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.

Study Overview

• Status: Not yet recruiting
• Conditions: Human Papillomavirus Infection
• Intervention / Treatment: Biological: Cervavac as three dose regimen; Biological: Cervavac as two dose regimen; Biological: Gardasil as three dose regimen

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Hitt Sharma; Phone Number: +912026602451; Email: drhjs@seruminstitute.com
• Study Contact Backup: Name: Sameer Parekh; Phone Number: +912026602139; Email: sameer.parekh@seruminstitute.com

Study Locations

• Kenya
  • Nairobi, Kenya, 54840-00200
    • Centre For Clinical Research, Kemri
    • Contact: Nelly Mugo; Phone Number: +254733629665; Email: rwamba@uw.edu
  • Thika, Kenya, 19865-00202
    • Partners in Health and Research Development (Phrd)
    • Contact: Nelly Mugo; Phone Number: +254733629665; Email: rwamba@uw.edu
• Mozambique
  • Manhiça, Mozambique, 1929
    • Manhiça Health Research Center - Manhiça Foundation (CISM-FM)
    • Contact: Tacilta Nhampossa; Phone Number: +258 21 810 181; Email: tacilta.nhampossa@manhica.net
• South Africa
  • Johannesburg, South Africa, 2092
    • Clinical HIV Research Unit (CHRU), Helen Joseph Hospital
    • Contact: Carla Chibwesha; Phone Number: +27 072 744 7899; Email: carla_chibwesha@med.unc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cervavac administered as three doses; Recombinant Quadrivalent Human Papillomavirus (Types 6,11 16, 18) Vaccine manufactured by Serum Institute of India Pvt Ltd administered as three doses at day 0, 60 and 180.	Biological: Cervavac as three dose regimen; Cervavac manufactured by Serum Institute of India Pvt Ltd administered as three doses at day 0, 60 and 180.
Experimental: Cervavac administered as two doses; Recombinant Quadrivalent Human Papillomavirus (Types 6,11 16, 18) Vaccine manufactured by Serum Institute of India Pvt Ltd administered as two doses at day 0 and 180.	Biological: Cervavac as two dose regimen; Cervavac manufactured by Serum Institute of India Pvt Ltd administered as two doses at day 0 and 180.
Active Comparator: Gardasil administered as three doses; Recombinant Quadrivalent Human Papillomavirus (Types 6,11 16, 18) Vaccine manufactured by MSD administered as three doses at day 0, 60 and 180.	Biological: Gardasil as three dose regimen; Gardasil manufactured by MSD administered as a three doses at day 0,60 and 180.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric mean titers of anti HPV 16 and 18 IgG antibodies	GMTs of anti HPV 16 and 18 IgG antibodies in WLWH receiving 3 doses of SIIPL qHPV and 3 doses of Gardasil®	at 1 month after the last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune response (Geometric mean titers) of anti HPV 6 and 11 IgG antibodies	Geometric mean titers of anti HPV 6 and 11 IgG antibodies in WLWH receiving 3 doses of SIIPL qHPV or Gardasil	at 1 month after the last dose
Geometric mean titers of anti HPV 6, 11, 16 and 18 IgG antibodies and Pecentage seroconversion	Geometric mean titers of anti HPV 6, 11, 16 and 18 IgG antibodies and Pecentage seroconversion in WLWH receiving 2 doses or 3 doses of SIIPL qHPV or 3 doses of Gardasil	at 1 month after the last dose
Adverse Events	Incidence, severity, and relationship of local and systemic solicited AEs up to 7 days following each vaccination. Incidence, severity, and relationship of unsolicited AEs from Day 0 through Month 7 and Month 12. Incidence, severity, and relationship of SAEs from Day 0 through Month 7 and Month 12.	solicited AEs up to 7 days following each vaccination, unsolicited AEs from Day 0 through Month 7 and Month12 and SAEs from Day 0 through Month 7 and Month 12.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric mean titers of anti HPV 6, 11, 16 and 18 IgG antibodies and Pecentage seroconversion	Immune response to HPV types 6, 11, 16 & 18 in WLWH receiving 2 doses of SIIPL qHPV vaccine, 3 doses of SIIPL qHPV vaccine and 3 doses of Gardasil® vaccine, at Month 12.	at Month 12
Geometric mean titers of anti HPV 6, 11, 16 and 18 IgG antibodies and Pecentage	Immune response to HPV types 6, 11, 16 & 18 after 1st dose	at Month 2 and 6
CD4+ cell count, HIV viral load, and HIV clinical staging	Assessment of CD4+ cell count, HIV viral load, and HIV clinical staging in WLWH	at Month 7 and Month 12

Collaborators and Investigators

• Sponsor: Serum Institute of India Pvt. Ltd.
• Collaborators: Bill and Melinda Gates Foundation
• Investigators: Principal Investigator: Carla Chibwesha, Clinical HIV Research Unit, Helen Joseph Hospital, Johannesburg, South Africa; Principal Investigator: Nelly Mugo, CCR, KEMRI, Nairobi-Kenya & PHRD, Thika-Kenya; Principal Investigator: Tacilta Nhampossa, Manhiça Health Research Center - Manhiça Foundation,Manhiça

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: February 20, 2024
• First Submitted That Met QC Criteria: February 20, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Vaccine; HPV; Quadrivalent; Cervavac
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Disease Attributes; DNA Virus Infections; Tumor Virus Infections; Urogenital Diseases; Genital Diseases; Papillomavirus Infections
• Other Study ID Numbers: SII-qHPV/MC-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Summary results for primary and secondary objectives
• IPD Sharing Time Frame: 12 Months after completion of the study
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal may be provided the access after Sponsor permission and if signed data-access agreements are in place.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No