Safety and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Meningococcal B Recombinant Vaccine When Administered Concomitantly With Routine Vaccines to Healthy Infants of 2 Months of Age and Older, in Taiwan.

Infections, Meningococcal Clinical Trial

Official title:

A Phase 3, Open Label, Randomized, Controlled, Multi-Center Study to Evaluate the Safety and Immunogenicity of GSK Biologicals' Meningococcal B Recombinant Vaccine When Administered Concomitantly With Routine Vaccines to Healthy Infants in Taiwan.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02173704
• Other study ID #: 205249
• Secondary ID: V72_602014-00556
• Status: Completed
• Phase: Phase 3
• Start date: September 11, 2014
• Est. completion date: June 17, 2016

Study information

• Verified date: August 2020
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Assess the safety and immunogenicity of a 3-dose schedule (at 2, 4, 6 months) of GSK Biologicals' Meningococcal B recombinant vaccine followed by a booster at 12 months when concomitantly administered with routine vaccines in healthy infants in Taiwan.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 225
• Est. completion date: June 17, 2016
• Est. primary completion date: December 25, 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Days to 89 Days

Eligibility

Inclusion Criteria:

1. healthy 2-month old infants (55-89 days, inclusive), who were born after full term pregnancy with an estimated gestational age = 37 weeks and a birth weight = 2.5 kg;

2. for whom a parent/legal guardian has given written informed consent after the nature of the study has been explained;

3. available for all the visits scheduled in the study;

4. in good health as determined by medical history, physical examination and clinical judgment of the investigator.

Exclusion Criteria:

1. History of any meningococcal vaccine administration;

2. Prior vaccination with any Diphtheria, Tetanus, Pertussis (acellular or whole cell), Polio (either Inactivated or Oral), Haemophilus influenzae type b (Hib), Pneumococcal, MMR or varicella antigens;

3. Previous ascertained or suspected disease caused by N. meningitidis;

4. Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis;

5. History of severe allergic reaction after previous vaccinations or hypersensitivity to any vaccine component;

6. Significant acute or chronic infection within the previous 7 days or body temperature higher or equal to 38C degrees within the previous day;

7. Antibiotics within 6 days prior to enrollment;

8. Any serious chronic or progressive disease according to the judgment of the investigator (e.g., neoplasm, insulin dependent diabetes mellitus Type I, cardiac disease, hepatic disease, progressive neurological disease or seizure, either associated with fever or as part of an underlying neurological disorder or syndrome, autoimmune disease, HIV infection or AIDS, or blood dyscrasias or diathesis, signs of cardiac or renal failure or severe malnutrition);

9. Known or suspected impairment/alteration of the immune system, immunosuppressive therapy, use of systemic corticosteroids or chronic use of inhaled high-potency corticosteroids since birth;

10. Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation;

11. Receipt of, or intent to immunize with any other vaccine(s) (with the exception of rotavirus vaccine, influenza vaccine and second HepB vaccine), within 28 days prior and throughout the study period. Furthermore, subjects must have received HepB vaccine preferably at 0, 1 month of age, with the second dose at least 14 days prior to study vaccination. Influenza vaccine should be administered at least 14 days before or 14 days after study vaccination; Rotavirus vaccine may be administered during the study as per local practice.

12. Participation in another clinical trial since birth or planned for during study;

13. Family members and household members of research staff;

14. Any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.

Related Conditions & MeSH terms

• Infections, Meningococcal
• Meningococcal Disease
• Meningococcal Infections

Intervention

Biological:
• Bexsero®
Four doses administered in the anterolateral area of the right or left thigh.
• Routine vaccines
Infanrix-IPV + Hib®, Prevenar-13®, Engerix-B®, Priorix® and Varilrix® administered in the anterolateral area of the right or left thigh.

Locations

Country	Name	City	State
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei

Sponsors (2)

Lead Sponsor	Collaborator
GlaxoSmithKline	Novartis Vaccines

Country where clinical trial is conducted

Taiwan, 

References & Publications (1)

Chiu NC, Huang LM, Willemsen A, Bhusal C, Arora AK, Reynoso Mojares Z, Toneatto D. Safety and immunogenicity of a meningococcal B recombinant vaccine when administered with routine vaccines to healthy infants in Taiwan: A phase 3, open-label, randomized study. Hum Vaccin Immunother. 2018 May 4;14(5):1075-1083. doi: 10.1080/21645515.2018.1425659. Epub 2018 Feb 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects With Human Serum Bactericidal Activity (hSBA) Titer = 1:5 Against Neisseria Meningitidis Serogroup B Strains	Percentage of subjects with hSBA titer = 1:5 at 1 month following the third vaccination (at 7 months of age) against the indicator strains H44/76, 5/99, NZ98/254 and strain M10713 when Bexsero® was given concomitantly with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13® and Engerix-B®).	At Day 1 and at one month after the third vaccination (Day 152)
Primary	Percentage of Subjects With Human Serum Bactericidal Assay (hSBA) Titer = 1:4 Against Neisseria Meningitidis Serogroup B Strains	Percentage of subjects with hSBA titer = 1:4 at 1 month after third vaccination (at 7 months of age) against the indicator strains H44/76, 5/99, NZ98/254 and strain M10713 when Bexsero® was given concomitantly with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13® and Engerix-B®).	At Day 1 and at one month after third vaccination (Day 152)
Secondary	Percentage of Subjects With hSBA Titer = 1:5 Against Neisseria Meningitidis Serogroup B, When Bexsero® Booster Was Given With Routine Vaccines (Priorix® + Varilrix® Vaccines)	Percentage of subjects with hSBA titer = 1:5 before booster vaccination and after booster vaccination when Bexsero® booster dose was given with routine vaccines (Priorix® + Varilrix® vaccine) as compared to when only routine vaccines were administered.	At Day 305 and Day 335
Secondary	hSBA Geometric Mean Titers (GMTs) Against Neisseria Meningitidis Serogroup B Indicator Strains, When Bexsero® Vaccine Was Given With Routine Vaccines	hSBA GMTs against the indicator strains H44/76, 5/99, NZ98/254 and strain M10713 was evaluated at baseline (2 months of age, Day 1), 1 month after the third vaccination with Bexsero® with concomitant routine vaccines (Infanrix-IPV+Hib®, Prevenar-13®, Engerix®) (7 months of age, Day 152) or prior to the booster dose of Bexsero® with routine vaccines (Priorix®, Varilrix®) (12 months of age, Day 305) and 1 month after the booster dose (13 months of age, Day 335), as compared to when only routine vaccines were administered.	At Day 1, Day 152, Day 305 and Day 335
Secondary	hSBA Geometric Mean Ratios (GMRs) Against Neisseria Meningitidis Serogroup B Strains.	GMRs of post-vaccination versus pre-vaccination of hSBA titer against the indicator strains H44/76, 5/99, NZ98/254 and strain M10713 were evaluated at one month after the third vaccination with Bexsero® vaccine and concomitant routine vaccines (Infanrix-IPV+Hib®, Prevenar-13® and Engerix®) (Day 152) compared to baseline (Day 1) or at one month after the booster dose of Bexsero® vaccine with routine vaccines (Priorix®, Varilrix®) (Day 335) compared to prior to the booster dose (Day 305).	At Day 1, Day 152, Day 305 and Day 335
Secondary	Percentages of Subjects With hSBA Titers =1:8 Against Neisseria Meningitidis Serogroup B, When Bexsero® Vaccine Was Given With Routine Vaccines	Percentages of subjects with hSBA titers =1:8 against N.meningitidis serogroup B strains, at one month after concomitant administration of third primary dose of Bexsero® with routine vaccines [Infanrix-IPV + Hib®, Prevenar-13® and Engerix-B®] and at one month after concomitant administration of Bexsero® booster dose with routine vaccines [Priorix® and Varilrix® vaccine],as compared to when only routine vaccines were administered.	At Day 1,Day 152,Day 305, Day 335
Secondary	Number of Subjects Reporting Solicited Local Adverse Events (AEs) After Receiving Bexsero® Vaccine With Routine Vaccine or Routine Vaccines Alone, at 2, 4, 6 and 12 Months of Age.	Number of subjects reporting solicited local AEs following concomitant administration of Bexsero® vaccine with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13® and Engerix-B® at 2, 4 and 6 months of age and Priorix® and Varilrix® at 12 months of age)compared to when only routine vaccines were administered alone at 2,4,6 and 12 months. Solicited local symptoms assessed were Erythema, Induration, Swelling and Tenderness.	From day 1 (6 hours) to day 7 after each vaccination (1st, 2nd, 3rd and 4th vaccination)
Secondary	Number of Subjects Reporting Solicited Systemic Adverse Events (AEs) After Receiving Bexsero® Vaccine With Routine Vaccine or Routine Vaccines Alone, at 2, 4, 6 and 12 Months of Age.	Number of subjects reporting solicited systemic AEs following concomitant administration of Bexsero® vaccine with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13® and Engerix-B® at 2, 4 and 6 months of age and Priorix® and Varilrix® at 12 months of age) compared to when only routine vaccines were alone, at 2, 4, 6 and 12 months. Systemic solicited symptoms assessed were Change in Eating Habits, Diarrhea, Irritability, Persistent Crying, Rash, Sleepiness, Vomiting and Fever (body temperature = 38.0 °C)	From day 1 (6 hours) to day 7 after each vaccination
Secondary	Number of Subjects Reporting Solicited Systemic AEs After Receiving Priorix® and Varilrix® Routine Vaccines (With and Without Bexsero® Vaccine) at 12 Months of Age.	Number of subjects who reported solicited systemic AEs reported after the administration of Varilrix® and Priorix® vaccines (with and without Bexsero® vaccine) at 12 months of age. Solicited systemic AEs assessed were Rash, Lymphadenopathy and Fever. This analysis was conducted for a prolonged period of 28 Days following Varilrix® and Priorix® administration.	From Day 1 to Day 28 after vaccination
Secondary	Number of Subjects Reporting Unsolicited Adverse Events After Receiving Bexsero® Vaccination With Routine Vaccines	Number of subjects reporting any unsolicited AEs following concomitant administration of Bexsero® vaccine with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13®, Engerix-B® or Priorix® and Varilrix®) compared to when only routine vaccines were administered alone.	From day 1 to day 7 after each vaccination
Secondary	Number of Subjects Reporting Serious Adverse Events (SAEs), Medically Attended AEs (MAEs) and AEs Leading to Premature Withdrawal and Death and AEs Leading to Hospitalization.	Number of subjects reporting SAEs, medically attended AEs and AEs leading to premature withdrawal from the study and leading to death and AEs leading to hospitalization following concomitant administration of Bexsero® vaccine with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13®, Engerix-B®, Priorix® and Varilrix®) compared to when only routine vaccines were administered alone. SAEs assessed included medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Possibly or probably related SAE were SAEs assessed by the investigator as related to the vaccination. Medically attended AEs were events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason.	Throughout the study period (Day 1 to Day 335)

External Links

•   IPD for this study will be made available via the Clinical Study Data Request site.