Clinical Study to Evaluate SIIPL qHPV Vaccine (CERVAVAC®) in Women Living With HIV Aged 15-25 Years

A Phase-3b, Partially Double-blind, Randomized, Multi-country Clinical Study to Evaluate the Immunogenicity,Safety, and Reactogenicity of SIIPL qHPV Vaccine (CERVAVAC®) in Women Living With HIV Aged 15-25 Years

Human papillomavirus (HPV) infection is the most common viral infection of the reproductive tract. Up to 80%of the sexually active females and men will be infected with HPV at some point in their lives and some may be repeatedly infected. The main burden of HPV-related disease is due to cervical cancer. Since cervical screening only detects precancerous and cancerous changes after they have occurred, HPV vaccination is primary prevention. People with HIV infection, even when effectively treated with antiretroviral therapy (ARV),are at higher risk of acquiring infection with multiple HPV types and are also known to be predisposed to a higher risk of HPV infection and subsequent CIN lesions. Vaccination of this high-risk group with HPV vaccine is highly beneficial. SIIPL's qHPV vaccine CERVAVAC®, India's first indigenous qHPV vaccine has received marketing authorization in India. The current study is a Phase 3b study to evaluate the immunogenicity and safety of two- and three-dose schedules of SIIPL qHPV vaccine in women living with HIV (WLWH) aged 15-25years.

A Phase-3b, partially double-blind, randomized, multi-country study to assess the immunogenicity, safety, and reactogenicity of SIIPL qHPV vaccine in WLWH aged 15-25 years. A total of 450 subjects will be enrolled in the study such that 150 subjects in each group receive either 3-doses of SIIPL qHPV vaccine, 2-doses of SIIPL qHPV vaccine or 3-doses of Gardasil®.

Subjects will be randomized in a 1:1:1 ratio to a 2-dose or 3-dose schedule of SIIPL qHPV vaccine or 3-dose schedule of Gardasil®. This study is designed as a partially double-blind, randomized study with a primary objective to compare the immunogenicity of the 3-dose schedule of SIIPL qHPV vaccine versus a 3-dose schedule of Gardasil®. The secondary objectives include comparison in the immune response between WLWH receiving 2-dose schedule of SIIPL qHPV vaccine and a 3-dose schedule of SIIPL qHPV. The immunogenicity data will be collected up to Month 12 and data at 7-month will be considered for analysis of primary immunogenicity endpoints.

Inclusion Criteria:

1. Women Living with HIV aged 15-25 years at the time of screening

2. Subjects with age 18 years and above, should be willing and able to provide written informed consent while for subjects <18*years of age, parents willing to provide written informed consent and subject is willing to sign written assent form for participation prior to initiating any study related procedure.

3. Subject or parent willing to comply with all study requirements.

4. Subjects who are determined by medical history, physical examination and clinical judgment of the Investigator to be eligible for inclusion in the study.

5. Women of childbearing potential (WOCBP) (sexually active/ ≥18 years of age) must meet all the following criteria:

   Have practiced effective contraception (such as any one of the following: oral, transdermal, injectable or implanted contraceptive; condoms; occlusive cap [diaphragm or cervical vault caps]; spermicidal foam/gel/cream, etc.) or have abstained from all activities that could result in pregnancy from the time of screening up to first vaccine administration (Day 0).

   Have a negative Urine Pregnancy Test (UPT) at screening and on the day of vaccination (Day 0).

   Have agreed to continue effective contraception during the entire treatment period and for two months after completion of the vaccination series.

6. Subject must be asymptomatic (or only have persistent generalized lymphadenopathy) regardless of prior clinical stage.

7. If the subjects were currently taking antiretroviral (ARV) therapy, subjects were to be on highly active antiretroviral therapy (HAART), have undetectable viral load reported at least six months prior, and have a CD4+ cell count >350 cells/mm3 at study entry.

8. If the subjects are not on HAART, subjects should have a CD4+ cell count > 350 cells/mm3 at study entry.

Exclusion Criteria:

1. Known history of prior vaccination with HPV vaccine.
2. Concurrently enrolled in clinical studies of investigational agents or studies involving collection of cervical/genital specimens.
3. Current diagnosis or prior history of genital warts or treatment of genital warts.
4. Current diagnosis or history of treatment for cervical pre malignancies or malignancies.
5. Pregnant females.
6. History of any allergic diseases or severe allergic reaction to any agent.
7. Presence of an acute illness and/or fever at the time of vaccination or during the 72 hours prior to the vaccination.
8. Presence of active tuberculosis or currently on TB therapy.
9. Bleeding diathesis or uncontrolled condition associated with prolonged bleeding that would, in the opinion of the Investigator, contraindicate intramuscular injection.
10. History of major congenital defects or illness that requires medical therapy, as determined by medical history or clinical assessment.
11. History of chronic administration of high doses of corticosteroids, cytotoxic agents or radiotherapy or immunoglobulins, immunosuppressants or other immune-modifying drugs in last 3 months or planned at any time during the study.
12. History of receiving a blood transfusion or other blood products in three months prior to screening.
13. History of any major pulmonary, cardiovascular, renal, neurological, metabolic, gastro-intestinal, hepato-biliary, hematological functional abnormality, mental or physical disability, blood dyscrasia or any condition which in the opinion of the investigator might interfere with the evaluation of the study objectives.
14. History of any cancer, organ transplant or any other immune system disease (other than HIV/AIDs).
15. Subject or subject's parent, is or has an immediate family member who is study specific site staff directly involved with this trial.