A Study on the Immune Response and Safety of an Adjuvanted Human Papillomavirus Vaccine When Given to Healthy Women 16 to 26 Years of Age

NCT05496231 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2137492022-000090-15
• Study Type: interventional
• Target: 1,080
• Locations: 8 countries
• Sites: 68

Brief Summary

The main purpose of this study was to evaluate the safety and reactogenicity of GlaxoSmithKline Biologicals SA (GSK)'s investigational adjuvanted human papillomavirus (HPV) vaccine formulations.

Conditions

Cervical Intraepithelial Neoplasia

Keywords

Human papillomavirus; Infection; Vaccine; Women's health

Outcome Measures

Primary Outcomes (14)

• Number of Participants Reporting Grade 3 Solicited Administration Site Events After Vaccine Dose 1

  Assessed solicited administration site events included pain, redness and swelling at injection site. Grade 3 pain = significant pain at rest, which prevented normal everyday activities. Grade 3 redness/swelling = redness/swelling with a surface diameter greater than (\>) 50 millimeters (mm).

  Within 7 days after vaccine Dose 1 (administered at Day 1)

• Number of Participants Reporting Grade 3 Solicited Administration Site Events After Vaccine Dose 2

  Assessed solicited administration site events included pain, redness and swelling at injection site. Grade 3 pain = significant pain at rest, which prevented normal everyday activities. Grade 3 redness/swelling = redness/swelling with a surface diameter \>50 mm.

  Within 7 days after vaccine Dose 2 (administered at Month 2)

• Number of Participants Reporting Grade 3 Solicited Administration Site Events After Vaccine Dose 3

  Assessed solicited administration site events included pain, redness and swelling at injection site. Grade 3 pain = significant pain at rest, which prevented normal everyday activities. Grade 3 redness/swelling = redness/swelling with a surface diameter \>50 mm.

  Within 7 days after vaccine Dose 3 (administered at Month 6)

• Number of Participants Reporting Grade 3 Solicited Systemic Events After Vaccine Dose 1

  Assessed solicited systemic events included fever, headache, myalgia, arthralgia and fatigue. Grade 3 fever = body temperature \>39.0 degrees Celsius (°C) or 102.2 Fahrenheit (°F). The preferred location for measuring temperature was the axilla. Grade 3 headache, myalgia, arthralgia and fatigue = symptoms that prevented normal, every day activities.

  Within 7 days after vaccine Dose 1 (administered at Day 1)

• Number of Participants Reporting Grade 3 Solicited Systemic Events After Vaccine Dose 2

  Assessed solicited systemic events included fever, headache, myalgia, arthralgia and fatigue. Grade 3 fever = body temperature \>39.0°C or 102.2°F. The preferred location for measuring temperature was the axilla. Grade 3 headache, myalgia, arthralgia and fatigue = symptoms that prevented normal, every day activity.

  Within 7 days after vaccine Dose 2 (administered at Month 2)

• Number of Participants Reporting Grade 3 Solicited Systemic Events After Vaccine Dose 3

  Assessed solicited systemic events included fever, headache, myalgia, arthralgia and fatigue. Grade 3 fever = body temperature \>39.0°C or 102.2°F. The preferred location for measuring temperature was the axilla. Grade 3 headache, myalgia, arthralgia and fatigue = symptoms that prevented normal, every day activity.

  Within 7 days after vaccine Dose 3 (administered at Month 6)

• Number of Participants Reporting Grade 3 Unsolicited Adverse Events (AEs) After Vaccine Dose 1

  An unsolicited AE is defined as an AE that was not included in the list of solicited events using an eDiary and that was spontaneously communicated by a participant/participant's parent(s)/legally acceptable representative(s) \[LAR(s)\] who has signed the informed consent. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited AE. Grade 3 unsolicited AEs = an AE which prevented normal, everyday activities.

  Within 28 days after vaccine Dose 1 (administered at Day 1)

• Number of Participants Reporting Grade 3 Unsolicited AEs After Vaccine Dose 2

  An unsolicited AE is defined as an AE that was not included in the list of solicited events using an eDiary and that was spontaneously communicated by a participant/participant's parent(s)/LAR(s) who has signed the informed consent. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited AE. Grade 3 unsolicited AEs = an AE which prevented normal, everyday activities.

  Within 28 days after vaccine Dose 2 (administered at Month 2)

• Number of Participants Reporting Grade 3 Unsolicited AEs After Vaccine Dose 3

  An unsolicited AE is defined as an AE that was not included in the list of solicited events using an eDiary and that was spontaneously communicated by a participant/ participant's parent(s)/LAR(s) who has signed the informed consent. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited AE. Grade 3 unsolicited AEs = an AE which prevented normal, everyday activities.

  Within 28 days after vaccine Dose 3 (administered at Month 6)

• Number of Participants Reporting Serious Adverse Events (SAEs)

  An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, or resulted in abnormal pregnancy outcomes, or in other situations that were considered serious per medical or scientific judgment.

  From first vaccination (Day 1) to study end (Month 12)

• Number of Participants in Step 1 Subset With Clinically Relevant Biochemical Abnormalities

  As pre-specified in the protocol, the assessed biochemical parameters were blood urea nitrogen (BUN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Assessment of intensity: Grading of the biochemical parameters was based on the institutional normal reference ranges and derived from the standard Food and Drug Administration (FDA) Toxicity Grading Scale. Changes compared to normal reference ranges were graded as follows: Grade 0 = a non-missing parameter value for which grade could not be derived according to the grading scale and does not belong to Grade 1-4; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life-Threatening. Unknown = parameter value missing for the specified parameter.

  At Day 7

• Number of Participants in Step 1 Subset With Clinically Relevant Hematological Abnormalities

  As pre-specified in the protocol, the assessed hematological parameters were hemoglobin, white blood cells (WBC) increase, WBC decrease, lymphocyte decrease, neutrophils decrease, eosinophils, and platelets decrease. Assessment of intensity: Grading of the biochemical parameters was based on the institutional normal reference ranges and derived from the standard FDA Toxicity Grading Scale. Changes compared to normal reference ranges were graded as follows: Grade 0 = a non-missing parameter value for which grade could not be derived according to the grading scale and does not belong to Grade 1-4; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life-Threatening; Unknown = parameter value missing for the specified parameter.

  At Day 7

• Number of Participants in Step 1 Subset With Clinically Relevant Abnormalities in Hemoglobin Change From Baseline Levels

  The number of participants with clinically relevant abnormalities in hemoglobin change from baseline levels is reported. Assessment of intensity: Grading of the biochemical parameters was based on the institutional normal reference ranges and derived from the standard FDA Toxicity Grading Scale. Changes compared to normal reference ranges were graded as follows: Grade 0 = a non-missing parameter value for which grade could not be derived according to the grading scale and does not belong to Grade 1-4; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life-Threatening; Unknown = parameter value missing for the specified parameter. Change from baseline = the difference between a participant's baseline (pre-intervention) parameter values and their follow-up (post-intervention) parameter values.

  At Day 7 compared to baseline (Day 1)

• Anti-HPV Immunoglobulin G (IgG) Antibody Concentrations

  Anti-HPV IgG antibody concentrations were determined by electrochemiluminescence (ECL) assay and expressed as geometric mean concentrations (GMCs) in arbitrary units per milliliter (AU/mL). The assessed antigens were: HPV 6, HPV 11, HPV 16, HPV 18, HPV 31, HPV 33, HPV 45, HPV 52 and HPV 58 type antigens.

  At Month 7 (one month after vaccine Dose 3 administration)

Secondary Outcomes (12)

• Number of Participants Reporting Any Solicited Administration Site Events

  Within 7 days after each vaccine dose (administered at Day 1, Month 2, and Month 6)

• Number of Participants Reporting Any Solicited Systemic Events

  Within 7 days after each vaccine dose (administered at Day 1, Month 2, and Month 6)

• Number of Participants Reporting Any Unsolicited AEs

  Within 28 days after each vaccine dose (administered at Day 1, Month 2, and Month 6)

• Number of Participants Reporting Potential Immune-mediated Diseases (pIMDs)

  From first vaccination (Day 1) to study end (Month 12)

• Number of Participants Reporting Pregnancies

  From Day 1 of pregnancy to study end (Month 12)

Study Arms (4)

HPV9 High Group

EXPERIMENTAL

Participants received 3 doses of the high formulation of Human Papilloma Virus 9-valent (HPV9) investigational adjuvanted vaccine at Day 1, Month 2, and Month 6.

Biological: HPV9 High formulation

HPV9 Med Group

EXPERIMENTAL

Participants received 3 doses of the medium formulation of Human Papilloma Virus 9-valent (HPV9) investigational adjuvanted vaccine at Day 1, Month 2, and Month 6.

Biological: HPV9 Medium formulation

HPV9 Low Group

EXPERIMENTAL

Participants received 3 doses of the low formulation of Human Papilloma Virus 9-valent (HPV9) investigational adjuvanted vaccine at Day 1, Month 2, and Month 6.

Biological: HPV9 Low formulation

Gar9 Group

ACTIVE COMPARATOR

Participants received 3 doses of the marketed Human Papilloma Virus (HPV) vaccine (Gardasil 9) at Day 1, Month 2, and Month 6.

Biological: Gardasil 9

Interventions

HPV9 High formulation BIOLOGICAL

3 doses of the high formulation of HPV9 investigational adjuvanted vaccine were administered intramuscularly at Day 1, Month 2 and Month 6.

HPV9 High Group

HPV9 Medium formulation BIOLOGICAL

3 doses of the medium formulation of HPV9 investigational adjuvanted vaccine were administered intramuscularly at Day 1, Month 2 and Month 6.

HPV9 Med Group

HPV9 Low formulation BIOLOGICAL

3 doses of the low formulation of HPV9 investigational adjuvanted vaccine were administered intramuscularly at Day 1, Month 2 and Month 6.

HPV9 Low Group

Gardasil 9 BIOLOGICAL

3 doses of the marketed HPV vaccine (Gardasil 9) were administered intramuscularly at Day 1, Month 2 and Month 6.

Gar9 Group

Eligibility Criteria

• Age: 16 Years - 26 Years
• Gender Eligibility Details: Only female participants, between 16-26 years of age were included in the study.
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Healthy participants as established by medical history and clinical examination before entering into the study.
• For Step 1 only: Female between and including 18 and 26 years of age at the time of the first study intervention administration.
• For Step 2: Female between and including 16 and 26 years of age at the time of the first study intervention administration.
• Written informed consent obtained from the participant prior to performance of any study specific procedure (for participants below the legal age of consent as per local regulations, written informed consent must be obtained from the participant/participant's parent\[s\]/legally authorized representatives \[LAR{s}\] and, in addition, the participant should sign and personally date a written informed assent).
• Participants and/or participants' parent(s)/LAR(s) who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the eDiary, return for follow-up visits).
• Female participant with no more than 4 lifetime sexual partners prior to enrollment.
• Female participants of non-childbearing potential may be enrolled in the study.
• Female participants of childbearing potential may be enrolled in the study if the participant:
• has practiced adequate highly effective contraception for at least 1 month prior to study intervention administration, and
• has a negative pregnancy test on the day of study intervention administration, and
• has agreed to continue adequate contraception during the entire intervention period and for 2 months after completion of the study intervention administration series.

You may not qualify if:

• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s).
• History or current diagnosis of autoimmune disease.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• Hypersensitivity to latex.
• Major congenital defects, as assessed by the investigator.
• History of abnormal Papanicolaou test or abnormal cervical biopsy result.
• History of external genital/vaginal warts.
• History of positive HPV test.
• Acute or chronic clinically significant pulmonary, cardiovascular, neurologic, hepatic or renal functional abnormality, as determined by physical examination or laboratory tests
• Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.
• Previous vaccination against HPV.
• Previous exposure to monophosphoryl lipid A (MPL) or AS04 adjuvant.
• Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study intervention(s) during the period beginning 30 days before the first dose of study intervention(s) (Day -29 to Day 1), or their planned use during the study period.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (68)

GSK Investigational Site

San Diego, California, 92103-6204, United States

Location

GSK Investigational Site

San Diego, California, 92120, United States

Location

GSK Investigational Site

Wheat Ridge, Colorado, 80033, United States

Location

GSK Investigational Site

Coral Gables, Florida, 33134, United States

Location

GSK Investigational Site

Kissimmee, Florida, 34741, United States

Location

GSK Investigational Site

Miami, Florida, 33125, United States

Location

GSK Investigational Site

North Miami Beach, Florida, 33162, United States

Location

GSK Investigational Site

Pompano Beach, Florida, 33060, United States

Location

GSK Investigational Site

Sarasota, Florida, 34239, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30328, United States

Location

GSK Investigational Site

Evansville, Indiana, 47712, United States

Location

GSK Investigational Site

South Bend, Indiana, 46617, United States

Location

GSK Investigational Site

Topeka, Kansas, 66606, United States

Location

GSK Investigational Site

Wichita, Kansas, 67205, United States

Location

GSK Investigational Site

Lexington, Kentucky, 40509, United States

Location

GSK Investigational Site

Covington, Louisiana, 70433, United States

Location

GSK Investigational Site

Elkridge, Maryland, 21075, United States

Location

GSK Investigational Site

Saginaw, Michigan, 48602, United States

Location

GSK Investigational Site

Jefferson City, Missouri, 65109, United States

Location

GSK Investigational Site

Las Vegas, Nevada, 89102, United States

Location

GSK Investigational Site

Albuquerque, New Mexico, 87102, United States

Location

GSK Investigational Site

Raleigh, North Carolina, 27612, United States

Location

GSK Investigational Site

Columbus, Ohio, 43213, United States

Location

GSK Investigational Site

Norman, Oklahoma, 73072, United States

Location

GSK Investigational Site

North Charleston, South Carolina, 29405, United States

Location

GSK Investigational Site

Chattanooga, Tennessee, 37404, United States

Location

GSK Investigational Site

Carrollton, Texas, 75010, United States

Location

GSK Investigational Site

Corpus Christi, Texas, 78412, United States

Location

GSK Investigational Site

Dallas, Texas, 75251, United States

Location

GSK Investigational Site

Fort Worth, Texas, 76104, United States

Location

GSK Investigational Site

Houston, Texas, 77065, United States

Location

GSK Investigational Site

Humble, Texas, 77338, United States

Location

GSK Investigational Site

Humble, Texas, 77346, United States

Location

GSK Investigational Site

Irving, Texas, 75062, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Tomball, Texas, 77375, United States

Location

GSK Investigational Site

West Jordan, Utah, 84088, United States

Location

GSK Investigational Site

Norfolk, Virginia, 23502, United States

Location

GSK Investigational Site

Norfolk, Virginia, 68701, United States

Location

GSK Investigational Site

Sofia, 1431, Bulgaria

Location

GSK Investigational Site

Sofia, 1606, Bulgaria

Location

GSK Investigational Site

Hradec Králové, CZ-500 03, Czechia

Location

GSK Investigational Site

Olomouc, 772 00, Czechia

Location

GSK Investigational Site

Olomouc, 779 00, Czechia

Location

GSK Investigational Site

Prague, 160000, Czechia

Location

GSK Investigational Site

Tallinn, 10128, Estonia

Location

GSK Investigational Site

Tallinn, 10617, Estonia

Location

GSK Investigational Site

Tartu, 50106, Estonia

Location

GSK Investigational Site

Tartu, 50708, Estonia

Location

GSK Investigational Site

Dijon, 21000, France

Location

GSK Investigational Site

La Roche-sur-Yon, 85025, France

Location

GSK Investigational Site

La Tronche, 38043, France

Location

GSK Investigational Site

Nantes, 44093, France

Location

GSK Investigational Site

Paris, 75679, France

Location

GSK Investigational Site

Rennes, 35000, France

Location

GSK Investigational Site

Tours, 37000, France

Location

GSK Investigational Site

Schwerin, 19055, Germany

Location

GSK Investigational Site

Würzburg, 97074, Germany

Location

GSK Investigational Site

Kaunas, 49387, Lithuania

Location

GSK Investigational Site

Kaunas, LT-48259, Lithuania

Location

GSK Investigational Site

Kaunas, LT-49456, Lithuania

Location

GSK Investigational Site

Kaunas, LT-50177, Lithuania

Location

GSK Investigational Site

Vilnius, 8661, Lithuania

Location

GSK Investigational Site

Bydgoszcz, 85-796, Poland

Location

GSK Investigational Site

Krakow, 30-348, Poland

Location

GSK Investigational Site

Lodz, 91-363, Poland

Location

GSK Investigational Site

Skierniewice, 96-100, Poland

Location

GSK Investigational Site

Warsaw, 00-215, Poland

Location

MeSH Terms

Conditions

Uterine Cervical Dysplasia; Infections

Interventions

Human Papillomavirus Recombinant Vaccine nonavalent

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Observer-blinded for study vs comparator vaccine; double-blinded for 3 formulations of study vaccine
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2022
• First Posted: August 11, 2022
• Study Start: August 22, 2022
• Primary Completion: February 23, 2024
• Study Completion: February 25, 2024
• Last Updated: February 3, 2025
• Results First Posted: February 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

ES (4); CZ (4); PL (5); BU (2); LI (5); FR (7); DE (2); US (39)