Partially Blind Study to Evaluate Immunogenicity & Safety of GSK Bio's HPV Vaccine 580299 in Healthy Women Aged 9-25 Yrs

NCT00541970 | Completed Phase 1 Results

• 1 other identifier: 110659
• Study Type: interventional
• Target: 961
• Locations: 2 countries
• Sites: 25

Brief Summary

Human Papillomavirus (HPV) infection has been established as a necessary cause of cervical cancer. GlaxoSmithKline (GSK) Biologicals has developed an HPV vaccine (580299) which targets the 2 most common oncogenic HPV types (HPV-16 and HPV-18), found in approximately 70% of all cervical cancers. In previous trials this vaccine has been found to be efficacious in the prevention of incident and persistent HPV-16/18 infections and associated cytological abnormalities and cervical dysplasia. In this partially-blind study, GSK Biologicals will evaluate the safety and immunogenicity of the HPV vaccine using an alternative schedule and an alternative dosing when administered in healthy young females aged 9 to 25 years, as compared to the standard HPV vaccine. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007. The protocol posting has been updated following a protocol amendment.

Conditions

Infections, Papillomavirus

Keywords

viral infections; Human Papillomavirus (HPV) vaccine; safety; vaccine; immunogenicity; cervical cancer

Outcome Measures

Primary Outcomes (3)

• Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies

  Titers are given as Geometric Mean Titers (GMTs) expressed in Enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).

  One month after vaccination with the last dose of the Cervarix vaccine (Cervarix 1/Placebo Group: Month 3; Other groups: Month 7).

• Number of Subjects With Report of Any, and Grade 3 Solicited Local Symptoms

  Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the solicited local symptom irrespective of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling larger than (\>) 50 millimeters (mm).

  Within 7 days (Day 0-6) after vaccination.

• Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

  Assessed solicited general symptoms were arthralgia, fatigue, fever (defined as axillary temperature equal or above (≥) 37.5 degrees Celsius (°C), gastrointestinal symptoms, which included nausea, vomiting, diarrhoea and/or abdominal pain, headache, myalgia, rash and urticaria. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature ≥ 39 °C. Grade 3 urticaria = urticaria distributed on at least 4 body areas. Related symptom = symptom assessed by the investigator to be causally related to vaccination.

  Within 7 days (Day 0-6) after vaccination.

Secondary Outcomes (33)

• Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies .

  At Month 3, 1 month after the second dose of vaccine or placebo

• Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies

  At Month 7, 1 month after the last dose of vaccine or placebo.

• Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies

  At Month 12, at Month 18, at Month 24, at Month 36, and at Month 48 during the safety follow-up phase.

• Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies

  At Month 7, 1 month after the last dose of vaccine or placebo.

• Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.

  At Month 7 (M7)

Study Arms (4)

Cervarix 1/Placebo Group

EXPERIMENTAL

Subjects received 2 doses of the Cervarix vaccine, formulation 1, at Month 0 and Month 2, and 1 dose of placebo at Month 6. The Cervarix vaccine and placebo were administered intramuscularly into the deltoid of the non-dominant arm.

Biological: Cervarix; Drug: Placebo

Cervarix 1/Placebo/Cervarix 1 Group

EXPERIMENTAL

Subjects received 2 doses of the Cervarix vaccine, formulation 1, at Month 0 and Month 6, and 1 dose of placebo at Month 2. The Cervarix vaccine and placebo were administered intramuscularly into the deltoid of the non-dominant arm.

Biological: Cervarix; Drug: Placebo

Cervarix 2/Placebo/Cervarix 2 Group

EXPERIMENTAL

Subjects received 2 doses of the Cervarix vaccine, formulation 2, at Month 0 and Month 6, and 1 dose of placebo at Month 2. The Cervarix vaccine and placebo were administered intramuscularly into the deltoid of the non-dominant arm.

Biological: Cervarix; Drug: Placebo

Cervarix 2 Group

EXPERIMENTAL

Subjects received 3 doses of the Cervarix vaccine, formulation 2, at Month 0, Month 2 and Month 6. The Cervarix vaccine was administered intramuscularly into the deltoid of the non-dominant arm.

Biological: Cervarix

Interventions

Cervarix BIOLOGICAL

Intramuscular injection, different dosing /schedule

Also known as: GlaxoSmithKline (GSK) Biologicals' Human Papillomavirus (HPV) vaccine 580299

Cervarix 1/Placebo Group; Cervarix 1/Placebo/Cervarix 1 Group; Cervarix 2 Group; Cervarix 2/Placebo/Cervarix 2 Group

Placebo DRUG

Intramuscular injection, different dosing /schedule

Cervarix 1/Placebo Group; Cervarix 1/Placebo/Cervarix 1 Group; Cervarix 2/Placebo/Cervarix 2 Group

Eligibility Criteria

• Age: 9 Years - 25 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subjects who the investigator believes that they and/or their parents can and will comply with the requirements of the protocol should be enrolled in the study.
• A female subject between, and including, 9 and 25 years of age at the time of the first vaccination.
• Written informed consent/assent obtained from the subject prior to enrolment. For subjects above the legal age of consent, written informed consent must be obtained from the subject. For subjects below the legal age of consent, written informed consent from the subject's parents/legally acceptable representative, and written informed assent must be obtained from the subject.
• Healthy subjects as established by medical history and history-oriented clinical examination before entering into the study.
• Subject must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for two months after completion of the vaccination series.

You may not qualify if:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period (up to Month 24).
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
• Concurrently participating in another clinical study, at any time during the study period (up to Month 24), in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
• Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after the first dose of vaccine. Planned administration/administration of routine vaccines, up to 8 days before the first dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window.
• Pregnant or breastfeeding female.
• A woman planning to become pregnant or planning to discontinue contraceptive precautions during the study period, up to two months after the last vaccine dose.
• Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period (up to Month 24).
• Previous administration of components of the investigational vaccine.
• Cancer or autoimmune disease under treatment.
• Any medically diagnosed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Hypersensitivity to latex.
• Acute disease at the time of enrolment.
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory tests.
• Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period (up to Month 24).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (25)

GSK Investigational Site

Edmonton, Alberta, T6G 2C8, Canada

Location

GSK Investigational Site

Langley, British Columbia, V3A 4H9, Canada

Location

GSK Investigational Site

St. John's, Newfoundland and Labrador, A1E 2C2, Canada

Location

GSK Investigational Site

Truro, Nova Scotia, B2N 1L2, Canada

Location

GSK Investigational Site

Québec, Quebec, G1E 7G9, Canada

Location

GSK Investigational Site

Karlsruhe, Baden-Wurttemberg, 76199, Germany

Location

GSK Investigational Site

Kehl, Baden-Wurttemberg, 77694, Germany

Location

GSK Investigational Site

Rheinstetten, Baden-Wurttemberg, 76287, Germany

Location

GSK Investigational Site

Tauberbischofsheim, Baden-Wurttemberg, 97941, Germany

Location

GSK Investigational Site

Munich, Bavaria, 80637, Germany

Location

GSK Investigational Site

Weilheim, Bavaria, 82362, Germany

Location

GSK Investigational Site

Würzburg, Bavaria, 97070, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60439, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30657, Germany

Location

GSK Investigational Site

Wolfenbüttel, Lower Saxony, 38302, Germany

Location

GSK Investigational Site

Trier, Rhineland-Palatinate, 54290, Germany

Location

GSK Investigational Site

Leipzig, Saxony, 04109, Germany

Location

GSK Investigational Site

Flensburg, Schleswig-Holstein, 24937, Germany

Location

GSK Investigational Site

Nordhausen, Thuringia, 99734, Germany

Location

GSK Investigational Site

Berlin, 13086, Germany

Location

GSK Investigational Site

Berlin, 13125, Germany

Location

GSK Investigational Site

Hamburg, 20246, Germany

Location

GSK Investigational Site

Hamburg, 22159, Germany

Location

GSK Investigational Site

Hamburg, 22525, Germany

Location

Related Publications (6)

• Romanowski B, Schwarz TF, Ferguson LM, Peters K, Dionne M, Schulze K, Ramjattan B, Hillemanns P, Catteau G, Dobbelaere K, Schuind A, Descamps D. Immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine administered as a 2-dose schedule compared with the licensed 3-dose schedule: results from a randomized study. Hum Vaccin. 2011 Dec;7(12):1374-86. doi: 10.4161/hv.7.12.18322. Epub 2011 Dec 1.

  PMID: 22048171 BACKGROUND

• 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

• Folschweiller N, Behre U, Dionne M, Durando P, Esposito S, Ferguson L, Ferguson M, Hillemanns P, McNeil SA, Peters K, Ramjattan B, Schwarz TF, Supparatpinyo K, Suryakirian PV, Janssens M, Moris P, Decreux A, Poncelet S, Struyf F. Long-term Cross-reactivity Against Nonvaccine Human Papillomavirus Types 31 and 45 After 2- or 3-Dose Schedules of the AS04-Adjuvanted Human HPV-16/18 Vaccine. J Infect Dis. 2019 May 5;219(11):1799-1803. doi: 10.1093/infdis/jiy743.

  PMID: 30715452 DERIVED

• Romanowski B, Schwarz TF, Ferguson L, Peters K, Dionne M, Behre U, Schulze K, Hillemanns P, Suryakiran P, Thomas F, Struyf F. Sustained immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine administered as a two-dose schedule in adolescent girls: Five-year clinical data and modeling predictions from a randomized study. Hum Vaccin Immunother. 2016;12(1):20-9. doi: 10.1080/21645515.2015.1065363. Epub 2015 Jul 15.

  PMID: 26176261 DERIVED

• Boxus M, Lockman L, Fochesato M, Lorin C, Thomas F, Giannini SL. Antibody avidity measurements in recipients of Cervarix vaccine following a two-dose schedule or a three-dose schedule. Vaccine. 2014 May 30;32(26):3232-6. doi: 10.1016/j.vaccine.2014.04.005. Epub 2014 Apr 13.

  PMID: 24731816 DERIVED

• Romanowski B, Schwarz TF, Ferguson LM, Ferguson M, Peters K, Dionne M, Schulze K, Ramjattan B, Hillemanns P, Behre U, Suryakiran P, Thomas F, Struyf F. Immune response to the HPV-16/18 AS04-adjuvanted vaccine administered as a 2-dose or 3-dose schedule up to 4 years after vaccination: results from a randomized study. Hum Vaccin Immunother. 2014;10(5):1155-65. doi: 10.4161/hv.28022. Epub 2014 Feb 27.

  PMID: 24576907 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Papillomavirus Infections; Virus Diseases; Uterine Cervical Neoplasms

Interventions

human papillomavirus vaccine, L1 type 16, 18; halofantrine; Papillomavirus Vaccines

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Limitations and Caveats

If appropriate, describe significant limitations of the trial. Examples: Early termination leading to small number of subjects analyzed; Technical problems with measurement leading to unreliable or uninterpretable data.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2007
• First Posted: October 10, 2007
• Study Start: October 17, 2007
• Primary Completion: March 18, 2013
• Study Completion: March 18, 2013
• Last Updated: August 17, 2018
• Results First Posted: April 17, 2014

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will share

Locations

CA (5); DE (20)