil.
Għalhekk, il- persuni vaċinati għandhom jiġu osservati għal madwar 15- il minuta wara l- għoti ta ’ Gardasil.
As with any vaccine, vaccination with Gardasil may not result in protection in all vaccine recipients.
Bħal kull vaċċin, it- tilqima b’ Gardasil tista ’ ma tirriżultax fi protezzjoni għar- reċipjenti kollha tal - vaċċin.
Gardasil will only protect against diseases that are caused by HPV types 6, 11, 16 and 18 and to a limited extent against diseases caused by certain related HPV types (See section 5.1).
Gardasil ser jipproteġi biss kontra l- mard ikkawżat mit- tipi 6, 11, 16 u 18 tal- HPV u sa ċertu punt, kontra l- mard ikkawżat minn ċerti tipi ta ’ HPV relatati (ara sezzjoni 5. 1).
Therefore, appropriate precautions against sexually transmitted diseases should continue to be used.
Għaldaqstant, għandhom ikomplu jittieħdu prekawzjonijiet xierqa kontra mard trasmess sesswalment.
Gardasil has not been shown to have a therapeutic effect.
Ma ntweriex li Gardasil għandu effett terapewtiku.
The vaccine is therefore not indicated for treatment of cervical cancer, high-grade cervical, vulvar and vaginal dysplastic lesions or genital warts.
Għalhekk, il- vaċċin mhuwiex indikat għall- kura ta ’ kanċer ċervikali, feriti displastiċi ċervikali, tal- vulva u vaġinali ta 'grad għoli jew felul ġenitali.
It is also not intended to prevent progression of other established HPV-related lesions.
Gardasil, ukoll, mhuwiex maħsub biex jevita l- progress ta ’ feriti oħra stabbiliti marbuta mal- HPV.
Vaccination is not a substitute for routine cervical screening.
It- tilqima ma tieħux post screening ċervikali ta ’ rutina.
Since no vaccine is 100% effective and Gardasil will not provide protection against every HPV type, or against existing HPV infections, routine cervical screening remains critically important and should follow local recommendations.
Peress li l- ebda vaċċin mhu effettiv 100% u Gardasil mhux se jipprovdi protezzjoni kontra kull tip ta ’ HPV jew kontra infezzjonijiet HPV eżistenti, screening ċervikali ta ’ rutina jibqa ’ ta ’ importanza kritika u għandu jsegwi r - rakkomandazzjonijiet lokali.
There are no data on the use of Gardasil in subjects with impaired immune responsiveness.
M’ hemm l- ebda informazzjoni dwar l- użu ta ’ Gardasil f’ pazjenti bi ħsara fir- rispons tas- sistema immuni.
Individuals with impaired immune responsiveness, whether due to the use of potent immunosuppressive therapy, a genetic defect, Human Immunodeficiency Virus (HIV) infection, or other causes, may not respond to the vaccine.
Individwi bi ħsara fir- rispons tas- sistema immuni, kemm jekk dan ikun minħabba terapija immunosuppressiva qawwija, difett ġenetiku, infezzjoni tal- Virus ta 'l- Immunodefiċjenza Umana (HIV) jew kawżi oħra, jistgħu ma jirrispondux għal vaċċin.
This vaccine should be given with caution to individuals with thrombocytopaenia or any coagulation disorder because bleeding may occur following an intramuscular administration in these individuals.
Il- vaċċin għandu jingħata b’ kawtela lil individwi bi tromboċitopenja jew kwalunkwe mard tal - koagulazzjoni minħabba li ħruġ tad- demm jista 'jseħħ wara l- għoti ġol- muskoli f' dawn l- individwi.
The duration of protection is currently unknown.
3 It- tul tal- protezzjoni għadu mhux magħruf fil- preżent.
Sustained protective efficacy has been observed for 3 4.5 years after completion of the 3-dose series.
Effikaċja protettiva sostnuta kienet osservata għal 4. 5 snin wara li ntemmet serje ta ’ 3 dożi.
Longer term follow-up studies are ongoing (see section 5.1).
Studji fit- tul dwar il- follow- up għadhom għaddejjin (ara sezzjoni 5. 1).
There are no safety, immunogenicity or efficacy data to support interchangeability of Gardasil with other HPV vaccines.
Ma hemm ebda tagħrif dwar is- sigurtà, l- immunoġeniċità jew l- effikaċja li jappoġġja l- interkambjalità ta ’ Gardasil ma ’ tilqim HPV ieħor.
In all clinical trials, individuals who had received immunoglobulin or blood-derived products during the 6 months prior to the first vaccine dose were excluded.
Fil- provi kliniċi kolha, l- individwi li kienu rċivew immunoglobulin jew prodotti li ġejjin mid- demm matul is- 6 xhur ta ’ qabel l- ewwel doża tal- vaċċin kienu esklużi.
Use with other vaccines
Użu ma ’ vaċċini oħrajn
Administration of Gardasil at the same time (but, for injected vaccines, at a different injection site) as hepatitis B (recombinant) vaccine did not interfere with the immune response to the HPV types.
L- għoti ta ’ Gardasil fl- istess ħin (iżda, għal vaċċini injettati, f’ sit ta 'l- injezzjoni differenti) bħal vaċċin ta ’ l- epatite B (rikombinanti) ma jinterferixxix mar- rispons immuni għat- tipi HPV.
The seroprotection rates (proportion of subjects reaching seroprotective level anti-HBs > 10 mIU/ ml) were unaffected (96.5% for concomitant vaccination and 97.5% for hepatitis B vaccine only).
Ir- rati ta ’ seroprotezzjoni (proporzjon ta ’ suġġetti li jilħqu livell seroprotettiv anti- HBs > 10 mIU/ ml) ma kienux affettwati (96. 5% għal vaċinazzjoni konkomitanti u 97. 5% għal vaċċin ta ’ l- epatite B waħdu).
Anti-HBs geometric mean antibody titres were lower on co-administration, but the clinical significance of this observation is not known.
It- titres medji ġeometriċi ta ’ l- anti- korpi ta 'kontra l- HBs kienu inqas fl- għoti flimkien, iżda s- sinifikat kliniku ta ’ din l- osservazzjoni mhux magħruf.
The concomitant administration of Gardasil with vaccines other than hepatitis B (recombinant) vaccine has not been studied.
L- għoti fl- istess ħin ta ’ Gardasil ma ’ vaċċini oħrajn li mhumiex vaċċini ta ’ l- epatite B (rikombinanti) ma kienx studjat.
Use with hormonal contraceptives
Użu ma ’ kontraċettivi ormonali
In clinical studies, 57.5% of women (age 16 to 26 years) who received Gardasil used hormonal contraceptives.
Fi studji kliniċi, 57. 5% tan- nisa (ta ’ età bejn 16 u 26 sena) li rċivew Gardasil użaw kontraċettivi ormonali.
Use of hormonal contraceptives did not appear to affect the immune response to Gardasil.
Ma deherx li l- użu ta ’ kontraċettivi ormonali kellu effett fuq ir- rispons immuni għal Gardasil.
Specific studies of the vaccine in pregnant women were not conducted.
Ma sarux studji speċifiċi tal- vaċċin fuq nisa tqal.
During the clinical development program, 3,315 women (vaccine = 1,657 vs. placebo = 1,658) reported at least one pregnancy.
Matul il- programm ta ’ żvilupp kliniku, 3, 315- il mara (vaċċin = 1, 657 vs. plaċebo = 1, 658) irrappurtaw mill- inqas tqala waħda.
There were no significant differences in types of anomalies or proportion of pregnancies with an adverse outcome in Gardasil and placebo treated subjects.
Ma kien hemm ebda differenza sinifikanti f’ tipi ta ’ anomaliji jew proporzjonijiet ta ’ tqaliet b’ riżultat avvers f’ suġġetti ikkurati b’ Gardasil u f’ dawk ikkurati bi plaċebo.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/ foetal development, parturition or postnatal development (see section 5.3).
Studji fuq l- annimali ma jindikaw l- ebda effetti diretti jew indiretti li jagħmlu l- ħsara fuq it- tqala, l - iżvilupp ta 'l- embriju/ fetu, il- proċess tal- ħlas jew l- iżvilupp ta' wara t- twelid (ara sezzjoni 5. 3).
The data on Gardasil administered during pregnancy did not indicate any safety signal.
L- informazzjoni fuq Gardasil mogħti waqt it- tqala ma tindikax l- ebda sinjal tas- sigurtà.
However, these data are insufficient to recommend use of Gardasil during pregnancy.
Madankollu, din l- informazzjoni mhix biżżejjed biex ikun irrakkomandat l- użu ta ’ Gardasil waqt it- tqala.
Vaccination should, therefore, be postponed until completion of pregnancy.
Għalhekk, il- tilqima għandha tiġi posposta sakemm tintemm it- tqala.
In breastfeeding mothers given Gardasil or placebo during the vaccination period of the clinical trials the rates of adverse reactions in the mother and the breastfed infant were comparable between the vaccination and the placebo groups.
F’ nisa li kienu qed ireddgħu mogħtija Gardasil jew plaċebo waqt il- perjodu tat- tilqima tal- provi kliniċi, ir- rati ta ’ reazzjonijiet avversi fl- omm u fit- tarbija mredda ’ kienu komparabbli bejn il- gruppi tal- vaċinazzjoni u dawk tal- plaċebo.
In addition, vaccine immunogenicity was comparable among breastfeeding mothers and women who did not breastfeed during the vaccine administration.
Flimkien ma 'dan, l- immunoġeniċità tal- vaċċin kienet komparabbli fost l- ommijiet li kienu jreddgħu u n- nisa li ma kienux qed ireddgħu waqt l- għoti tal - vaċċin.
Therefore Gardasil can be given to breastfeeding women.
Għaldaqstant, Gardasil jista ’ jingħata lil nisa li jreddgħu.
4 In 5 clinical trials (4 placebo-controlled), subjects were administered Gardasil or placebo on the day of enrolment and approximately 2 and 6 months thereafter.
F’ 5 provi kliniċi (4 ikkontrollati bil- plaċebo), il- pazjenti ngħataw Gardasil jew il- plaċebo fil- jum tar - reġistrazzjoni u madwar xahrejn u 6 xhur wara dan.
Few subjects (0.2%) discontinued due to adverse reactions.
Ftit mill- pazjenti (0. 2%) waqqfu minħabba reazzjonijiet avversi.
The subjects who were monitored using VRC-aided surveillance included 6,160 subjects (5,088 females 9 to 26 years of age and 1,072 males 9 to 15 years of age at enrolment) who received Gardasil and 4,064 subjects who received placebo.
Is- sigurtà kienet evalwata jew fil- popolazzjoni studjata kollha (4 studji) jew f’ sett speċifiku definit minn qabel (studju wieħed) tal- popolazzjoni studjata bl- użu ta sorveljanza megħjuna b' kard ta ’ rappurtaġġ tat- tilqima (VRC) għal 14- il jum wara kull injezzjoni ta ’ Gardasil jew tal- plaċebo Il- pazjenti li kienu mmonitorjati bl- użu ta ’ sorveljanza megħjuna bil- VRC inkludew 6, 160 pazjent (5, 088 mara, ta ’ età bejn 9 u 26 sena, u 1, 072 raġel ta ’ età bejn 9 u 15- il sena fiż- żmien tar - reġistrazzjoni) li rċivew Gardasil u 4, 064 pazjent li rċevew il- plaċebo.
The following vaccine-related adverse reactions were observed among recipients of Gardasil at a frequency of at least 1.0% and also at a greater frequency than observed among placebo recipients.
Ir- reazzjonijiet avversi li ġejjin, li kienu marbuta mal- vaċċin, kienu osservati fost ir- reċipjenti ta ’ Gardasil fi frekwenza ta ’ mill- anqas 1. 0% u anke fi frekwenza akbar minn dik li kienet osservata fost ir- reċipjenti tal- plaċebo.
They are ranked under headings of frequency using the following convention:
Dawn huma kklassifikati taħt kategoriji ta 'frekwenza billi tintuża l - konvenzjoni li ġejja:
[Very Common (≥ 1/ 10); Common (≥ 1/ 100,  1/ 10); Uncommon (≥ 1/ 1,000,  1/ 100); Rare (≥ 1/ 10,000,  1/ 1,000); Very Rare ( 1/ 10,000), including isolated reports]
[Komuni Ħafna (≥ 1/ 10); Komuni (≥ 1/ 100, < 1/ 10); Mhux Komuni (≥ 1/ 1, 000, < 1/ 100); Rari (≥ 1/ 10, 000, < 1/ 1, 000); Rari Ħafna (< 1/ 10, 000), inklużi rapporti iżolati]
General disorders and administration site conditions:
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata Komuni ħafna: deni.
Very common: pyrexia.
Komuni ħafna:
Very common: at the injection site: erythema, pain, swelling.
Komuni:
Common: at the injection site: bruising, pruritus.
Fis- sit ta ’ l- injezzjoni: tbenġil, ħakk.
In addition, in clinical trials adverse reactions that were judged to be vaccine- or placebo-related by the study investigator were observed at frequencies lower than 1%:
Flimkien ma 'dan, fi provi kliniċi, kienu osservati reazzjonijiet avversi li kienu meqjusa mill - investigatur ta ’ l- istudju bħala li huma marbuta mal- vaċċin jew mal- plaċebo fi frekwenzi ta ’ inqas minn 1%:
Very rare: bronchospasm.
Rari ħafna: bronkospażmu.
Rare: urticaria.
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Rari: urtikarja.
Seven cases (0.06%) of urticaria were reported in the Gardasil group and 17 cases (0.18%) were seen in the adjuvant-containing placebo group.
Seba ’ każijiet (0. 06%) ta ’ urtikarja kienu rrappurtati fil- grupp ta 'Gardasil u 17- il każ (0. 18%) kienu osservati fil- grupp li kienet qed jingħata is- sustanza li kien fiha l- plaċebo.
In the clinical studies, subjects in the Safety Population reported any new medical conditions during the follow-up of up to 4 years.
Fi studji kliniċi, il- pazjenti fil- Popolazzjoni tas- Sigurtà rrappurtaw kwalunkwe kundizzjonijiet mediċi ġodda waqt il- follow- up sa 4 snin.
Among 11,778 subjects who received Gardasil and 9,686 subjects who received placebo, there were 28 cases of non-specific arthritis/ arthropathy reported, 20 in the Gardasil group and 8 in the placebo group.
Fost il- 11, 778 pazjent li rċivew Gardasil u 9, 686 pazjent li rċivew il- plaċebo, kien hemm 28 każ ta ’ artrite/ artropatija mhux speċifika li kienu rrappurtati, 20 fil- grupp ta ’ Gardasil u 8 fil- grupp tal- plaċebo.
Post Marketing Experience
Esperjenza ta ’ wara t- tqegħid fis- Suq
Post Marketing adverse events have been spontaneously reported for Gardasil and are not listed above.
Episodji avversi ta ’ wara t- tqegħid fis- suq ġew irrapportati b’ mod spontanju għal Gardasil u m’ humiex elenkati hawn fuq.
Because these events were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or to establish, for all events, a causal relationship to vaccine exposure.
Minħabba li dawn l- episodji ġew irrapportati b’ mod volontarju minn popolazzjoni ta ’ daqs inċert, mhuwiex possibbli li l- frekwenza tagħhom tkun stmata, jew sabiex tiġi stabbilita, f’ kull każ relazzjoni każwali għal espożizzjoni tal- vaċċin, b’ mod affidabbli.
Blood and lymphatic system disorders: lymphadenopathy.
Disturbi fid- demm u fis- sistema limfatika: limfadenopatija
Immune system disorders: hypersensitivity reactions including anaphylactic/ anaphylactoid reactions.
Disturbi fis- sistema immuni: reazzjonijiet ta ’ sensittività eċċessiva inkluż reazzjonijiet anafilattiċi/ anafilatojdi.
Guillain-Barré syndrome, dizziness, headache, syncope sometimes accompanied by tonic-clonic movements.
Disturbi fis- sistema nervuża: sindromu ta ’ Guillain- Barré, sturdament, uġigħ ta ’ ras, sinkope xi kultant akkompanjata b’ movimenti kloniċi toniċi.
Gastrointestinal disorders: nausea, vomiting.
5 Disturbi gastrointestinali: tqalligħ, remettar
Musculoskeletal and connective tissue disorders: arthralgia, myalgia.
Disturbi muskolu- skeltrali u tal- connective tissue: artralġja, uġigħ fil- muskoli
5 General disorders and administration site conditions: asthenia, fatigue, malaise.
Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata: astenja, għeja, telqa
There have been reports of administration of higher than recommended doses of Gardasil.
Kien hemm rapporti dwar l- għoti ta ’ doża ogħla mid- dożi rakkomandati ta ’ Gardasil.
In general, the adverse event profile reported with overdose was comparable to recommended single doses of Gardasil.
B’ mod ġenerali, il- profil ta ’ l- avvenimenti avversi rrapputati b’ doża eċċessiva kien komparabbli ma 'dak tad- doża waħidha rakkomandata ta ’ Gardasil.
Viral Vaccine, ATC code:
Vaċċin virali, kodiċi ATC:
Mechanism of Action
Mekkaniżmu ta ’ l- azzjoni:
Gardasil is an adjuvanted non-infectious recombinant quadrivalent vaccine prepared from the highly purified virus-like particles (VLPs) of the major capsid L1 protein of HPV types 6, 11, 16 and 18.
Gardasil huwa vaċċin mhux infettuż, rikombinanti, kwadrivalenti, adjuvanted ippreparat minn partikuli qishom virus- like particles (VLPs) ippurifikati ħafna tal- proteina maġġuri kapsida L1 tat- tipi ta ’ HPV 6, 11, 16 u 18.
The VLPs contain no viral DNA, they cannot infect cells, reproduce or cause disease.
Il- VLPs ma fihom l- ebda DNA virali, ma jistgħux jinfettaw iċ- ċelluli, jirriproduċu jew jikkawżaw mard.
HPV only infects humans, but animal studies with analogous papillomaviruses suggest that the efficacy of LI VLP vaccines is mediated by the development of a humoral immune response.
HPV jinfetta biss lill- bnedmin, iżda studji fuq l- annimali b' papillomaviruses simili jissuġġerixxu li l- effikaċja tal- vaċċini LI VLP tkun medjata bl- iżvilupp ta ’ rispons immuni umorali.
HPV 16 and HPV 18 are estimated to be responsible for approximately 70% of cervical cancers; 80% of adenocarcinoma in situ (AIS); 45-70% of high-grade cervical intraepithelial neoplasia (CIN 2/ 3); 25% of low grade cervical intraepithelial neoplasia (CIN 1); approximately 70% of HPV related high- grade vulvar (VIN 2/ 3) and vaginal (VaIN 2/ 3) intraepithelial neoplasia.
HPV 16 u HPV 18 huma stmati li huma responsabbli għal madwar 70% ta ’ kanċers ċervikali; 80% ta ’ adenokarċinoma in situ (AIS); 45- 70% ta ’ neoplasija intraepiteljali ċervikali ta ’ grad għoli (CIN 2/ 3); 25% ta ’ neoplasija intraepiteljali ċervikali ta ’ grad baxx (CIN 1); madwar 70% tan- neplasja intraepiteljali tal- vulva ta ’ grad għoli (VIN 2/ 3) u neplasja intraepiteljali vaġinali (VaIN 2/ 3).
HPV 6 and 11 are responsible for approximately 90% of genital warts and 10% of low grade cervical intraepithelial neoplasia (CIN 1).
HPV 6 u 11 huma responsabbli għal madwar ta ’ 90% tal- każijiet ta ’ felul ġenitali u 10% għal neoplasja intraepiteljali ċervikali ta ’ livell baxx (CIN 1).
CIN 3 and AIS have been accepted as immediate precursors of invasive cervical cancer.
CIN 3 u AIS ġew aċċettati bħala prekursuri immedjati ta ’ kanċer ċervikali invażiv.
The term "premalignant genital lesions" in section 4.1 corresponds to high-grade cervical intraepithelial neoplasia (CIN 2/ 3), high-grade vulvar intraepithelial neoplasia (VIN 2/ 3) and high- grade vaginal intraepithelial neoplasia (VaIN 2/ 3).
It- terminu "leżjonijiet ġenitali premalinni" f’ sezzjoni 4. 1 jikkorrespondi għal neoplasja intraepiteljali ċervikali ta ’ grad għoli (CIN 2/ 3), neoplasja intraepiteljali vulvari ta ’ grad għoli (VIN 2/ 3) u neoplasja intraepiteljali vaġinali ta ’ grad għoli (VaIN 2/ 3).
Clinical Studies
Studji Kliniċi
The efficacy of Gardasil was assessed in 4 placebo-controlled, double-blind, randomized Phase II and III clinical studies including a total of 20,541 16- to 26-year old women, who were enrolled and vaccinated without pre-screening for the presence of HPV infection.
L- effikaċja ta ’ Gardasil kienet evalwata f’ 4 provi kliniċi kkontrollati bil- plaċebo, double- blind, randomized ta ’ Fażi II u III, li kienu jinkludu total ta ’ 20, 541 mara ta ’ età ta 'bejn 16 u 26 sena, li kienu rreġistrati u vaċċinati mingħajr screening minn qabel, għall- preżenza ta ’ infezzjoni tal- HPV.
The primary efficacy endpoints included HPV 6-, 11-, 16-, or 18-related vulvar and vaginal lesions (genital warts, VIN, VaIN) and CIN of any grade (Protocol 013, FUTURE I), HPV 16- or 18-related CIN 2/ 3 and AIS (Protocol 015, FUTURE II), HPV 6-, 11-, 16-, or 18-related persistent infection (Protocol 007), and HPV 16-related persistent infection (Protocol 005).
Ir- riżultati aħħarin primarji ta ’ l- effikaċja inkludew feriti tal- vulva u tal- vaġina marbuta ma ’ HPV 6 -, 11 -, 16 -, jew 18 - (felul ġenitali, VIN, VaIN) u CIN ta ’ kwalunkwe grad (Protokoll 013, Futur I), CIN 2/ 3 marbuta ma ’ HPV 16 - jew 18 - u AIS (Protokoll 015, FUTUR II), infezzjoni persistenti marbuta ma ’ HPV 6 -, 11 -, 16 -, jew 18 (Protokoll 007), u infezzjoni persistenti marbuta ma ’ HPV 16 (Protokoll 005).
Efficacy results are presented for the combined analysis of study protocols.
Ir- riżultati ta ’ l- effikaċja huma ppreżentati għall- analiżi kkombinata ta ’ protokolli ta ’ studju.
The efficacy for HPV 16/ 18 related CIN 2/ 3 or AIS is based on data from protocols 005 (16-related endpoints only), 007, 013, and 015.
L - effikaċja għal CIN 2/ 3 jew AIS relatati ma ’ HPV 16/ 18 hija bbażata fuq tagħrif minn protokolli 005 (16- il- punt ta ’ tmiem relatat biss), 007, 013, u 015.
The efficacy for all other endpoints is based on protocols 007, 013, and 015.
L- effikaċja għall- punti ta ’ tmiem l- oħrajn kollha 6 hija bbażata fuq il- protokolli 007, 013, u 015.
The median duration of follow-up for these studies was 4.0, 3.0, 3.0, and 3.0 years for Protocol 005, Protocol 007, Protocol 013, and Protocol 015, respectively.
It- tul medjan tal- follow- up għal dawn l- istudji kien 4. 0, 3. 0, 3. 0, u 3. 0 snin għal Protokoll 005, Protokoll 007, Protokoll 013, u Protokoll 015, rispettivament.
The median duration of follow-up for the combined protocols (005, 007, 013, and 015) was 3.6 years.
It- tul medjan tal- follow- up għall- protokolli flimkien (005, 007, 013, and 015) kien 3. 6 snin.
Results of individual studies support the results from the combined analysis.
Ir- riżultati ta ’ studji individwali jappoġġjaw ir- riżultati mill- analiżi kkombinata.
Gardasil was efficacious against HPV disease caused by each of the four vaccine HPV type.
Gardasil kien effikaċji kontra l - mard tal- HPV ikkawżat minn kull wieħed mill- erba ’ tipi ta ’ vaċċin HPV.
At end of study, subjects enrolled in the two Phase-III studies (Protocol-013 and Protocol-015), were followed for up to 4 years (median 3.7 years).
Fl- aħħar tal- istudju, is - suġġetti rreġistrati fiż- żewġ studji ta ’ Fażi III (Protokoll 013 u Protokoll 015), ġew segwiti għal perjodu sa 4 snin (medjan 3. 7 snin).
6 Cervical Intraepithelial Neoplasia (CIN) Grade 2/ 3 (moderate to high-grade dysplasia) and adenocarcinoma in situ (AIS) were used in the clinical trials as a surrogate marker for cervical cancer.
In- Neoplasja Intraepiteljali Ċervikali (CIN) ta ’ Grad 2/ 3 (displasja moderata sa grad għoli) u adenokarċinoma in situ (AIS) intużaw fi provi kliniċi bħala indikazzjoni sostituttiva għall- kanċer ċervikali.
Prophylactic Efficacy against Vaccine HPV Types (HPV 6, 11, 16, or 18)
Effikaċja profilattika kontra Tipi ta ’ Vaċċini HPV (HPV 6, 11, 16 jew 18)
The primary analyses of efficacy, with respect to vaccine HPV types (HPV 6, 11, 16, and 18), were conducted in the per-protocol efficacy (PPE) population (n= all 3 vaccinations within 1 year of enrolment, no major protocol deviations and naïve to the relevant HPV type(s) prior to dose 1 and through 1 month Postdose 3 (Month 7)).
L- analiżi primarji ta ’ l- effikaċja, fir- rigward ta ’ tipi ta ’ vaċċini HPV (HPV 6, 11, 16, u 18), saru fil - popolazzjoni ta ’ l- effikaċja skond il- protokoll (PPE) (n= it- 3 tilqimiet kollha fi żmien sena mir - reġistrazzjoni, l- ebda devjazzjonijiet kbar mill- protokoll u naïve għat- tip( i) ta ’ HPV rilevanti qabel l- 1 doża u matul l- ewwel xahar tal- perjodu ta ’ Wara d- Doża 3 (Xahar 7)).
Efficacy was measured starting after the Month 7 visit.
L- effikaċja bdiet titkejjel wara ż- żjara ta 'Xahar 7.
Overall, 73% of subjects were naïve (PCR negative and seronegative) to all 4 HPV types at enrolment.
B’ kollox, waqt ir- reġistrazzjoni, 73% tal- pazjenti kienu naïve għall- 4 tipi kollha ta ’ HPV (negattivi għal PCR u seronegattivi).
Efficacy in subjects naïve to the relevant vaccine HPV type(s)
Effikaċja f’ suġġetti naïve għall- vaċċin rilevanti tat- tip( i) HPV
The efficacy results for relevant endpoints analysed at 2 years post-enrolment and at end of study (median duration of follow-up = 3.6 years) in the per-protocol population are presented in the Table 1.
Ir- riżultati ta ’ l- effikaċja għall- punti ta ’ tmiem relevanti analizzati fit- 2 sena wara r- reġistrazzjoni u fl - aħħar tal- istudju (tul medjan tal- follow- up = 3. 6 snin) huma ppreżentati f’ Tabella 1.
In a supplemental analysis, the efficacy of Gardasil was evaluated against HPV 16/ 18-related CIN 3 and AIS.
F’ analiżi supplimentali, l- effikaċja ta ’ Gardasil ġiet evalwata kontra CIN 3 u AIS relatati ma ’ HPV 16/ 18
Analysis of efficacy of Gardasil against high grade cervical lesions in the PPE population
Analiżi ta 'l- effikaċja ta' Gardasil kontra leżjonijiet ċervikali ta ’ grad għoli fil - popolazzjoni PPE
Placebo Gardasil
Gardasil
Number Number
Numru
% Number
Numru
Number
Numru%
Efficacy***
Numru
of cases of cases
Effikaċja ***
Efficacy of cases
ta ’ ta ’
of cases
ta ’ Effikaċja
at end of
ta ’
Number Number
fl- aħħar tal -
at 2 years Number
każijiet każijiet
Number Number at 2 years Number Number
każijiet f’ sena 2
study
każijiet
of of
istudju
of of (95% CI) of of
Numru Numru Numru Numru ta ’ ta ’ ta ’ ta ’
subjects* subjects*
suġġetti * suġġetti *
subjects* subjects*
suġġetti * 100. 0
HPV 16/ 18-related
suġġetti *
0 53
98. 2
98.2
(92. 9,
CIN 2/ 3 or AIS
(93. 5, 99. 8)
(93.5, 99.8)
100. 0) 16/ 18
HPV 16/ 18-related CIN 3
CIN 3 relatata ma ’
100 (86.5, 100.0)
(88. 4, 99. 6)
96.9 (88.4, 99.6)
100. 0)
HPV 16/ 18-related
AIS relatata ma ’
100
(14. 8,
*Number of subjects with at least one follow-up visit after Month 7 **Based on virologic evidence, this CIN 3 case in a patient chronically infected with HPV 52 is likely to be causally related to HPV 52.
100. 0) * Numru ta ’ suġġetti b’ għallinqas żjara ta ’ follow- up waħda wara Xahar 7 ** Abbażi ta ’ evidenza viroloġika, dan il- każ ta ’ CIN 3 f’ pazjent infettat kronikament b’ HPV 52 x’ aktarx li huwa każwalment relatat ma ’ HPV 52.
In only 1 of 11 specimens HPV 16 was found (at Month 32.5) and was not detected in tissue excised during LEEP (Loop Electro-Excision Procedure).
Jekk instab kampjun 1 biss mill- 11- il kampjuni HPV 16 (f’ Xahar 32. 5) u dan ma ġiex relevant fit- tessut maqtugħ matul LEEP (Loop Electro- Excision Procedure).
In the second CIN 3 case observed in a patient infected with HPV 51 at Day 1 (in 2 of 9 specimens); HPV 16 was detected at a Month 51 biopsy (in 1 of 9 specimens) and HPV 56 was detected in 3 of 9 specimens at Month 52 in tissue excised during LEEP. ***Patients were followed for up to 4 years (median 3.6 years) Note:
Fit- tieni każ ta ’ CIN 3 osservat f’ pazjent infettat b’ HPV 51 f’ Jum 1 (fi 2 minn 9 kampjuni); HPV 16 ġie rilevat f’ bijopsija wara Xahar 51 (f’ 1 minn 9 kampjuni) u HPV 56 ġie rilevat fi 3 minn 9 kampjuni wara Xahar 52 f’ tessut imneħħi waqt LEEP. *** Il- pazjenti ġew segwiti sa perjodu ta ’ 4 snin (medjan 3. 6 snin) Nota:
Point estimates and confidence intervals are adjusted for person-time of follow-up.
Stimi tal- punti u intervalli ta ’ kunfidenza huma aġġustati għal persuna- ħin ta ’ follow- up.
At end of study and in the combined protocols,
7 Fl- aħħar tal- istudju u fil- protokolli kombinati,
the efficacy of Gardasil against HPV 6-, 11-, 16-, 18-related CIN 1 was 95.9% (95% CI:
91. 4, 98. 4)
91.4, 98.4) the efficacy of Gardasil against HPV 6-, 11-, 16-, 18-related CIN (1, 2, 3) or AIS was 96.0% (95% CI:
l- effikaċja ta ’ Gardasil kontra CIN (1, 2, 3) jew AIS relatata ma ’ HPV 6 -, 11 -, 16 -, 18 - kienet 96. 0% (95% CI:
92.3, 98.2)
92. 3, 98. 2)
the efficacy of Gardasil against HPV 6-, 11-, 16-, 18-related VIN2/ 3 and VaIN 2/ 3 was 100% (95% CI:
l- effikaċja ta ’ Gardasil kontra VIN2/ 3 u VaIN 2/ 3 relatata ma ’ HPV 6 -, 11 -, 16 -, 18 kienet 100% (95% CI:
67.2, 100) and 100% (95% CI:
67. 2, 100) u 100% (95% CI:
55.4, 100) respectively
55. 4, 100) rispettivament
7 the efficacy of Gardasil against HPV 6-, 11-, 16-, 18-related genital warts was 99.0% (95% CI:
l- effikaċja ta ’ Gardasil kontra felul ġenetali relatat ma ’ HPV 6 -, 11 -, 16 -, 18 kienet 99. 0% (95% CI:
96.2,99.9).
96. 2, 99. 9)
In Protocol 012 the efficacy of Gardasil against the 6 month definition of persistent infection [samples positive on two or more consecutive visits 6 months apart (±1 month) or longer] related to HPV 16 was 98.7% (95% CI:
Fi Protokoll 012, l- effikaċja ta ’ Gardasil kontra d- definizzjoni ta ’ 6 xhur ta ’ infezzjoni persistenti [kampjuni pożittivi fuq żewġ żjarat konsekuttivi jew aktar b’ 6 xhur bejniethom (±1 xahar) jew aktar] relatati ma ’ HPV 16 kienet 98. 7% (95% CI:
95.1, 99.8) and 100.0% (95% CI:
95. 1, 99. 8) u 100. 0% (95% CI:
93.2, 100.0) for HPV 18 respectively, after a follow-up of up to 4 years (mean of 3.6 years).
93. 2, 100. 0) għal HPV 18 rispettivament, wara follow- up ta ’ massimu ta ’ 4 snin (medja ta ’ 3. 6 sena).
For the 12 month definition of persistent infection, efficacy against HPV 16 was 100.0% (95% CI:
Għad- definizzjoni ta ’ 12- il xahar ta ’ infezzjoni persistenti, l- effikaċja kontra HPV 16 kienet 100. 0% (95% CI:
93.9, 100.0) and 100.0% (95% CI:
93. 9, 100. 0) u 100. 0% (95% CI:
79.9, 100.0) for HPV 18 respectively.
79. 9, 100. 0) għal HPV 18 rispettivament.
Efficacy in individuals with evidence of HPV 6, 11, 16, or 18 infection or disease at day 1
Effikaċja f’ individwi b’ evidenza ta ’ infezzjoni jew marda b’ HPV 6, 11, 16 jew 18 f’ jum 1.
There was no evidence of protection from disease caused by vaccine HPV types for which subjects were PCR positive at day 1.
Ma kien hemm l- ebda evidenza ta ’ protezzjoni mill- marda kkawżata minn tipi HPV ta ’ vaċċin li għalihom il- pazjenti kienu PCR pożittivi f’ jum 1.
Individuals who were already infected with one or more vaccine-related HPV types prior to vaccination were protected from clinical disease caused by the remaining vaccine HPV types.
Individwi li diġà kienu infettati b’ xi tip ta ’ HPV marbut mal- vaċċin qabel il- tilqima, kienu protetti mill- mard kliniku kkawżat mill- bqija tat- tipi ta ’ HPV tal- vaċċin.
Efficacy in subjects with and without prior infection or disease due to HPV 6, 11, 16, or 18
L- effikaċja f’ suġġetti bi jew mingħajr infezzjoni jew marda dovuta għal HPV 6, 11, 16 jew 18.
The modified intention to treat (ITT) population included women regardless of baseline HPV status at Day 1, who received at least one vaccination and in whom case counting started at 1 month Postdose 1.
L- intenzjoni mibdula biex tikkura popolazzjoni (ITT) inkludiet nisa irrispettivament mill- istat tal- linja bażi ta ’ HPV f’ Jum 1, li rċievew ta ’ l- inqas tilqima waħda u li fihom, l- għadd tal- każijiet beda jsir fl - ewwel xahar Wara d- Doża 1.
This population approximates to the general population of women with respect to prevalence of HPV infection or disease at enrolment.
Din il- popolazzjoni toqrob lejn il- popolazzjoni ġenerali tan- nisa fir - rigward tal- prevalenza ta ’ infezzjoni u mard b’ HPV fil- ħin tar- reġistrazzjoni.
The results are summarised in Table 2.
Tabella 2:
Efficacy of Gardasil in high grade cervical lesions in the modified ITT-population including women regardless of baseline HPV status
L- effikaċja ta ’ Gardasil f’ leżjonijiet ċervikali ta ’ grad għoli fil- popolazzjoni ITT mibdula li tinkludi nisa irrispettivament mill- istat tal- linja bażi ta ’ HPV
Number of Number
Numru ta ’ Numru
% Number
Numru%
Efficacy**
Effikaċja **
cases
ta ’
of cases
ta ’
Efficacy** of cases
ta ’
of cases
każijiet
at end of
Effikaċja **
Number of Number
fl- aħħar
at 2 years Num
każijiet
Number of Number at 2 years Number Number
każijiet f’ sena 2
subjects*
Numru ta ’
of
(95% CI)
(95% CI) of of
tal- istudju
of (95% CI) of of
suġġetti *
(95% CI)
Numru ta ’
subjects* subjects*
Numru Numru ta ’ ta ’
18-related CIN 2/ 3 or AIS
(23. 3, 51. 7)
(41.1, 60.7)
46. 0
HPV 16/ 18- related CIN 3
CIN 3 relatata
34.3 (12.7, 50.8)
(12. 7, 50. 8)
46.0 (31.0, 57.9)
Numru ta ’ Numru
HPV 16/ 18-
suġġetti *
6
15 6
15
(< 0, 87. 6)
60.0
(< 0, 87. 3)
related AIS
HPV 16/ 18
*Number of subjects with at least one follow-up visit after 30 days after Day 1 **Percent efficacy is calculated from the combined protocols.
* Numru ta ’ suġġetti b’ għallinqas żjara ta ’ follow- up waħda wara 30 jum wara Jum 1 ** L- effikaċja perċentwali hija kkalkolata mill- protokolli kkombinati.
The efficacy for HPV 16/ 18 related CIN 2/ 3 or AIS is based on data from protocols 005 (16-related endpoints only), 007, 013, and 015.
L- effikaċja għal CIN 2/ 3 jew AIS relatat ma ’ HPV 16/ 18 hija bbażata fuq it- tagħrif mill- protokolli 005 (16- il punt ta ’ tmiem relatat biss), 007, 013 u 015.
Patients were followed for up to 4 years (median 3.6 years).
Il- pazjenti ġew segwiti sa perjodu ta ’ 4 snin (medjan 3. 6 snin).
Note: point estimates and confidence intervals are adjusted for person-time of follow-up.
Stimi ta ’ punti u intervalli ta ’ kunfidenza huma aġġustati għal persuna- ħin ta ’ follow- up.
Efficacy against HPV 6-, 11-, 16-, 18-related VIN 2/ 3 was 73.3% (95% CI:
L- effikaċja kontra VIN 2/ 3 relatata ma ’ HPV 6 -, 11 -, 16 -, 18 kienet ta ’ 73. 3% (95% CI:
40.3, 89.4), against HPV 6-, 11-, 16-, 18-related VaIN 2/ 3 was 85.7% (95% CI:
40. 3, 89. 4), kontra VaIN 2/ 3 relatata ma ’ HPV 6 -, 11 -, 16 -, 18 - li kienet 85. 7% (95% CI:
37.6, 98.4), and against HPV 6-, 11-, 16-, 18- related genital warts was 80.3% (95% CI:
37. 6, 98. 4), u kontra felul ġenitali relatat ma ’ HPV 6 -, 11 -, 16 -, 18 li kienet 80. 3% (95% CI:
73.9, 85.3) in the combined protocols at end of study.
73. 9, 85. 3) fil- protokolli kkombinati fl- aħħar tal- istudju.
Overall 12% of the combined study population had an abnormal Pap test suggestive of CIN at Day 1.
B’ kollox, 12% tal- popolazzjoni konġunta li kienet studjata kellha test anormali tal- Pap li jissuġġerixxi li kien hemm CIN f’ Jum 1.
Among subjects with an abnormal Pap test at Day 1 who were naïve to the relevant vaccine HPV types at Day 1, efficacy of the vaccine remained high.
Fost suġġetti li kellhom test anormali tal- Pap f’ Jum 1 li kienu naïve għat - tipi tal- vaċċin HPV rilevanti f’ Jum 1, l- effikaċja tal- vaċċin baqgħet għolja.
Among subjects with an abnormal Pap test at Day 1 who were already infected with the relevant vaccine HPV types at Day 1, no vaccine efficacy was observed.
Fost pazjenti li kellhom test anormali tal- Pap f’ Jum 1 li kienu diġà infettati bit- tipi tal- vaċċin HPV rilevanti f’ Jum 1, l- ebda effikaċja tal- vaċċin ma kienet osservata.
8 Protection Against the Overall Burden of Cervical HPV disease in 16- Through 26-Year-Old Women
Protezzjoni Kontra l- Piż Globali tal- marda HPV Ċervikali f’ Nisa ta ’ Bejn 16 u 26 Sena
The impact of Gardasil against the overall risk for cervical, HPV disease (i. e., disease caused by any HPV type) was evaluated starting 30 days after the first dose in 17,599 subjects enrolled in the two phase III efficacy trials (Protocols 013 and 015).
L- impatt ta ’ Gardasil kontra r- riskju globali għal mard HPV (jiġifieri mard ikkawżat minn kwalunkwe tip ta ’ HPV) ġie evalwat wara 30 jum mill- ewwel doża fi 17, 599 suġġett reġistrati fiż- żewġ provi ta ’ l - effikaċja ta ’ fażi III (Protokolli 013 u 015).
Among subjects who were naïve to 14 common HPV types and had a negative Pap test at Day 1, administration of Gardasil reduced the incidence of CIN 2/ 3 or AIS caused by vaccine- or non-vaccine HPV types by 42.7% (95% CI:
Fost is- suġġetti li kienu naïve għal 14- il tip komuni ta ’ HPV u li kellhom test Pap negattiv f’ Jum 1, l- amministrazzjoni ta ’ Gardasil naqset l- inċidenza ta ’ CIN 2/ 3 jew AIS ikkawżati minn tipi ta ’ HPV ta ’ vaċċin jew mhux vaċċin b’ 42. 7% (95% CI:
23.7, 57.3) and of genital warts by 82.8% (95% CI:
23. 7, 57. 3) u ta ’ felul ġenitali b’ 82. 8% (95% CI:
74.3, 88.8)at end of study.
74. 3, 88. 8) fl- aħħar tal- istudju.
In the modified ITT population, the benefit of the vaccine with respect to the overall incidence of CIN 2/ 3 or AIS (caused by any HPV type) and of genital warts was much lower, with a reduction of 18.4% (95% CI:
Fil- popolazzjoni ITT mibdula, il- benefiċċju tal- vaċċin fir- rigward ta ’ l- inċidenza globali ta ’ CIN 2/ 3 jew AIS (ikkawżata minn kwalunkwe tip ta ’ HPV) u ta ’ felul ġenitali kien ferm inqas, bi tnaqqis ta ’ 18. 4% (95% CI:
7.0, 28.4) and 62.5% (95% CI:
7. 0, 28. 4) u 62. 5% (95% CI:
54.0, 69.5), respectively, as Gardasil does not impact the course of infections or disease that are present at vaccination onset.
54. 0, 69. 5), rispettivament, minħabba li Gardasil ma għandux impatt fuq il- kors ta ’ l- infezzjonijiet jew mard li jfeġġu mal- bidu tat- tilqima.
Impact on Definitive Cervical Therapy Procedures
Impatt fuq Proċeduri ta ’ Terapija Ċervikali Definittivi
The impact of Gardasil on rates of Definitive Cervical Therapy Procedures regardless of causal HPV types was evaluated in 18,150 subjects enrolled in Protocol 007, Protocols 013 and 015.
L- impatt ta ’ Gardasil fuq ir- rati ta ’ Proċeduri ta ’ Terapija Ċervikali Definittivi irrispettivament mit- tipi ta ’ HPV kawżali kien evalwat fi 18, 150 suġġett reġistrati fil- Protokoll 007, Protokolli 013 u 015.
In the HPV naïve population (naïve to 14 common HPV types and had a negative Pap test at Day 1), Gardasil reduced the proportion of women who experienced, a definitive cervical therapy procedure (Loop Electro-Excision Procedure or Cold-Knife Conization) by 41.9% (95% CI:
Fil - popolazzjoni naïve għall- HPV( naïve għal 14- il tip ta ’ HPV komuni u li kellhom test Pap negattiv f’ Jum 1), Gardasil naqqas il- proporzjon ta ’ nisa li esperjenzaw, proċedura ta ’ terapija ċervikali definittiva (Loop Electro- Excision Procedure jew Cold- Knife Conization) b’ 41. 9% (95% CI:
27.7, 53.5) at end of study.
27. 7, 53. 5) fl- aħħar tal- istudju.
In the ITT population the corresponding reduction was 23.9% (95% CI:
Fil- popolazzjoni ITT, it- tnaqqis korrespondenti kien 23. 9% (95% CI:
15.2, 31.7).
15. 2, 31. 7).
Cross-protective efficacy The efficacy of Gardasil against CIN (any grade) and CIN 2/ 3 or AIS caused by 10 non-vaccine HPV types (HPV 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) structurally related to HPV 16 or HPV 18 was evaluated in the combined Phase III efficacy database (N = 17,599) after a median follow-up of 3.7 years (at end of study).
Effikaċja kross- protettiva L- effikaċja ta ’ Gardasil kontra CIN (kull grad) u CIN 2/ 3 jew AIS ikkawżati minn 10 tipi ta ’ HPV mhux vaċċin (HPV 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) strutturalment relatati ma ’ HPV 16 jew ma ’ HPV 18, ġiet evalwata fid- database kombinata ta ’ l- effikaċja ta ’ Fażi III (N = 17, 599) wara follow- up medjan ta ’ 3. 7 snin (fl- aħħar ta ’ l- istudju).
Efficacy against disease endpoints caused by pre-specified combinations of non-vaccine HPV types was measured.
L- effikaċja kontra punti ta ’ tmiem tal- marda ikkawżata 9 minn kombinazzjonijiet pre- speċifikati ta ’ tipi HPV tal- vaċċin ġiet imkejla.
The studies were not powered to assess efficacy against disease caused by individual HPV types.
L- istudji ma kinux mgħammra biex jivvalutaw l- effikaċja kontra mard ikkawżat minn tipi ta ’ HPV individwali.
The primary analysis was done in type-specific populations that required women to be negative for the type being analyzed, but who could be positive for other HPV types (96% of the overall population).
L- analiżi primarja saret f’ popolazzjonijiet speċifiċi għat- tip li ħtieġu li n- nisa jkunu negattivi għat- tip li kien qiegħed jiġi analizzat, iżda li setgħu kienu pożittivi għal tipi ta ’ HPV oħrajn (96% tal - popolazzjoni ġenerali).
The primary time point analysis after 3 years did not reach statistical significance for all pre-specified endpoints.
L- analiżi primarja tal- punt ta ’ tmiem wara 3 snin ma laħqitx sinifikat statistiku għall- punti ta ’ tmiem pre- speċifikati kollha.
The final end-of-study results for the combined incidence of CIN 2/ 3 or AIS in this population after a median follow-up of 3.7 years are shown in Table 3.
Ir- riżultati finali ta ’ l- aħħar ta ’ l- istudju għall- inċidenza kombinata ta ’ CIN 2/ 3 jew AIS f’ din il- popolazzjoni wara follow- up medjan ta ’ 3. 7 snin huma murija fit- Tabella 3.
For composite endpoints, statistically significant efficacy against disease was demonstrated against HPV types phylogenetically related to HPV 16 (primarily HPV 31) whereas no statistically significant efficacy was observed for HPV types phylogenetically related to HPV 18 (including HPV 45).
Għal punti ta ’ tmiem komposti, l- effikaċja b’ sinjifikat statistiku kontra l- marda ntweriet kontra tipi ta ’ HPV relatati filoġenetikament għal HPV 16 (primarjament HPV 31) billi ebda effikaċja li hija statistikament sinjifikanti ma ġiet osservata għal tipi ta ’ HPV filoġenetikament relatati ma ’ HPV 18 (inkluż HPV 45).
For the 10 individual HPV types, statistical significance was only reached for HPV 31.
Għal 10 tipi ta ’ HPV individwali, is- sinjifikat statistiku intlaħaq biss għal HPV 31.
Results for CIN 2/ 3 or AIS in Type-Specific HPV-Naïve Subjects † (end of study results) Naïve to ≥ 1 HPV Type
Riżultati għal CIN 2/ 3 jew AIS f’ Suġġetti naïve għall- HPV Speċifiku għat- Tip † (riżultati ta ’ tmiem l- istudju) Naïve għal ≥ Tip ta ’ HPV 1
Gardasil
Każijiet ta ’
Placebo
Każijiet ta ’
Composite Endpoint
Punt ta ’ tmiem kompost
cases
Gardasil
cases
plaċebo
% Efficacy
% Effikaċja
43.2%
43. 2%
12.1, 63.9
12. 1, 63. 9
(HPV 31/ 33/ 45/ 52/ 58) § 10 non-vaccine HPV Types ║
(HPV 31/ 33/ 45/ 52/ 58) § 10 tipi ta ’ HPV mhux vaċċin║
25.8% 23.0%
25. 8% 23. 0%
4.6, 42.5 5.1, 37.7
4. 6, 42. 5 5. 1, 37. 7
HPV-16 related types (A9 species)
Tipi relatati ma ’ HPV- 16 (speċi A9)
29.1%
29. 1%
9.1, 44.9
9. 1, 44. 9
HPV HPV HPV HPV HPV
26. 2, 74. 1 †
23 29 13 44 24
29
55.6% 19.1% 13.0% 14.7% 31.5%
< 0, 44. 2 †
26.2, 74.1† < 0, 52.1† < 0, 61.9 † < 0, 44.2† < 0, 61.0†
< 0, 61. 0 †
HPV-18 related types (A7 species)
58
34
24 34
46
35 46
25.9%
HPV 45
< 0, 53.9
0. 0%
37.5% 0.0% 39.9%
39. 9%
< 0, 69.5† < 0, 60.7† < 0, 76.8†
< 0, 48. 5 †
species (HPV 51)
Speċi A5 (HPV 51)
< 0, 48.5†
< 0, 32. 5 †
A6 species (HPV 56) †
Speċi A6 (HPV 56) †
-13.7%
- 13. 7%
The studies were not powered to assess efficacy against disease caused by individual HPV types. ‡ Efficacy was based on reductions in HPV 31-related CIN 2/ 3 or AIS § Efficacy was based on reductions in HPV 31-, 33-, 52-, and 58-related CIN 2/ 3 or AIS ║ Includes assay-identified non-vaccine HPV types 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59.
L- istudji ma kinux mgħammra biex jivvalutaw l- effikaċja kontra marda kkawżata minn tipi ta ’ HPV individwali. ‡ L- effikaċja kienet ibbażata fuq tnaqqis f’ CIN 2/ 3 jew AIS relatati ma ’ HPV 31 § L- effikaċja kienet ibbażata fuq tnaqqis f’ CIN 2/ 3 jew AIS relatati ma ’ HPV 31 -, 33 -, 52 -, u 58 ║ Tinkludi tipi ta ’ HPV mhux vaċċin identifikati mill- assaġġ 31, 33, 35, 39, 45, 51, 52, 56, 58, u 59.
Assays to Measure Immune Response
Assaġġi biex Jitkejjel ir- Rispons Immuni
No minimum antibody level associated with protection has been identified for HPV vaccines.
L- ebda livell ta ’ anti- korpi minimu marbut mal- protezzjoni ma kien identifikat għall- vaċċini HPV.
The immunogenicity of Gardasil was assessed in 8,915 (Gardasil n = 4,666; placebo n = 4,249) women 18 to 26 years of age and 3,400 female (Gardasil n = 1,471; placebo n = 583) and male (Gardasil n = 1,071; placebo n = 275) adolescents 9 to 17 years of age.
L- immunoġeniċità ta ’ Gardasil kienet evalwata fi 8, 915- il mara (Gardasil n = 4, 666; plaċebo n = 4, 249) ta ’ età bejn 18 u 26 sena u fi 3, 400 mara (Gardasil n = 1, 471; plaċebo n = 583) u raġel (Gardasil n = 1, 071; plaċebo n = 275) adolexxenti ta ’ età bejn 9 u 17- il sena.
Type-specific immunoassays, competitive Luminex-based immunoassay (cLIA), with type-specific standards were used to assess immunogenicity to each vaccine type.
Immunoassaġġi speċifiċi għat- tip, immunoassaġġi kompetittivi bbażati fuq Luminex (cLIA), bi standards speċifiċi għat- tip intużaw biex tiġi evalwata l- immunoġeniċità għal kull tip ta ’ vaċċin.
This assay measures antibodies against a single neutralizing epitope for each individual HPV type.
Dan l - assaġġ ikejjel l- anti- korpi kontra epitopu newtralizzanti wieħed għal kull tip individwali ta ’ HPV.
In the clinical studies, 99.9%, 99.8%, 99.8%, and 99.6% of individuals who received Gardasil became anti-HPV 6, anti-HPV 11, anti-HPV 16, and anti-HPV 18-seropositive respectively, by 1 month Postdose 3 across all age groups tested.
Risponsi Immuni għal Gardasil 10 Fl- istudji kliniċi, 99. 9%, 99. 8%, 99. 8%, u 99. 6% ta ’ l- individwi li rċivew Gardasil saru seropożittivi għal anti- HPV 6, anti- HPV 11, anti- HPV 16, u anti- HPV 18, rispettivament, sa żmien xahar Wara d - Doża 3 fost il- gruppi ta ’ etajiet kollha li kienu ttestjati.
Gardasil induced high anti-HPV Geometric Mean Titres (GMTs) 1 month Postdose 3 in all age groups tested.
Gardasil wassal għal Titres Medji Ġeometriċi (Geometric Mean Titres - GMTs) għoljin ta ’ kontra l- HPV xahar Wara d- Doża 3 fil- gruppi ta ’ etajiet kollha li kienu ttestjati.
Anti-HPV levels in placebo subjects who had cleared an HPV infection (seropositive and PCR negative) were substantially lower than those induced by the vaccine.
Il- livelli ta ’ l- anti- HPV fis- suġġetti li ħadu l- plaċebo li kienu eliminaw infezzjoni HPV (seropożittiva u negattiva għal PCR) kienu sostanzjalment inqas minn dawk ikkawżati mill- vaċċin.
Furthermore, anti-HPV levels (GMTs) in vaccinated subjects remained at or above serostatus cut-off during the long-term follow-up of the phase III studies (see below under Persistence).
Aktar minn hekk, il- livelli ta ’ l- anti- HPV (GMTs) fis- suġġetti vaċċinati baqgħu fil- livell tal- qtugħ il- linja ta ’ serostatus jew ogħla matul il- follow- up fuq tul ta 'żmien, ta ’ l- istudji ta ’ fażi III (ara taħt, fis- sezzjoni Persistenza).
10 Bridging the Efficacy of Gardasil from Young Adult Women to Young Adolescents
Ħolqien ta ’ Pont fl- Effikaċja ta ’ Gardasil minn Nisa Żgħażagħ Adulti sa Adolexxenti Żgħar
A clinical study (Protocol 016) compared the immunogenicity of Gardasil in 10- to 15-year-old boys and girls to those in 16- to 23-year old adolescent and young women.
Studju kliniku (Protokoll 016) qabbel l- immunoġeniċità ta ’ Gardasil f’ subien u bniet li kellhom minn 10 sa 15- il sena ma ’ dik f’ nisa adolexxenti u żgħażagħ ta ’ età bejn 16 u 23 sena.
In the vaccine group, 99.1 to 100% became seropositive to all vaccine serotypes by 1 month Postdose 3.
Fil- grupp bil- vaċċin, 99. 1 sa 100% saru seropożittivi għas- serotipi kollha tal- vaċċin sa xahar Wara d- Doża 3.
Table 4 compares the 1 month Postdose 3 anti-HPV 6, 11, 16, and 18 GMTs in 9- to 15-year-old boys and girls with those in 16- to 26-year old young women.
Tabella 4 tqabbel l- anti- HPV 6, 11, 16 u 18 GMTs xahar Wara d- Doża 3 f’ subien u bniet ta ’ bejn 9 u 15- il sena ma ’ dawk f’ nisa żgħażagħ ta ’ età bejn 16 u 26 sena.
Immunogenicity bridging between 9- to 15-year-old male and female subjects and 16- to 26-year-old adult women (per-protocol population) based on titres as measured by cLIA
Ħolqien ta ’ pont ta 'l- immunoġeniċità bejn pazjenti subien ta' bejn 9 u 15- il sena u nisa adulti ta 'bejn 16 u 26 sena (skond il- popolazzjoni tal- protokoll) ibbażat fuq titres kif imkejla minn cLIA
9- to 15-Year-Old Males (Protocols 016 and 018) n GMT (95% CI)
Subien bejn 9 u 15- il sena (Protokolli 016 u 018) n GMT (95% CI)
9- to 15-Year-Old Females 16- to (Protocols 016 and 018) n GMT (95% CI)
Bniet bejn 9 u 15- il sena (Protokolli 016 u 018) n GMT (95% CI)
26-Year-Old Females (Protocols 013 and 015) n GMT (95% CI)
Nisa bejn 16 u 26 sena (Protokolli 013 u 015) n GMT (95% CI)
GMT- Geometric mean titre in mMU/ ml (mMU = milli-Merck units)
GMT - Titres Medji Ġeometriċi f' mMU/ ml (mMU=unitajiet milli- Merck)
Anti-HPV responses at Month 7 among 9- to 15-year-old girls and boys were non-inferior to anti-HPV responses in 16- to 26-year-old young women for whom efficacy was established in the phase III studies.
Ir- risponsi anti- HPV f' Xahar 7 fost bniet ta 'bejn 9 u 15- il sena kienu mhux inferjuri għar- risponsi anti - HPV f' nisa żgħażagħ ta' bejn 16 u 26 sena li għalihom l- effikaċja kienet stabbilita fl- istudji ta 'fażi III.
Immunogenicity was related to age and Month 7 anti-HPV levels were significantly higher in younger individuals below 12 years of age than in those above that age.
L- immunoġeniċità kienet marbuta ma 'l- età u livelli anti- HPV mkejla f' Xahar 7 kienu ogħla b' mod sinifikattiv f' individwi iżgħar li kellhom taħt it- 12- il sena milli f' dak li kellhom iktar minn dik l- età.
On the basis of this immunogenicity bridging, the efficacy of Gardasil in 9- to 15-year-old girls is inferred.
Fuq bażi ta ’ l- ħolqien ta ’ pont ta ’ l- immunoġeniċità, l- effikaċja ta 'Gardasil fi bniet ta ’ bejn 9 u 15- il sena hija inferita.
Immunogenicity and safety of Gardasil have been demonstrated in 9- to 15-year-old boys.
L- immunoġeniċità u s- sigurtà ta ’ Gardasil intweriet f’ subien ta ’ bejn 9 u 15- il sena.
Protective efficacy has not been evaluated in males.
L- effikaċja protettiva ma kienitx evalwata fl- irġiel.