Study on a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW Conjugate Vaccine) Compared to a Meningococcal Reference Vaccine, and When Given Alone or With Two Other Vaccines in Healthy Adolescents

• ClinicalTrials.gov Identifier: NCT04490018
• Recruitment Status: Recruiting
• First Posted: July 28, 2020
• Last Update Posted: April 21, 2021
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Description

Brief Summary:

Primary Objective:

To demonstrate the non-inferiority of the seroprotection rate (serum bactericidal assay using human complement [hSBA] titer ≥ 1:8) to meningococcal serogroups A, C, W, and Y following the administration of a single dose of MenACYW conjugate vaccine (Group 1) compared to a single dose of Nimenrix® (Group 2)

Secondary Objective:

To describe:

• the antibody response of meningococcal serogroups A, C, W, and Y measured by hSBA, before and 1 month following meningococcal vaccination administered alone (Groups 1 and 2) or concomitantly with 9-valent human papilloma virus (9vHPV) and tetanus, diphtheria, and acellular pertussis - inactivated polio vaccine [adsorbed, reduced antigen(s) content] (Tdap-IPV) vaccines (Group 3)
• the antibody response against antigens of 9vHPV and Tdap-IPV vaccines, before and 1 month following vaccination
• the safety profile in each group after each and any vaccination

Condition or disease	Intervention/treatment	Phase
Meningococcal Infection (Healthy Volunteers)	Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine MenACYW conjugate vaccine; Biological: Meningococcal group A, C, W-135, and Y conjugate vaccine; Biological: Human Papillomavirus 9-valent Vaccine 9vHPV; Biological: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine Tdap-IPV	Phase 3

Detailed Description:

The duration of study participation for each participant will be approximately 30 to 60 days, including 2 or 3 visits (1 or 2 vaccination visit) and 1 or 2 telephone calls, depending on study Group.

* This is the first dose of 9vHPV, of the 2-dose or 3-dose series according to the local recommendations and age of the participant. These additional vaccinations for the completion of 9vHPV schedule will take place outside of the objectives and scope of this study and thus will not be described in this protocol.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 464 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a parallel group prevention study with 2 groups that are observer blind (only the person administering the vaccine is unblinded), and 1 group that is open-label
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description

The study will be performed in a partially observer-blind fashion:

In Groups 1 and 2

• Investigators and study staff who conduct the safety assessment, participants, parents/legally acceptable representatives, the Sponsor, and laboratory personnel performing the serology testing will be kept blinded to the vaccine received
• Only the study staff who prepare and administer the vaccine and are not involved with the safety evaluation will know which vaccine is administered In Group 3
• Everyone involved in the study (ie, Investigator, study staff, the Sponsor, participants, parents/legally acceptable representatives) will know which vaccine is administered. This open-label design for Group 3 is due to the different vaccination schedule for this group than for Groups 1 and 2

• Primary Purpose: Treatment
• Official Title: Immunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine Versus Nimenrix®, and When Administered Alone or Concomitantly With 9vHPV and Tdap-IPV Vaccines in Healthy Adolescents
• Actual Study Start Date: March 16, 2021
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1 (investigational group - sequential administration); MenACYW conjugate vaccine on Day 01 and 9vHPV* + Tdap-IPV vaccines on Day 31: n=174	Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine MenACYW conjugate vaccine; Pharmaceutical form:Liquid solution for injection Route of administration: Intramuscular; Other Name: MenQuadfi®; Biological: Human Papillomavirus 9-valent Vaccine 9vHPV; Pharmaceutical form:Suspension for injection Route of administration: Intramuscular; Other Name: Gardasil® 9; Biological: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine Tdap-IPV; Pharmaceutical form:Suspension for injection Route of administration: Intramuscular; Other Name: Repevax®/Triaxis®/Adacel®Polio
Active Comparator: Group 2 (control group - sequential administration); Nimenrix® on Day 01 and 9vHPV* + Tdap-IPV vaccines on Day 31: n=174	Biological: Meningococcal group A, C, W-135, and Y conjugate vaccine; Pharmaceutical form:Powder and solvent for solution for injection Route of administration: Intramuscular; Other Name: Nimenrix®; Biological: Human Papillomavirus 9-valent Vaccine 9vHPV; Pharmaceutical form:Suspension for injection Route of administration: Intramuscular; Other Name: Gardasil® 9; Biological: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine Tdap-IPV; Pharmaceutical form:Suspension for injection Route of administration: Intramuscular; Other Name: Repevax®/Triaxis®/Adacel®Polio
Experimental: Group 3 (investigational group - concomitant administration); MenACYW conjugate vaccine + 9vHPV* + Tdap-IPV vaccines on Day 01: n=116	Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine MenACYW conjugate vaccine; Pharmaceutical form:Liquid solution for injection Route of administration: Intramuscular; Other Name: MenQuadfi®; Biological: Human Papillomavirus 9-valent Vaccine 9vHPV; Pharmaceutical form:Suspension for injection Route of administration: Intramuscular; Other Name: Gardasil® 9; Biological: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine Tdap-IPV; Pharmaceutical form:Suspension for injection Route of administration: Intramuscular; Other Name: Repevax®/Triaxis®/Adacel®Polio

Outcome Measures

Primary Outcome Measures :

1. Seroprotection against meningococcal serogroups A, C, W, and Y: Group 1 and Group 2 [ Time Frame: Day 31 ]
   Antibody titers measured by hSBA in Groups 1 and 2 Seroprotection defined as antibody titer equal or greater than (≥) 1:8

Secondary Outcome Measures :

1. Antibody titers against meningococcal serogroups A, C, W, and Y [ Time Frame: Day 01 (pre-vaccination) and Day 31 (post-vaccination) ]
   Antibody titers measured by hSBA in each group
2. Antibodies titers against antigens contained in Tdap-IPV vaccine: Group 1 and Group 2 [ Time Frame: Day 31 (pre-vaccination) and Day 61 (post-vaccination) ]
   Anti-Polio 1, 2, and 3 antibody titers measured in Group 1 and Group 2
3. Antibodies titers against antigens contained in Tdap-IPV vaccine: Group 3 [ Time Frame: Day 01 (pre-vaccination) and Day 31 (post-vaccination) ]
   Anti-Polio 1, 2, and 3 antibody titers measured in Group 3
4. Antibodies concentrations against antigens contained in Tdap-IPV vaccine: Group 1 and Group 2 [ Time Frame: Day 31 (pre-vaccination) and Day 61 (post-vaccination) ]
   Anti-tetanus, anti-diphtheria and anti-pertussis antibody concentrations measured in Group 1 and Group 2
5. Antibodies concentrations against antigens contained in Tdap-IPV vaccine: Group 3 [ Time Frame: Day 01 (pre-vaccination) and Day 31 (post-vaccination) ]
   Anti-tetanus, anti-diphtheria and anti-pertussis antibody concentrations measured in Group 3
6. Antibodies titers against antigens contained in HPV vaccine: Group 1 and Group 2 [ Time Frame: Day 31 (pre-vaccination) and Day 61 (post-vaccination) ]
   Anti-HPV antibody titers measured in Group 1 and Group 2
7. Antibodies titers against antigens contained in HPV vaccine: Group 3 [ Time Frame: Day 01 (pre-vaccination) and Day 31 (post-vaccination) ]
   Anti-HPV antibody titers measured in Group 3
8. Number of participants reporting immediate adverse events (AEs) [ Time Frame: Within 30 minutes post-vaccination ]
   Unsolicited systemic AEs reported in the 30 minutes after each vaccination
9. Number of participants reporting solicited injection site reactions and systemic reactions [ Time Frame: Within 7 days post-vaccination ]
   Solicited (prelisted in the participant's diary card and [electronic] Case Report Form [CRF]) injection site and systemic reactions starting any time from the day of vaccination through 7 days after each vaccination Injection site reactions: pain, erythema and swelling Systemic reactions: fever, headache, malaise, myalgia
10. Number of participants reporting unsolicited non-serious AEs [ Time Frame: Within 30 days post-vaccination ]
    Unsolicited (recorded in a diary card) non-serious AEs reported up to 30 days after each vaccination
11. Number of participants reporting serious adverse events (SAEs) [ Time Frame: Up to Day 61 post-vaccination ]
    Serious adverse events (SAEs) (including adverse events of special interest [AESIs]) reported throughout the study, i.e., from Day 01 (first vaccination) to the last study day (Day 61 for Groups 1 and 2 and Day 31 for Group 3)

Eligibility Criteria

• Ages Eligible for Study: 10 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion criteria :

• Aged 10 to 17 years on the day of inclusion ("10 to 17 years" means from the day of the 10th birthday to the day before the 18th birthday)
• Meningococcal C conjugate (MenC) naïve participants or participants having received monovalent MenC priming in infancy (< 2 years of age)
• Assent form has been signed and dated by the participant, and informed consent form has been signed and dated by the parent/ legally acceptable representative
• Participants and parent/legally acceptable representative are able to attend all scheduled visits and to comply with all study procedures
• Covered by health insurance, if required by local regulations

Exclusion criteria:

• Participant is pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after last vaccination. To be considered of non-childbearing potential, a female must be pre-menarche
• Previous vaccination against meningococcal disease with either the study vaccine or another vaccine (ie, polysaccharide, or conjugate meningococcal vaccine containing serogroups A, C, W, or Y; or meningococcal B serogroup-containing vaccine), except licensed monovalent MenC vaccination received before 2 years of age
• Participation at the time of study enrollment (or in the 4 weeks preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure
• Receipt of any vaccine in the 4 weeks preceding any study vaccination or planned receipt of any vaccine in the 4 weeks following any study vaccination except for influenza vaccination, which may be received at least 2 weeks before study vaccines. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines.
• History of vaccination with any tetanus, diphtheria, pertussis, or inactivated polio virus vaccine within the previous 3 years
• Previous human papilloma virus (HPV) vaccination
• Receipt of immune globulins, blood or blood-derived products in the past 3 months
• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
• History of meningococcal infection, confirmed either clinically, serologically, or microbiologically
• Known history of diphtheria, tetanus, pertussis, poliomyelitis, and/or HPV infection or disease. At high risk for meningococcal infection during the study (specifically but not limited to participants with persistent complement deficiency, with anatomic or functional asplenia, or participants travelling to countries with high endemic or epidemic disease)
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances
• Personal history of Guillain-Barré syndrome
• Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine within at least 10 years of the proposed study vaccination
• Personal history of new or past encephalopathy, progressive or unstable neurological disorder, or unstable epilepsy
• Verbal report of thrombocytopenia, contraindicating intramuscular vaccination
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
• Current alcohol abuse or drug addiction
• Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with study conduct or completion
• Moderate or severe acute illness/infection (according to Investigator's judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0 C [≥ 100.4 F]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided
• Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw
• Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (ie, parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Contacts and Locations

Contacts

Contact: Trial Transparency email recommended (Toll free number for US & Canada); 800-633-1610 ext option 6; Contact-US@sanofi.com

Locations

Italy

Investigational Site Number 3800001; Recruiting

Genova, Italy, IT-16132

Investigational Site Number 3800004; Recruiting

Palermo, Italy, 90131

Spain

Investigational site number 7240011; Recruiting

Burriana, Spain, 12530

Investigational site number 7240007; Recruiting

Puzol, Spain, 46530

Investigational Site Number 7240001; Recruiting

Sevilla, Spain, 41013

Investigational site number 7240008; Recruiting

Valencia, Spain, 46011

Investigational site number 7240004; Recruiting

Valencia, Spain, 46020

Investigational site number 7240010; Recruiting

Valencia, Spain, 46022

Investigational site number 7240012; Recruiting

Valencia, Spain, 46024

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT04490018
• Other Study ID Numbers: MEQ00071; 2020-001665-37 ( EudraCT Number ); U1111-1249-2973 ( Other Identifier: UTN )
• First Posted: July 28, 2020
• Last Update Posted: April 21, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Meningococcal Infections; Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs