Clinical Trial Results:
A phase IIIb, open-label, multi-centre immunization study to evaluate the safety of GSK Biologicals’ HPV-16/18 L1 VLP AS04 vaccine administered intramuscularly according to a 0, 1, 6-month schedule in healthy female subjects who received the placebo control in the GSK HPV-015 study.
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Summary
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EudraCT number |
2010-020227-48 |
Trial protocol |
PT |
Global end of trial date |
10 Jan 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Jan 2018
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First version publication date |
07 Jan 2018
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
113618
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01249365 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GlaxoSmithKline Biologicals
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Sponsor organisation address |
Rue de l’Institut 89, Rixensart, Belgium, B-1330
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Public contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com
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Scientific contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
23 May 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
10 Jan 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Jan 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the safety of the HPV-16/18 L1 VLP AS04 vaccine throughout the study period.
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Protection of trial subjects |
The vaccinees were observed closely for at least 30 minutes, with appropriate medical treatment readily available in case of anaphylaxis following the administration of vaccine.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
24 Jan 2011
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
6 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Australia: 32
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Country: Number of subjects enrolled |
Portugal: 54
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Country: Number of subjects enrolled |
Russian Federation: 32
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Country: Number of subjects enrolled |
Singapore: 81
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Worldwide total number of subjects |
199
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EEA total number of subjects |
54
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
196
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were recruited from 16 centers in total, located in 4 countries: Australia, Portugal, Russian Federation and Singapore. | ||||||||||
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Pre-assignment
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Screening details |
All subjects were included in the trial. | ||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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HPV vaccine | ||||||||||
Arm description |
Healthy female subjects aged 26 years and above, who received control vaccine in the primary study NCT00294047, were administrated 3 intramuscular injections of Cervarix vaccine into the deltoid of the non-dominant arm, according to a 0, 1, 6-month schedule in the current study. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Cervarix
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Investigational medicinal product code |
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Other name |
GSK Biologicals’ HPV-16/18 L1 VLP AS04 vaccine
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Subjects received three doses of the study vaccine administered intramuscularly according to a 0, 1, 6-month schedule.
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Baseline characteristics reporting groups
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Reporting group title |
HPV vaccine
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Reporting group description |
Healthy female subjects aged 26 years and above, who received control vaccine in the primary study NCT00294047, were administrated 3 intramuscular injections of Cervarix vaccine into the deltoid of the non-dominant arm, according to a 0, 1, 6-month schedule in the current study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
HPV vaccine
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Reporting group description |
Healthy female subjects aged 26 years and above, who received control vaccine in the primary study NCT00294047, were administrated 3 intramuscular injections of Cervarix vaccine into the deltoid of the non-dominant arm, according to a 0, 1, 6-month schedule in the current study. | ||
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End point title |
Number of subjects reporting serious adverse events [1] | ||||||||||||
End point description |
Serious adverse events (SAEs) assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as the occurrence of any SAE regardless of intensity grade or relation to vaccination. Grade 3 SAE = SAE which prevented normal, everyday activities (in adults/adolescents, such an SAE, for example, prevented attendance at work/school and necessitated the administration of corrective therapy). Related SAE = SAE assessed by the investigator as causally related to the vaccination.
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End point type |
Primary
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End point timeframe |
Throughout the study (from Month 0 to Month 12)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The scope of this primary end point was descriptive, no statistical hypothesis test was performed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of subjects reporting medically significant conditions (MSCs) and potential immune-mediated diseases (pIMDs) [2] | ||||||||||||||||||
End point description |
Medically significant conditions (MSCs) are defined as: AEs prompting emergency room or physician visits that were not related to common diseases, or not related to routine visits for physical examination or vaccination; SAEs that were not related to common diseases. Common diseases include: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury. Potential immune-mediated diseases (pIMDs) are a subset of medically significant conditions that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. Any was defined as the occurrence of any MSC or pIMD regardless of intensity grade or relation to vaccination. Grade 3 MSC or pIMD = a MSC or pIMD which prevented normal, everyday activities. Related MSC or pIMD = a MSC or pIMD assessed by the investigator as related to the vaccination.
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End point type |
Primary
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End point timeframe |
Throughout the study (from Month 0 to Month 12)
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The scope of this primary end point was descriptive, no statistical hypothesis test was performed. |
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End point title |
Number of subjects reporting pregnancies and outcome of reported pregnancies [3] | ||||||||||||||||||||||||||||||||||||
End point description |
Live infant NO apparent congenital anomaly; Live infant congenital anomaly; Premature live infant NO apparent congenital anomaly; Premature live infant congenital anomaly; Elective termination NO apparent congenital anomaly; Elective termination congenital anomaly; Therapeutic abortion; Ectopic pregnancy; Spontaneous abortion NO apparent congenital anomaly; Spontaneous abortion congenital anomaly; Stillbirth NO apparent congenital anomaly; Stillbirth congenital anomaly; Molar pregnancy; Pregnancy ongoing; Lost to follow up.
The analysis was based on the Total Vaccinated cohort, which included all subjects with the study vaccine administered and who reported any pregnancies and outcomes of reported pregnancies.
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End point type |
Primary
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End point timeframe |
Throughout the study (from Month 0 to Month 12)
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The scope of this primary end point was descriptive, no statistical hypothesis test was performed. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
Adverse Events were reported from the first receipt of study vaccine (Month 0) until 6 months following administration of the last dose of study vaccine (i.e. at study conclusion, Month 12).
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Adverse event reporting additional description |
Non-serious solicited adverse events were not collected in this study. Non-serious unsolicited events collected in this study did not exceed the threshold of 5%.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
HPV vaccine
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Reporting group description |
Healthy female subjects aged 26 years and above, who received control vaccine in the primary study NCT00294047, were administrated 3 intramuscular injections of Cervarix vaccine into the deltoid of the non-dominant arm, according to a 0, 1, 6-month schedule in the current study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Non-serious solicited adverse events were not collected in this study. Non-serious unsolicited adverse events collected included MSCs and pIMDs, presented previously as a primary endpoint. |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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09 Dec 2010 |
Due to their potent immune stimulating effect, there are theoretical concerns that modern adjuvants like GSK Biologicals' novel adjuvant systems might result in undesirable effects on the body's immune system, which could include onset of new or exacerbation of underlying autoimmune diseases in particular. Accordingly, a heightened surveillance on the occurrence of any such conditions in recipients of novel adjuvant containing vaccines in clinical trials has been put in place by GSK. Protocol amendment 1 was hence developed to implement reporting of potential immune-mediated diseases (pIMDs). |
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13 Jan 2011 |
"The exclusion criterion “Administration of any chronic drug therapy to be continued during the study period” has been removed to be in line with the original HPV-015 study protocol.
Upon request of regulatory authorities, the list of pIMDs has been updated to include the term “undifferentiated spondyloarthritides”." |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
