Clinical trial NCT01031069: Evaluation of Safety and Immunogenicity of a Human Papillomavirus (HPV) Vaccine in Human Immunodeficiency Virus (HIV) Infected Females
Official title: Safety and Immunogenicity of Cervarix™ in Human Immunodeficiency Virus Infected Females
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Infections, Papillomavirus
Papillomavirus Vaccines
Keywords: Cervarix
Gardasil
Immunogenicity
Cervical cancer
Safety
HPV vaccine
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-12-14
Enrollment: 873
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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). 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Human Immunodeficiency Virus Positive Subjects (HIV+) With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
measure: Number of HIV+ Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
measure: Number of HIV+ Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
timeFrame: During the 30-day follow-up period (from the day of vaccination up to 29 subsequent days) after any vaccination
measure: Number of HIV+ Subjects With Serious Adverse Events (SAEs)
timeFrame: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
measure: Number of HIV+ Subjects With Medically Significant Conditions (MSCs)
timeFrame: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
measure: Number of HIV+ Subjects With Potential Immune-mediated Diseases (pIMDs)
timeFrame: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
measure: Number of HIV+ Subjects Reporting Pregnancies and Outcomes of Reported Pregnancies
timeFrame: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
measure: Number of HIV+ Subjects With Haematological and Biochemical Parameter Abnormalities
timeFrame: At Month 7 (30 days after the last vaccination dose at Month 6)
measure: Cluster of Differentiation 4 (CD4+) Cell Count in HIV+ Subjects at Month 7
timeFrame: At Month 7 (30 days after the last vaccination dose at Month 6)
measure: HIV Viral Load (VL) in HIV+ Subjects at Month 7
timeFrame: At Month 7 (30 days after the last vaccination dose at Month 6)
measure: Number of HIV+ Subjects by World Health Organization (WHO) HIV Clinical Staging
timeFrame: At Month 7 (30 days after the last vaccination dose at Month 6)
measure: 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
timeFrame: At Month 7 (30 days after the last vaccination dose at Month 6)
measure: Pseudovirion-Based Neutralization Assay (PBNA) Titers of Anti-HPV-16/18 Antibodies in HIV+ Subjects, Based on Total Vaccinated Cohort (TVC)
timeFrame: At Month 7 (30 days after the last vaccination dose at Month 6)
Secondary outcomes:
measure: Number of HIV- Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
measure: Number of HIV- Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
measure: Number of HIV- Subjects With Unsolicited Adverse Events (AEs)
timeFrame: During the 30-day follow-up period (from the day of vaccination up to 29 subsequent days) after any vaccination
measure: Number of HIV- Subjects With Serious Adverse Events (SAEs)
timeFrame: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
measure: Number of HIV- Subjects With Medically Significant Conditions (MSCs)
timeFrame: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
measure: Number of HIV- Subjects With Potential Immune-mediated Disease (pIMDs)
timeFrame: From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
measure: Number of Subjects Reporting Pregnancies and Outcomes of Reported Pregnancies
timeFrame: During the entire study period (from Day 0 up to Month 24)
measure: Number of Subjects With Relevant Abnormalities in Alanine Aminotransferase, Basophils, Creatinine and Eosinophils Parameters
timeFrame: At Day 0, Week 6, Week 10, Month 6, Month 7, Month 12, Month 18 and Month 24
measure: Number of Subjects With Relevant Abnormalities in Haematocrit, Haemoglobin, Lymphocytes and Monocytes Parameters
timeFrame: At Day 0, Week 6, Week 10, Month 6, Month 7, Month 12, Month 18 and Month 24
measure: Number of Subjects With Relevant Abnormalities in Neutrophils, Platelets, Red Blood Cells and White Blood Cells Parameters
timeFrame: At Day 0, Week 6, Week 10, Month 6, Month 7, Month 12, Month 18 and Month 24
measure: Number of Subjects With SAEs
timeFrame: During the entire study period (from Day 0 up to Month 24)
measure: Number of Subjects With Medically Significant Conditions (MSCs)
timeFrame: From Day 0 up to Month 18 (from Day 0 up to 12 months after the last vaccination dose at Month 6)
measure: Number of Subjects With Potential Immune-mediated Diseases (pIMDs)
timeFrame: From Day 0 up to Month 18 (from Day 0 up to 12 months after the last vaccination dose at Month 6)
measure: Cluster of Differentiation 4 (CD4+) Cell Count in HIV+ Subjects at Months 12, 18 and 24
timeFrame: At Months 12, 18 and 24
measure: HIV Viral Load (VL) in HIV+ Subjects at Months 12, 18 and 24
timeFrame: At Months 12, 18 and 24
measure: Number of HIV+ Subjects by WHO HIV Clinical Staging
timeFrame: At Months 12, 18 and 24
measure: Pseudovirion-Based Neutralization Assay (PBNA) Titers of Anti-HPV-16/18 Antibodies in HIV- Subjects, Based on TVC
timeFrame: At Month 7 (30 days after the last vaccination dose at Month 6)
measure: Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations by Enzyme-linked Immunosorbent Assay (ELISA) in Serum
timeFrame: At Day 0, Week 6, Week 10, Month 7, Month 12, Month 18 and Month 24
measure: Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations by ELISA in Cervicovaginal Secretion (CVS)
timeFrame: At Day 0, Week 6, Week 10, Month 7, Month 12, Month 18 and Month 24
measure: Frequency of Specific B-cells for HPV-16/18 Antigens
timeFrame: At Day 0, Week 6, Week 10, Month 7 and Month 12
measure: Frequency of Cluster of Differentiation 4/8 [CD4+/CD8+] T-cell Response
timeFrame: At Day 0, Week 6, Week 10, Month 7 and Month 12
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
state: Rio Grande Do Sul
city: Ribeirão Preto
country: Brazil
facility: GSK Investigational Site
state: São Paulo
city: Campinas
country: Brazil
facility: GSK Investigational Site
city: Rio de Janeiro
country: Brazil
facility: GSK Investigational Site
city: São Paulo
country: Brazil
facility: GSK Investigational Site
city: Kohtla-Järve
country: Estonia
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Chennai
country: India
facility: GSK Investigational Site
city: Kolkata
country: India
facility: GSK Investigational Site
city: Mumbai
country: India
facility: GSK Investigational Site
city: Pune
country: India
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Chiangmai
country: Thailand
facility: GSK Investigational Site
city: Khon Kaen
country: Thailand
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.