Efficacy, Immunogenicity and Safety of V503 in Chinese Women Aged 20-45 Years (V503-023)

NCT03998254 | Active Not Recruiting Phase 3 FDA Drug

• 1 other identifier: V503-023
• Study Type: interventional
• Target: 6,000
• Locations: 1 country
• Sites: 6

Brief Summary

This study will evaluate the efficacy, immunogenicity and safety of 9-valent human papillomavirus (9vHPV; V503) vaccine in Chinese women 20 to 45 years of age. The primary hypotheses are: 9vHPV vaccine reduces the incidence of HPV 31-, 33-, 45-, 52-, and 58-related 12-month persistent infection at least 1 month post Dose 3, compared with quadrivalent HPV (qHPV) vaccine in women 20 to 45 years of age who are seronegative at Day 1 and polymerase chain reaction (PCR) negative Day 1 through Month 7 to the relevant HPV type; and 9vHPV vaccine induces non-inferior competitive luminex immunoassay (cLIA) geometric mean titers (GMTs) for each of HPV 6, 11, 16, and 18 one month post Dose 3, compared with qHPV vaccine in women 20 to 45 years of age who are seronegative at Day 1 and PCR negative Day 1 through Month 7 to the relevant HPV type.

Conditions

Papillomavirus Infections

Outcome Measures

Primary Outcomes (7)

• Stage I: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related 12-month Persistent Infection

  A 12-month persistent infection This endpoint is defined to have occurred if a participant who is positive for the same HPV type by the HPV PCR assay in the LVPP/EEC swabs, biopsy, ECC or definitive therapy samples obtained in 3 or more consecutive visits over a period of at least 12 months. Incidence is defined as the number of cases of persistent infection per 10,000 person-years of follow-up in a treatment arm.

  1 month post vaccination 3 (Month 7) up to Month 30

• Stage I: Geometric Mean Titers to HPV Types 6, 11, 16, and 18 Antibodies

  Serum antibodies to HPV types 6/11/16/18 are measured with a Competitive Luminex Immunoassay (cLIA). Titers are reported in milli Merck Units/mL.

  1-month post vaccination 3 (Month 7)

• Stage I: Percentage of Participants Who Report at Least 1 Solicited Injection-site Adverse Event

  An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. AEs such as redness, swelling, and pain/tenderness/soreness at the injection site are recorded.

  up to 8 days post any vaccination

• Stage I: Percentage of Participants Who Report at Least 1 Solicited Systemic Adverse Event

  An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. Systemic AEs are those not categorized as injection-site AEs.

  up to 30 days post any vaccination

• Stage I: Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE)

  An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. An SAE is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, or is another important medical event.

  Day 1 up to approximately Month 30

• Stage II: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related CIN 2/3, AIS, and cervical cancer

  This endpoint is defined to have occurred if on a single cervical biopsy, ECC, LEEP or Conization (cold knife/laser) specimen, there is: (a) a HPV Pathology Panel consensus diagnosis of CIN (grade 2 or 3), AIS, or cervical cancer; AND (b) detection of at least 1 of HPV types 31, 33, 45, 52 or 58 by Thinsection PCR in an adjacent section from the same tissue block. Disease incidence is defined as the number cases per 10,000 person-years of follow-up in a treatment arm.

  Month 7 up to Month 90

• Stages I/II: Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE)

  An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. An SAE is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, or is another important medical event.

  Day 1 up to approximately Month 90

Secondary Outcomes (13)

• Stage I: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related 6-month Persistent Infection

  1 month post vaccination 3 (Month 7) up to Month 30

• Stage I: Percentage of Participants Who Seroconvert by cLIA to HPV Types 6, 11, 16, and 18

  1 Month Post Vaccination 3 (Month 7)

• Stage I: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related 12-month Persistent Cervical Infection

  1 month post vaccination 3 (Month 7) up to Month 30

• Stage I: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related 12-month Persistent Non-cervical Infection

  1 month post vaccination 3 (Month 7) up to Month 30

• Stage I: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related 6-month Persistent Cervical Infection

  1 month post vaccination 3 (Month 7) up to Month 30

Study Arms (2)

V503

EXPERIMENTAL

Single 0.5-mL intramuscular injection at Day 1, Month 2, and Month 6

Drug: V503

Gardasil

ACTIVE COMPARATOR

Single 0.5-mL intramuscular injection at Day 1, Month 2, and Month 6

Drug: Gardasil

Interventions

V503 DRUG

9vHPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine

V503

Gardasil DRUG

qHPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine

Gardasil

Eligibility Criteria

• Age: 20 Years - 45 Years
• Gender Eligibility Details: Only females will be enrolled
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy
• Has not had sex with males or has had sex with males and used effective contraception with no failures since the first day of the participant's last menstrual period through Day 1
• Agrees to use effective contraception if has sex with a male partner during study
• Has had sexual intercourse with male partners, and has had 1 to 4 male and/or female sexual partners

You may not qualify if:

• History of a positive test for HPV
• History of an abnormal Pap test result showing ASC-US, atypical squamous cells - cannot exclude HSIL (high grade squamous intraepithelial lesion \[(ASC-H)\], low-grade squamous intraepithelial lesion (LSIL), HSIL), or atypical glandular cells
• History of an abnormal cervical biopsy result showing CIN, adenocarcinoma in situ or cervical cancer
• History of or clinical evidence at the Day 1 gynecologic examination of HPV-related anogenital diseases (e.g., genital warts, VIN, VaIN, AIN, vulvular cancer, vaginal cancer or anal cancer
• Does not have an intact cervix uteri or has more than one cervix uteri
• Is pregnant
• Known allergy to any vaccine component, including aluminum, yeast, or Benzonase™ (nuclease, Nycomed™ \[used to remove residual nucleic acids from this and other vaccines\])
• History of severe allergic reaction (e.g., swelling of the mouth and throat, difficulty breathing, hypotension or shock) that required medical intervention
• Has thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections
• Currently immunocompromised or has been diagnosed as having a congenital or acquired immunodeficiency, human immunodeficiency virus (HIV) infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease, or other autoimmune condition
• Has had a splenectomy
• Is expecting to donate eggs during Day 1 through Month 7 of the study
• Plans to receive during Day 1 through Month 7 of the study, is receiving or has received within 12 months prior to enrollment the following immunosuppressive therapies: radiation therapy, cyclophosphamide, azathioprine, methotrexate, any chemotherapy, cyclosporin, leflunomide (Arava™), tumor necrosis factor (TNF)-α antagonists, monocolonal antibody therapies (including rituximab \[Rituxan™\]), intravenous gamma globulin (IVIG), antilymphocyte sera, or other therapy known to interfere with the immune response. With regard to systemic corticosteroids, a participant will be excluded if she is currently receiving steroid therapy, has recently (defined as within 2 weeks of enrollment) received such therapy, or has received 2 or more courses of high dose corticosteroids (orally or parenterally) lasting at least 1 week within 12 months prior to enrollment. Participants using inhaled, nasal, or topical corticosteroids are considered eligible for the study.
• Plans to receive during Day 1 through Month 7 of the study, is receiving or has received within the 6 months prior to the Day 1 vaccination any immune globulin product (including RhoGAM™) or blood derived product other than IVIG
• Has received a marketed HPV vaccine, or has participated in an HPV vaccine clinical study and has received either active agent or placebo

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (6)

Lingchuan Center for Disease Control and Prevention ( Site 0002)

Guilin, Guangxi, 541200, China

Location

Quanzhou Center for Disease Control and Prevention ( Site 0001)

Guilin, Guangxi, 541500, China

Location

Xiangyuan Center for Disease Control and Prevention ( Site 0003)

Changzhi, Shanxi, 046299, China

Location

Yanhu Center for Disease Control and Prevention of Yuncheng ( Site 0004)

Yuncheng, Shanxi, 044000, China

Location

Mianyang Center for Disease Control and Prevention ( Site 0005)

Mianyang, Sichuan, 621000, China

Location

Santai County Center for Disease Control and Prevention ( Site 0006)

Mianyang, Sichuan, 621100, China

Location

Related Publications (1)

• Bergman H, Henschke N, Arevalo-Rodriguez I, Buckley BS, Crosbie EJ, Davies JC, Dwan K, Golder SP, Loke YK, Probyn K, Petkovic J, Villanueva G, Morrison J. Human papillomavirus (HPV) vaccination for the prevention of cervical cancer and other HPV-related diseases: a network meta-analysis. Cochrane Database Syst Rev. 2025 Nov 24;11(11):CD015364. doi: 10.1002/14651858.CD015364.pub2.

  PMID: 41276263 DERIVED

MeSH Terms

Conditions

Papillomavirus Infections

Interventions

Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18

Condition Hierarchy (Ancestors)

Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vaccines, Combined; Vaccines; Biological Products; Complex Mixtures; Papillomavirus Vaccines; Viral Vaccines

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2019
• First Posted: June 26, 2019
• Study Start: June 26, 2019
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2028
• Last Updated: November 16, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share

Locations

CN (6)