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Completed

NCT Number: NCT01031069

Evaluation of Safety and Immunogenicity of a Human Papillomavirus (HPV) Vaccine in Human Immunodeficiency Virus (HIV) 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).

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Key information

Conditions

Infections, Papillomavirus Communicable Diseases DNA Virus Infections Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Infections Neoplasms Neoplasms by Site Papillomavirus Infections Papillomavirus Vaccines Pathologic Processes Pathological Conditions, Signs and Symptoms Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Tumor Virus Infections Urogenital Diseases Urogenital Neoplasms Uterine Cervical Diseases Uterine Cervical Neoplasms Uterine Diseases Uterine Neoplasms Virus Diseases

Age range

15 year–25 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Primary location

GSK Investigational Site, Porto Alegre, Rio Grande do Sul, Brazil

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.
  • 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.

Exclusion criteria

  • 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.
  • 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.

Treatment and study plan

GSK Biologicals' HPV vaccine 580299

Biological

Subjects received three doses of the study vaccine administered intramuscularly according to a Day 0, Week 6, and Month 6 vaccination schedule.

Other names: Cervarix

Merck's Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine (Gardasil)

Biological

Subjects received three doses of the study vaccine administered intramuscularly according to a Day 0, Week 6, and Month 6 vaccination schedule.

Other names: Gardasil

Primary outcomes

  1. 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).

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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].

  12. 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).

  13. 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).

Secondary outcomes

  1. 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

    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).

  2. 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.

  3. 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

    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.

  4. 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.

  5. 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.

  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)

    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.

  7. Number of Subjects Reporting Pregnancies and Outcomes of Reported Pregnancies

    Time frame: During the entire study period (from Day 0 up to Month 24)

    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.

  8. 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

    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.

  9. 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

    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.

  10. 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

    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.

  11. Number of Subjects With SAEs

    Time frame: During the entire study period (from Day 0 up to Month 24)

    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.

  12. 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)

    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.

  13. 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)

    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.

  14. Cluster of Differentiation 4 (CD4+) Cell Count in HIV+ Subjects at Months 12, 18 and 24

    Time frame: At Months 12, 18 and 24

    CD4+ cell count, expressed in cells/cubic millimeter (mm3), was assessed for HIV+ subjects.

  15. HIV Viral Load (VL) in HIV+ Subjects at Months 12, 18 and 24

    Time frame: At Months 12, 18 and 24

    HIV VL, expressed in HIV copies/milliliter (mL), was assessed for HIV+ subjects.

  16. Number of HIV+ Subjects by WHO HIV Clinical Staging

    Time frame: At Months 12, 18 and 24

    HIV+ subjects were categorised into clinical stages 1 through 4, as per the WHO classification [WHO, 2009].

  17. 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)

    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).

  18. 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 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.

  19. 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

    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.

  20. Frequency of Specific B-cells for HPV-16/18 Antigens

    Time frame: At Day 0, Week 6, Week 10, Month 7 and Month 12

    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-).

  21. 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

    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-).

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Official study title

Safety and Immunogenicity of Cervarix™ in Human Immunodeficiency Virus Infected Females

Important dates

Study start
2010
Primary completion
2016
Study completion
2017
First posted
Dec 14, 2009
Registry last updated
Jul 21, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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