Infections, PapillomavirusPhase 4NCT01031069
Evaluation of Safety and Immunogenicity of a Human Papillomavirus (HPV) Vaccine in Human Immunodeficiency Virus (HIV) Infected Females
A Phase 4 study testing GSK Biologicals' HPV vaccine 580299 and Merck's Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine (Gardasil) in people with Infections, Papillomavirus and Papillomavirus Vaccines, run by GlaxoSmithKline at 15 sites in 4 countries.
Trial summary
Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. This Phase IV, observer-blind study is designed to evaluate the safety and immunogenicity of Cervarix in HIV infected females aged 15 to 25 years as compared to Merck's HPV vaccine (Gardasil). Read more about this study
- Who is it for?
- Ages 15 to 25 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Infections, Papillomavirus, Papillomavirus Vaccines
- What is being tested?
- GSK Biologicals' HPV vaccine 580299 and Merck's Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine (Gardasil)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 873 participants
- Where
- 15 sitesin 4 countries
- Study dates
- 26 Oct 2010to 19 Apr 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 25 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Subjects who the investigator believes that they and/or their parent(s)/legally acceptable representative(s) (LAR) can and will comply with the requirements of the protocol.
- A female between, and including, 15 and 25 years of age at the time of the first vaccination.
- Written informed consent obtained from the subject and/or from the subject's parent or LAR.
- Subjects willing to undergo HIV Voluntary Counseling and Testing (VCT) and willing to be informed of their HIV infection status.
- For HIV seropositive subjects:
- Subjects must be HIV seropositive according to World Health Organization (WHO) case definition.
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- Subject must be asymptomatic (or only have persistent generalized lymphadenopathy).
- Subjects should have a CD4 cell count > 350 cells/mm3.
- If currently taking antiretrovirals (ARVs), subjects must be on compliant to triple therapy (highly active ART) and have undetectable viral load on two previous clinical visits within the six months prior to study entry.
- For HIV seronegative subjects:
- Subjects confirmed as HIV seronegative at the screening visit.
- For non-virgin female subjects:
- Subjects must have no history of abnormal cytology or CIN 1/2/3.
- Subjects must have had no more than six life-time sexual partners prior to enrollment.
- Subjects must have no history of congenital malformations of the uterine cervix, or history of cauterization or surgical procedures involving damage to the transformation zone of the cervix or stenosis.
- Female subjects of non-childbearing potential may be enrolled in the study.
- Female subjects of childbearing potential may be enrolled in the study, if the subject:
- has practiced adequate contraception for 30 days prior to vaccination, and
- has a negative pregnancy test at screening and on the day of vaccination, and
- has agreed to continue adequate contraception during the entire treatment period and for two months after completion of the vaccination series.
Who cannot join
- Previous vaccination against HPV, or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period (Day 0 to Month 24).
- ART not compliant with the National Guidelines.
- Active tuberculosis (TB) visit (criteria mandatory only for HIV+ subjects).
- Current TB therapy.
- Hemoglobin < 8.0 g/dL at the screening visit.
- Creatinine > 1.5-fold the upper limit of normal (ULN) at the screening visit.
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- Alanine aminotransferase (ALT) > 2.5-fold ULN at the screening visit.
- Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period (Day 0 to Month 24).
- Chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs (with the exception of ART) within six months prior to the first vaccine dose.
- Administration of a vaccine not foreseen by the study protocol within 30 days (Days 0 - 29) before the first dose of study vaccine/control. Enrollment will be postponed until the subject is outside the specified window.
- Planned administration of a vaccine not foreseen by the study protocol within 30 days before or 30 days after (i.e., Days 0 - 29) any dose of study vaccine.
- Previous administration of components of the investigational vaccine.
- Cancer or autoimmune disease under treatment.
- Hypersensitivity to latex.
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccine/control.
- Acute disease and/or fever at the time of enrollment.
- Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory testing performed at the screening visit.
- History of any neurological disorders or seizures.
- Pregnant or breastfeeding female.
- A subject planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the study period, up to two months after the last vaccine dose (i.e., up to Month 8).
- Concurrently participating in another clinical study, at any time during the study period (Day 0 to Month 24), in which the subject has been or will be exposed to an investigational or a non-investigational product.
- Any medically diagnosed or suspected immunodeficient condition (other than HIV for HIV seropositive subjects), based on medical history, physical examination and/or laboratory tests results.
- Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine/control or planned administration during the study period. Enrollment will be postponed until the subject is outside the specified window.
- Administration of trimethoprim/sulphamethoxazole within seven days before the first dose of study vaccine/control, or planned administration of trimethoprim/sulphamethoxazole within seven days after the first dose of study vaccine/control.
- Current drugs or alcohol abuse.
- Child in care.
Trial locations and contacts
15 sites in 4 countries.
15 sites in 4 countries
Brazil5 sites
GSK Investigational Site
Campinas, 13083-970
GSK Investigational Site
Porto Alegre, Rio Grande do Sul, 90035003
GSK Investigational Site
Ribeirão Preto, São Paulo, 14049-900
GSK Investigational Site
Rio de Janeiro, 21040-360
GSK Investigational Site
São Paulo, 03015000
India4 sites
GSK Investigational Site
Chennai, 600113
GSK Investigational Site
Kolkata, 700026
GSK Investigational Site
Mumbai, 400014
GSK Investigational Site
Pune, 411001
Thailand4 sites
GSK Investigational Site
Bangkok, 10330
GSK Investigational Site
Bangkok, 10400
GSK Investigational Site
Chiang Mai, 50200
GSK Investigational Site
Khon Kaen, 40002
Estonia2 sites
GSK Investigational Site
Kohtla-Järve, 30322
GSK Investigational Site
Tallinn, 10617
About this study
Official title: Safety and Immunogenicity of Cervarix™ in Human Immunodeficiency Virus Infected Females
Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. This Phase IV, observer-blind study is designed to evaluate the safety and immunogenicity of Cervarix in HIV infected females aged 15 to 25 years as compared to Merck's HPV vaccine (Gardasil). For comparative purposes, a group of HIV negative females will also be evaluated. All subjects will receive the HPV vaccine (either Cervarix or Gardasil) according to a three-dose schedule (Day 0, Week 6, Month 6).
- Being tested
- GSK Biologicals' HPV vaccine 580299, Merck's Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine (Gardasil)
- Keywords
- Cervarix, Gardasil, Immunogenicity, Cervical cancer, Safety, HPV vaccine
- Medical subject headings
- Papillomavirus Infections, Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK Biologicals' HPV vaccine 580299Biological
Also called Cervarix
Subjects received three doses of the study vaccine administered intramuscularly according to a Day 0, Week 6, and Month 6 vaccination schedule.
Merck's Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine (Gardasil)Biological
Also called Gardasil
Subjects received three doses of the study vaccine administered intramuscularly according to a Day 0, Week 6, and Month 6 vaccination schedule.
| Study group | Role | What they receive |
|---|---|---|
| HIV+/Cervarix Group | Experimental | HIV seropositive female subjects, between and including 15 and 25 years of age, who received 3 doses of Cervarix vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6. Receives: Biological: GSK Biologicals' HPV vaccine 580299 |
| HIV+/Gardasil Group | Active comparator | HIV seropositive female subjects, between and including 15 and 25 years of age, who received 3 doses of Gardasil vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6. Receives: Biological: Merck's Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine (Gardasil) |
| HIV-/Cervarix Group | Experimental | HIV seronegative female subjects, between and including 15 and 25 years of age, who received 3 doses of Cervarix vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6. Receives: Biological: GSK Biologicals' HPV vaccine 580299 |
| HIV-/Gardasil Group | Active comparator | HIV seronegative female subjects, between and including 15 and 25 years of age, who received 3 doses of Gardasil vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6. Receives: Biological: Merck's Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine (Gardasil) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Human Immunodeficiency Virus Positive Subjects (HIV+) With Any and Grade 3 Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness, swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest, pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling with a maximum diameter greater than 50 millimeters (mm).
Measured: During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
Number of HIV+ Subjects With Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal [nausea, vomiting, diarrhoea and/or abdominal pain], headache, myalgia, rash, temperature [defined as axillary temperature higher than (>) 37.5 degrees Celsius (°C)] and urticaria. Any = occurrence of the symptom regardless of intensity grade and relationship. Grade 3 symptom = symptom that prevented normal activity. Grade 3 temperature = temperature > 39.0 °C. Grade 3 urticaria = urticaria distributed on at least 4 body areas. Related = symptom assessed by the investigator as related to the vaccination.
Measured: During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
Number of HIV+ 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 symptom = symptom that prevented normal activity. Related = symptom assessed by the investigator as related to the vaccination.
Measured: During the 30-day follow-up period (from the day of vaccination up to 29 subsequent days) after any vaccination
Number of HIV+ Subjects With Serious Adverse Events (SAEs)
SAEs assessed include any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or represented a congenital anomaly/birth defect in the offspring of a study subject.
Measured: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
Number of HIV+ Subjects With Medically Significant Conditions (MSCs)
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.
Measured: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
Number of HIV+ Subjects With Potential Immune-mediated Diseases (pIMDs)
Potential immune-mediated diseases are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
Measured: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
Number of HIV+ Subjects Reporting Pregnancies and Outcomes of Reported Pregnancies
Pregnancy related outcomes were: live infant no apparent congenital anomaly, live infant congenital anomaly, elective termination (termin.) no apparent congenital anomaly, elective termination (termin.) congenital anomaly, ectopic pregnancy, spontaneous abortion no apparent congenital (congen.) anomaly, stillbirth no apparent congenital anomaly, stillbirth congenital anomaly, lost to follow-up, pregnancy ongoing, missing.
Measured: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
Number of HIV+ Subjects With Haematological and Biochemical Parameter Abnormalities
Among assessed haematological and biochemical parameters were: alanine aminotransferase [ALAT], basophilis [BSPH], creatinine [CRT], eosinophils [ESPH], haematocrit [HTCR], haemoglobin [HGB], lymphocytes [LYMP], monocytes [MONO], neutrophils [NTPH], platelets [PLAT], red blood cells [RBC] and white blood cells [WBC]. Unknown = value unknown for the specified visit and laboratory parameter; Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
Measured: At Month 7 (30 days after the last vaccination dose at Month 6)
Cluster of Differentiation 4 (CD4+) Cell Count in HIV+ Subjects at Month 7
CD4+ cell count, expressed in cells/cubic millimeter (mm3), was assessed for HIV+ subjects.
Measured: At Month 7 (30 days after the last vaccination dose at Month 6)
HIV Viral Load (VL) in HIV+ Subjects at Month 7
HIV VL, expressed in HIV copies/milliliter (mL), was assessed for HIV+ subjects.
Measured: At Month 7 (30 days after the last vaccination dose at Month 6)
Number of HIV+ Subjects by World Health Organization (WHO) HIV Clinical Staging
HIV+ subjects were categorised into clinical stages 1 through 4, as per the WHO classification [WHO, 2009].
Measured: At Month 7 (30 days after the last vaccination dose at Month 6)
Pseudovirion-Based Neutralization Assay (PBNA) Titers of Anti-HPV-16/18 Antibodies in HIV+ Subjects, Based on Adapted According-to-protocol (ATP) Cohort for Immunogenicity
Titers of anti-HPV-16/18 antibodies, expressed as Geometric Mean Titers (GMTs), with cut-offs greater than or equal to (≥) 40 estimated dose giving 50% signal reduction when compared to a control without serum (ED50), as assessed by the Pseudovirion-Based Neutralization Assay [PBNA], in HIV+ subjects.
Between-group comparisons to assess non-inferiority were performed on the ATP cohort for immunogenicity (by PBNA, regardless of HPV serostatus at baseline).
Measured: At Month 7 (30 days after the last vaccination dose at Month 6)
Pseudovirion-Based Neutralization Assay (PBNA) Titers of Anti-HPV-16/18 Antibodies in HIV+ Subjects, Based on Total Vaccinated Cohort (TVC)
Titers of anti-HPV-16/18 antibodies, expressed as Geometric Mean Titers (GMTs), with cut-offs greater than or equal to (≥) 40 estimated dose giving 50% signal reduction when compared to a control without serum (ED50), as assessed by the Pseudovirion-Based Neutralization Assay [PBNA], in HIV+ subjects.
Between-group comparisons to assess superiority were performed on the TVC (by PBNA, regardless of HPV serostatus at baseline).
Measured: At Month 7 (30 days after the last vaccination dose at Month 6)
Secondary outcomes (21)
Number of HIV- Subjects With Any and Grade 3 Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness, swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest, pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling with a maximum diameter greater than 50 millimeters (mm).
Measured: During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
Number of HIV- Subjects With Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal [nausea, vomiting, diarrhoea and/or abdominal pain], headache, myalgia, rash, temperature [defined as axillary temperature higher than (>) 37.5 degrees Celsius (°C)] and urticaria. Any = occurrence of the symptom regardless of intensity grade and relationship. Grade 3 symptom = symptom that prevented normal activity. Grade 3 temperature = temperature > 39.0 °C. Grade 3 urticaria = urticaria distributed on at least 4 body areas. Related = symptom assessed by the investigator as related to the vaccination.
Measured: During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
Number of HIV- Subjects With 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 symptom = symptom that prevented normal activity. Related = symptom assessed by the investigator as related to the vaccination.
Measured: During the 30-day follow-up period (from the day of vaccination up to 29 subsequent days) after any vaccination
Number of HIV- Subjects With Serious Adverse Events (SAEs)
SAEs assessed include any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or represented a congenital anomaly/birth defect in the offspring of a study subject.
Measured: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
Number of HIV- Subjects With Medically Significant Conditions (MSCs)
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.
Measured: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
Number of HIV- Subjects With Potential Immune-mediated Disease (pIMDs)
Potential immune-mediated diseases are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
Measured: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
Number of Subjects Reporting Pregnancies and Outcomes of Reported Pregnancies
Pregnancy related outcomes were: live infant no apparent congenital anomaly, live infant congenital anomaly, elective termination (termin.) no apparent congenital anomaly, elective termination (termin.) congenital anomaly, ectopic pregnancy, spontaneous abortion no apparent congenital (congen.) anomaly, stillbirth no apparent congenital anomaly, stillbirth congenital anomaly, lost to follow-up, pregnancy ongoing, missing.
Measured: During the entire study period (from Day 0 up to Month 24)
Number of Subjects With Relevant Abnormalities in Alanine Aminotransferase, Basophils, Creatinine and Eosinophils Parameters
Among assessed haematological and biochemical parameters were: alanine aminotransferase [ALAT], basophils [BSPH], creatinine [CRT], eosinophils [ESPH]. Unknown = value unknown for the specified visit and laboratory parameter; Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
Measured: At Day 0, Week 6, Week 10, Month 6, Month 7, Month 12, Month 18 and Month 24
Number of Subjects With Relevant Abnormalities in Haematocrit, Haemoglobin, Lymphocytes and Monocytes Parameters
Among assessed haematological parameters were: haematocrit [HTCR], haemoglobin [HGB], lymphocytes [LYMP] and monocytes [MONO]. Unknown = value unknown for the specified visit and laboratory parameter; Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
Measured: At Day 0, Week 6, Week 10, Month 6, Month 7, Month 12, Month 18 and Month 24
Number of Subjects With Relevant Abnormalities in Neutrophils, Platelets, Red Blood Cells and White Blood Cells Parameters
Among assessed haematological parameters were: neutrophils [NTPH], platelets [PLAT], red blood cells [RBC] and white blood cells [WBC]. Unknown = value unknown for the specified visit and laboratory parameter; Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
Measured: At Day 0, Week 6, Week 10, Month 6, Month 7, Month 12, Month 18 and Month 24
Number of Subjects With SAEs
SAEs assessed include any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or represented a congenital anomaly/birth defect in the offspring of a study subject.
Measured: During the entire study period (from Day 0 up to Month 24)
Number of Subjects With Medically Significant Conditions (MSCs)
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.
Measured: From Day 0 up to Month 18 (from Day 0 up to 12 months after the last vaccination dose at Month 6)
Number of Subjects With Potential Immune-mediated Diseases (pIMDs)
Potential immune-mediated diseases are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
Measured: From Day 0 up to Month 18 (from Day 0 up to 12 months after the last vaccination dose at Month 6)
Cluster of Differentiation 4 (CD4+) Cell Count in HIV+ Subjects at Months 12, 18 and 24
CD4+ cell count, expressed in cells/cubic millimeter (mm3), was assessed for HIV+ subjects.
Measured: At Months 12, 18 and 24
HIV Viral Load (VL) in HIV+ Subjects at Months 12, 18 and 24
HIV VL, expressed in HIV copies/milliliter (mL), was assessed for HIV+ subjects.
Measured: At Months 12, 18 and 24
Number of HIV+ Subjects by WHO HIV Clinical Staging
HIV+ subjects were categorised into clinical stages 1 through 4, as per the WHO classification [WHO, 2009].
Measured: At Months 12, 18 and 24
Pseudovirion-Based Neutralization Assay (PBNA) Titers of Anti-HPV-16/18 Antibodies in HIV- Subjects, Based on TVC
Titers of anti-HPV-16/18 antibodies, expressed as Geometric Mean Titers (GMTs), with cut-offs greater than or equal to (≥) 40 estimated dose giving 50% signal reduction when compared to a control without serum (ED50), as assessed by the Pseudovirion-Based Neutralization Assay [PBNA], for HIV- subjects.
Between-group comparisons to assess superiority were performed on the TVC (by PBNA, regardless of HPV serostatus at baseline).
Measured: At Month 7 (30 days after the last vaccination dose at Month 6)
Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations by Enzyme-linked Immunosorbent Assay (ELISA) in Serum
Anti-HPV-16 and anti-HPV-18 antibody concentrations in serum, are presented as Geometric Mean Concentrations (GMCs), with cut-offs greater than or equal to (≥) 19 ELISA units per milliliter (EU/mL) and 18 EU/mL respectively, as assessed by Enzyme-linked immunosorbent assay (ELISA), in all (HIV+ and HIV-) subjects.
Measured: At Day 0, Week 6, Week 10, Month 7, Month 12, Month 18 and Month 24
Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations by ELISA in Cervicovaginal Secretion (CVS)
Anti-HPV-16 and anti-HPV-18 antibody concentrations in CVS, are presented as Geometric Mean Concentrations (GMCs), with cut-offs greater than or equal to (≥) 0 EU/mL, as assessed by ELISA, in post-menarcheal subjects who volunteered for this procedure.
Measured: At Day 0, Week 6, Week 10, Month 7, Month 12, Month 18 and Month 24
Frequency of Specific B-cells for HPV-16/18 Antigens
B-cell memory was assessed by Enzyme Linked Immuno Spot (ELISPOT) assay. The assay was performed in a subset of approximately 100 subjects (50 HIV+ and 50 HIV-).
Measured: At Day 0, Week 6, Week 10, Month 7 and Month 12
Frequency of Cluster of Differentiation 4/8 [CD4+/CD8+] T-cell Response
The combinations of cytokines expressed were CD4/8-all doubles, CD4/8-d-cluster of differentiation 40 Ligand (CD40L), CD4/8-d-interferon gamma (IFNG), CD4/8-interleukin-2 (IL-2), CD4/8-d-tumour necrosis alpha (TNFA), as assessed by Intracellular cytokine staining (ICS). The assay was performed in a subset of approximately 100 subjects (50 HIV+ and 50 HIV-).
Measured: At Day 0, Week 6, Week 10, Month 7 and Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2009 (estimated)
- Study start26 Oct 2010
- Primary completion13 Jan 2016
- Study completion19 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Infections, PapillomavirusStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 873 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01031069
- Sponsor's protocol ID
- 109823
- Other IDs
- 2013-003429-28
- Status last verified
- Jul 2020
- First submitted
- 10 Dec 2009
- Last updated
- 21 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
Folschweiller N, Teixeira J, Joshi S, Goldani LZ, Supparatpinyo K, Basu P, Chotpitayasunondh T, Chetchotisakd P, Ruxrungtham K, Roteli-Martins C, Grinsztejn B, Quintana SM, Kumarasamy N, Poongulali S, Kulkarni V, Lin L, Datta SK, Descamps D, Dodet M, Dubin G, Friel D, Hezareh M, Karkada N, Meric Camilleri D, Poncelet S, Salaun B, Tavares-da-Silva F, Thomas-Jooris F, Struyf F. Immunogenicity and safety of the AS04-HPV-16/18 and HPV-6/11/16/18 human papillomavirus vaccines in asymptomatic young women living with HIV aged 15-25 years: A phase IV randomized comparative study. EClinicalMedicine. 2020 May 25;23:100353. doi: 10.1016/j.eclinm.2020.100353. eCollection 2020 Jun.
PubMed 32639485
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Immunogenicity of Cervarix™ in Human Immunodeficiency Virus Infected Females
- ClinicalTrials.gov ID
- NCT01031069
- Acronym / sponsor ID
- 109823
- Keywords
- Cervarix, Gardasil, Immunogenicity, Cervical cancer, Safety, HPV vaccine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 873 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 26 Oct 2010 (actual)
- Primary completion
- 13 Jan 2016 (actual)
- Study completion
- 19 Apr 2017 (actual)
- First posted
- 14 Dec 2009 (estimated)
- Results
- Posted 24 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. This Phase IV, observer-blind study is designed to evaluate the safety and immunogenicity of Cervarix in HIV infected females aged 15 to 25 years as compared to Merck's HPV vaccine (Gardasil). For comparative purposes, a group of HIV negative females will also be evaluated. All subjects will receive the HPV vaccine (either Cervarix or Gardasil) according to a three-dose schedule (Day 0, Week 6, Month 6).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| HIV+/Cervarix Group | Experimental | Biological: GSK Biologicals' HPV vaccine 580299HIV seropositive female subjects, between and including 15 and 25 years of age, who received 3 doses of Cervarix vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6. |
| HIV+/Gardasil Group | Active comparator | Biological: Merck's Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine (Gardasil)HIV seropositive female subjects, between and including 15 and 25 years of age, who received 3 doses of Gardasil vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6. |
| HIV-/Cervarix Group | Experimental | Biological: GSK Biologicals' HPV vaccine 580299HIV seronegative female subjects, between and including 15 and 25 years of age, who received 3 doses of Cervarix vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6. |
| HIV-/Gardasil Group | Active comparator | Biological: Merck's Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine (Gardasil)HIV seronegative female subjects, between and including 15 and 25 years of age, who received 3 doses of Gardasil vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6. |
Who may qualify
- Ages
- 15 to 25 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (20 listed)
- Subjects who the investigator believes that they and/or their parent(s)/legally acceptable representative(s) (LAR) can and will comply with the requirements of the protocol.
- A female between, and including, 15 and 25 years of age at the time of the first vaccination.
- Written informed consent obtained from the subject and/or from the subject's parent or LAR.
- Subjects willing to undergo HIV Voluntary Counseling and Testing (VCT) and willing to be informed of their HIV infection status.
- For HIV seropositive subjects:
Key exclusion criteria (26 listed)
- Previous vaccination against HPV, or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period (Day 0 to Month 24).
- ART not compliant with the National Guidelines.
- Active tuberculosis (TB) visit (criteria mandatory only for HIV+ subjects).
- Current TB therapy.
- Hemoglobin < 8.0 g/dL at the screening visit.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK Biologicals' HPV vaccine 580299Also: CervarixSubjects received three doses of the study vaccine administered intramuscularly according to a Day 0, Week 6, and Month 6 vaccination schedule. | Biological | HIV+/Cervarix Group, HIV-/Cervarix Group |
| Merck's Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine (Gardasil)Also: GardasilSubjects received three doses of the study vaccine administered intramuscularly according to a Day 0, Week 6, and Month 6 vaccination schedule. | Biological | HIV+/Gardasil Group, HIV-/Gardasil Group |
Primary outcome
Number of Human Immunodeficiency Virus Positive Subjects (HIV+) With Any and Grade 3 Solicited Local Symptoms
Time frame: During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
Assessed solicited local symptoms were pain, redness, swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest, pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling with a maximum diameter greater than 50 millimeters (mm).
Number of HIV+ Subjects With Any, Grade 3 and Related Solicited General Symptoms
Time frame: During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal [nausea, vomiting, diarrhoea and/or abdominal pain], headache, myalgia, rash, temperature [defined as axillary temperature higher than (>) 37.5 degrees Celsius (°C)] and urticaria. Any = occurrence of the symptom regardless of intensity grade and relationship. Grade 3 symptom = symptom that prevented normal activity. Grade 3 temperature = temperature > 39.0 °C. Grade 3 urticaria = urticaria distributed on at least 4 body areas. Related = symptom assessed by the investigator as related to the vaccination.
Number of HIV+ Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
Time frame: During the 30-day follow-up period (from the day of vaccination up to 29 subsequent days) after any vaccination
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 symptom = symptom that prevented normal activity. Related = symptom assessed by the investigator as related to the vaccination.
Number of HIV+ Subjects With Serious Adverse Events (SAEs)
Time frame: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
SAEs assessed include any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or represented a congenital anomaly/birth defect in the offspring of a study subject.
Number of HIV+ Subjects With Medically Significant Conditions (MSCs)
Time frame: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
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.
Number of HIV+ Subjects With Potential Immune-mediated Diseases (pIMDs)
Time frame: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
Potential immune-mediated diseases are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
Number of HIV+ Subjects Reporting Pregnancies and Outcomes of Reported Pregnancies
Time frame: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
Pregnancy related outcomes were: live infant no apparent congenital anomaly, live infant congenital anomaly, elective termination (termin.) no apparent congenital anomaly, elective termination (termin.) congenital anomaly, ectopic pregnancy, spontaneous abortion no apparent congenital (congen.) anomaly, stillbirth no apparent congenital anomaly, stillbirth congenital anomaly, lost to follow-up, pregnancy ongoing, missing.
Number of HIV+ Subjects With Haematological and Biochemical Parameter Abnormalities
Time frame: At Month 7 (30 days after the last vaccination dose at Month 6)
Among assessed haematological and biochemical parameters were: alanine aminotransferase [ALAT], basophilis [BSPH], creatinine [CRT], eosinophils [ESPH], haematocrit [HTCR], haemoglobin [HGB], lymphocytes [LYMP], monocytes [MONO], neutrophils [NTPH], platelets [PLAT], red blood cells [RBC] and white blood cells [WBC]. Unknown = value unknown for the specified visit and laboratory parameter; Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
Cluster of Differentiation 4 (CD4+) Cell Count in HIV+ Subjects at Month 7
Time frame: At Month 7 (30 days after the last vaccination dose at Month 6)
CD4+ cell count, expressed in cells/cubic millimeter (mm3), was assessed for HIV+ subjects.
HIV Viral Load (VL) in HIV+ Subjects at Month 7
Time frame: At Month 7 (30 days after the last vaccination dose at Month 6)
HIV VL, expressed in HIV copies/milliliter (mL), was assessed for HIV+ subjects.
Number of HIV+ Subjects by World Health Organization (WHO) HIV Clinical Staging
Time frame: At Month 7 (30 days after the last vaccination dose at Month 6)
HIV+ subjects were categorised into clinical stages 1 through 4, as per the WHO classification [WHO, 2009].
Pseudovirion-Based Neutralization Assay (PBNA) Titers of Anti-HPV-16/18 Antibodies in HIV+ Subjects, Based on Adapted According-to-protocol (ATP) Cohort for Immunogenicity
Time frame: At Month 7 (30 days after the last vaccination dose at Month 6)
Titers of anti-HPV-16/18 antibodies, expressed as Geometric Mean Titers (GMTs), with cut-offs greater than or equal to (≥) 40 estimated dose giving 50% signal reduction when compared to a control without serum (ED50), as assessed by the Pseudovirion-Based Neutralization Assay [PBNA], in HIV+ subjects. Between-group comparisons to assess non-inferiority were performed on the ATP cohort for immunogenicity (by PBNA, regardless of HPV serostatus at baseline).
Pseudovirion-Based Neutralization Assay (PBNA) Titers of Anti-HPV-16/18 Antibodies in HIV+ Subjects, Based on Total Vaccinated Cohort (TVC)
Time frame: At Month 7 (30 days after the last vaccination dose at Month 6)
Titers of anti-HPV-16/18 antibodies, expressed as Geometric Mean Titers (GMTs), with cut-offs greater than or equal to (≥) 40 estimated dose giving 50% signal reduction when compared to a control without serum (ED50), as assessed by the Pseudovirion-Based Neutralization Assay [PBNA], in HIV+ subjects. Between-group comparisons to assess superiority were performed on the TVC (by PBNA, regardless of HPV serostatus at baseline).
21 secondary outcomes
Number of HIV- Subjects With Any and Grade 3 Solicited Local Symptoms
Time frame: During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
Number of HIV- Subjects With Any, Grade 3 and Related Solicited General Symptoms
Time frame: During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
Number of HIV- Subjects With Unsolicited Adverse Events (AEs)
Time frame: During the 30-day follow-up period (from the day of vaccination up to 29 subsequent days) after any vaccination
Number of HIV- Subjects With Serious Adverse Events (SAEs)
Time frame: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
Number of HIV- Subjects With Medically Significant Conditions (MSCs)
Time frame: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
Number of HIV- Subjects With Potential Immune-mediated Disease (pIMDs)
Time frame: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
Number of Subjects Reporting Pregnancies and Outcomes of Reported Pregnancies
Time frame: During the entire study period (from Day 0 up to Month 24)
Number of Subjects With Relevant Abnormalities in Alanine Aminotransferase, Basophils, Creatinine and Eosinophils Parameters
Time frame: At Day 0, Week 6, Week 10, Month 6, Month 7, Month 12, Month 18 and Month 24
Number of Subjects With Relevant Abnormalities in Haematocrit, Haemoglobin, Lymphocytes and Monocytes Parameters
Time frame: At Day 0, Week 6, Week 10, Month 6, Month 7, Month 12, Month 18 and Month 24
Number of Subjects With Relevant Abnormalities in Neutrophils, Platelets, Red Blood Cells and White Blood Cells Parameters
Time frame: At Day 0, Week 6, Week 10, Month 6, Month 7, Month 12, Month 18 and Month 24
Number of Subjects With SAEs
Time frame: During the entire study period (from Day 0 up to Month 24)
Number of Subjects With Medically Significant Conditions (MSCs)
Time frame: From Day 0 up to Month 18 (from Day 0 up to 12 months after the last vaccination dose at Month 6)
Number of Subjects With Potential Immune-mediated Diseases (pIMDs)
Time frame: From Day 0 up to Month 18 (from Day 0 up to 12 months after the last vaccination dose at Month 6)
Cluster of Differentiation 4 (CD4+) Cell Count in HIV+ Subjects at Months 12, 18 and 24
Time frame: At Months 12, 18 and 24
HIV Viral Load (VL) in HIV+ Subjects at Months 12, 18 and 24
Time frame: At Months 12, 18 and 24
Number of HIV+ Subjects by WHO HIV Clinical Staging
Time frame: At Months 12, 18 and 24
Pseudovirion-Based Neutralization Assay (PBNA) Titers of Anti-HPV-16/18 Antibodies in HIV- Subjects, Based on TVC
Time frame: At Month 7 (30 days after the last vaccination dose at Month 6)
Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations by Enzyme-linked Immunosorbent Assay (ELISA) in Serum
Time frame: At Day 0, Week 6, Week 10, Month 7, Month 12, Month 18 and Month 24
Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations by ELISA in Cervicovaginal Secretion (CVS)
Time frame: At Day 0, Week 6, Week 10, Month 7, Month 12, Month 18 and Month 24
Frequency of Specific B-cells for HPV-16/18 Antigens
Time frame: At Day 0, Week 6, Week 10, Month 7 and Month 12
Frequency of Cluster of Differentiation 4/8 [CD4+/CD8+] T-cell Response
Time frame: At Day 0, Week 6, Week 10, Month 7 and Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32639485Folschweiller N, Teixeira J, Joshi S, Goldani LZ, Supparatpinyo K, Basu P, Chotpitayasunondh T, Chetchotisakd P, Ruxrungtham K, Roteli-Martins C, Grinsztejn B, Quintana SM, Kumarasamy N, Poongulali S, Kulkarni V, Lin L, Datta SK, Descamps D, Dodet M, Dubin G, Friel D, Hezareh M, Karkada N, Meric Camilleri D, Poncelet S, Salaun B, Tavares-da-Silva F, Thomas-Jooris F, Struyf F. Immunogenicity and safety of the AS04-HPV-16/18 and HPV-6/11/16/18 human papillomavirus vaccines in asymptomatic young women living with HIV aged 15-25 years: A phase IV randomized comparative study. EClinicalMedicine. 2020 May 25;23:100353. doi: 10.1016/j.eclinm.2020.100353. eCollection 2020 Jun.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
15 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing GSK Biologicals' HPV vaccine 580299 and Merck's Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine (Gardasil) in people with Infections, Papillomavirus and Papillomavirus Vaccines, run by GlaxoSmithKline at 15 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Brazil, India, Thailand, Estonia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Human Immunodeficiency Virus Positive Subjects (HIV+) With Any and Grade 3 Solicited Local Symptoms (time frame: During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01031069, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2020.