Safety, Tolerability and Immunogenicity of a Third Dose of One of Four Different Formulations of rMenB + MenACWY Combination Vaccine in Adolescents Who Previously Received the Same Study Vaccines

Meningococcal Disease Clinical Trial

Official title:

Phase 2, Observer-Blind, Controlled, Randomized, Multi-Center Extension Study to Evaluate Safety, Tolerability and Immunogenicity of a Third Dose of One of Four Different Formulations of rMenB + MenACWY in Adolescents Who Previously Received the Same Study Vaccines

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01367158
• Other study ID #: V102_02E1
• Status: Completed
• Phase: Phase 2
• First received: June 3, 2011
• Last updated: November 17, 2014
• Start date: July 2011
• Est. completion date: July 2012

Study information

• Verified date: November 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Colombia: Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA),Panama: Instituto Conmemorativo Gorgas de Estudios de la Salud (ICGES),Chile: Instituto de Salud Pública de Chile (ISP)
• Study type: Interventional

Clinical Trial Summary

This study will evaluate safety, tolerability, and immunogenicity of a booster dose of a meningococcal vaccine formulation in adolescents.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 440
• Est. completion date: July 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 11 Years to 18 Years

Eligibility

Inclusion Criteria:

Individuals eligible to be enrolled into this study were male or female who completed study V102_02 (primary study), and:

1. who were 11 to 18 years at the time of enrollment in primary study;

2. who had given their written consent at the time of enrollment;

3. who were available for all the visits scheduled in the study (ie, not planning to leave the area before the end of the study period);

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

Exclusion Criteria:

1. History of any meningococcal vaccine administration;

2. Current or previous, confirmed or suspected disease caused by N meningitidis;

3. Household contact with and/or intimate exposure to an individual with any laboratory confirmed N meningitidis infection within 60 days of enrollment;

4. Significant acute or chronic infection within the previous 7 days or fever (defined as temperature >38°C) within the previous 3 days;

5. Antibiotics within 7 days prior to enrollment or blood draw;

6. Pregnancy or nursing (breastfeeding) mothers;

7. Females of childbearing age who had not used or did not plan to use acceptable birth control measures, for the duration of the study. Oral, injected or implanted hormonal contraceptive, barrier methods (condom or diaphragm with spermicide); intrauterine device or sexual abstinence was considered acceptable forms of birth control. If sexually active the subject must have been using one of the accepted birth control methods at least two months prior to study entry;

8. Any serious chronic or progressive disease (eg, neoplasm, diabetes, cardiac disease, hepatic disease, progressive neurological disease or seizure disorder; autoimmune disease, human immunodeficiency virus infection or acquired immunodeficiency syndrome, blood dyscrasias, bleeding diathesis, signs of cardiac or renal failure or severe malnutrition).

9. Known or suspected impairment/alteration of the immune system, immunosuppressive therapy, including use of corticosteroids in immunosuppressive doses or chronic use of inhaled high-potency corticosteroids or immunostimulants within the previous 60 days. Use of topical corticosteroids administered during the study in limited areas (ie, eczema on knees or face or elbows) of the body was allowed;

10. Receipt of blood, blood products and/or plasma derivatives, or a parenteral immunoglobulin preparation within the previous 90 days;

11. History of severe allergic reactions after previous vaccinations or hypersensitivity to any vaccine component;

12. Individuals who received any other vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study or who were planning to receive any vaccine within 4 weeks from the study vaccines.

13. Individuals participating in any clinical trial with another investigational product 30 days prior to first study visit or had intent to participate in another clinical study at any time during the conduct of this study.

14. Individuals who were part of study personnel or close family members conducting this study.

15. Individuals with medical history or any illness that, in the opinion of the investigator, might interfere with the results of the study or posed additional risk to the subjects due to participation in the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Caregiver), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Meningitis
• Meningitis, Meningococcal
• Meningococcal Disease
• Meningococcal Infections
• Meningococcal Meningitis

Intervention

Biological:
• Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine
The lyophilized Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine reconstituted with one dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine
• Meningococcal (group B) multicomponent recombinant adsorbed vaccine
Liquid Meningococcal (group B) multicomponent recombinant adsorbed vaccine
• Tdap
Sterile liquid suspension of tetanus and diphtheria toxoids and acellular pertussis components intended for intramuscular injection

Locations

Country	Name	City	State
Chile	CESFAM Gabriela Mistral:	Aurora de Chile 9872 - San Ramón	Saniago
Chile	Pontificia Universidad Catolica de Chile	Marcoleta 350	Santiago
Colombia	CAFAM	Avenida Carrera 68# 90-88 Piso 4	Bogota
Colombia	CAIMED	Carrera	Bogotá
Colombia	Centro de Investigacion CafeSalud Medicina Prepagada	Carrera 14 No. 94-49 PisoSexto	Bogota
Panama	Indicasat:	Clayton, ciudad del Saber Edificio 219	Panama City
Panama	Health Research International: Centro Especializado san Fernando	Piso numero 5, Consultorio 12; Via Espana, las Sabanas,	Panama city

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Vaccines

Countries where clinical trial is conducted

Chile,  Colombia,  Panama, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentages of Subjects With hSBA =1:8 Against Serogroups A, C, W and Y at One Month After the Third Vaccination With Either One of Four MenABCWY Formulations, rMenB or MenACWY/Placebo	Antibody response was measured as the percentage of subjects with human serum bactericidal assay (hSBA) titers =1:8 and associated 95% CI, directed against to N meningitidis serogroups A, C, W, and Y at 6 months following first vaccine during the parent study NCT01210885 and one month after third vaccination (Month 7).	At month 6 and month 7	No
Primary	Percentages of Subjects With hSBA =1:5 Against Serogroup B Test Strains at One Month After Third Vaccination With One of Four MenABCWY Formulations, rMenB or MenACWY/Placebo	Antibody response was measured as the percentage of subjects with human serum bactericidal assay (hSBA) titers =1:5 and associated 95% CI, directed against to Serogroup B Test Strains at 6 months following first vaccine during the parent study NCT01210885 and one month after third vaccination (Month 7)	At month 6 and month 7	No
Secondary	Geometric Mean Titers (GMT) for N Meningitidis Serogroups A, C, W and Y at One Month After the Third Vaccination With One of Four MenABCWY Formulations, rMenB or MenACWY/Placebo	Antibody response was measured as Geometric Mean hSBA Titers against N meningitidis Serogroups A, C, W and Y at One of Four MenABCWY Formulations or rMenB at 6 months following first vaccine during the parent study NCT01210885 and one month after third vaccination (Month 7)	At month 6 and month 7	No
Secondary	Geometric Mean Ratio (GMR) for (95%CI) for N Meningitidis Serogroups A, C, W and Y at One Month After the Third Vaccination With One of Four MenABCWY Formulations, rMenB or MenACWY/Placebo	Antibody response was measured as Geometric Mean Ratio (95% CI), against N meningitidis Serogroups A, C, W and Y at One Month After the Third Vaccination (month 7) With One of Four MenABCWY Formulations or rMenB	At month 7	No
Secondary	GMT for N Meningitidis Against Serogroup B Test Strains at One Month After the Third Vaccination With One of Four MenABCWY Formulations, rMenB or MenACWY/Placebo	Antibody response was measured as Geometric Mean hSBA Titers Against Serogroup B Test Strains at 6 months following first vaccine during the parent study NCT01210885 and one month after third vaccination (Month 7) with One of Four MenABCWY Formulations, rMenB or MenACWY/Placebo	At month 6 and month 7	No
Secondary	GMR for (95%CI) for N Meningitidis Against Serogroup B Test Strains at One Month After the Third Vaccination With One of Four MenABCWY Formulations, rMenB or MenACWY/Placebo	Antibody response was measured as Geometric Mean Ratio (95% CI), against Serogroup B Test Strains at One Month After the Third Vaccination (month 7) with One of Four MenABCWY Formulations, rMenB or MenACWY/Placebo	At month 7	No
Secondary	Percentages of Subjects With Seroresponse Against N Meningitidis Serogroups A, C, W and Y at 1 Month After the Third Vaccination With One of Four MenABCWY Formulations, rMenB or MenACWY/Placebo	Antibody response was measured as the percentage of subjects with seroresponse Against N meningitidis Serogroups A, C, W and Y, after pre and post vaccination at month 6 and after the third vaccination (month 7) with One of Four MenABCWY Formulations, rMenB or MenACWY/Placebo. Seroresponse to N meningitidis serogroups A, C, W and Y is defined as: For subjects with a prevaccination hSBA <1:4, a postvaccination hSBA =1:8;For subjects with a prevaccination hSBA =1:4, an increase in hSBA titer of at least four times the prevaccination titer.	At month 7	No
Secondary	Percentages of Subjects With 4-fold Increase in hSBA Titers Against Serogroup B Test Strains at One Month After Third Vaccination With One of Four MenABCWY Formulations, rMenB or MenACWY/Placebo	Antibody response was measured as the percentage of subjects with 4-fold Increase in human serum bactericidal assay (hSBA) titers and associated 95% CI, Against Serogroup B Test Strains at One Month After Third Vaccination (month 7) with One of Four MenABCWY Formulations, rMenB or MenACWY/Placebo	At month 7	No
Secondary	GMT for N Meningitidis Serogroups A, C, W and Y at Month 0 Through Month 12 Following Vaccination at Month 0, Month 2 With One of Four MenABCWY Formulations, rMenB, or MenACWY/Placebo	Antibody response was measured as Geometric Mean hSBA Titers Against N meningitidis Serogroups A, C, W and Y after first (month 1) and second (month 3) vaccination during the parent study NCT01210885, after 6 month of the first vaccination (6 month) in the parent study and after the third vaccination (month 7) and 6 month after the third vaccination (month 12) with One of Four MenABCWY Formulations, rMenB, or MenACWY/Placebo.	At month 1, 3, 6, 7 and 12	No
Secondary	GMR for N Meningitidis Serogroups A, C, W and Y at Month 0 Through Month 12 Following Vaccination at Month 0, Month 2 With One of Four MenABCWY Formulations, rMenB, or MenACWY/Placebo	Antibody response was measured as Geometric Mean Ratios (95%CI) Against N meningitidis Serogroups A, C, W and Y after after first (month 1) and second (month 3) vaccination during the parent study NCT01210885, after 6 month of the first vaccination (6 month) in the parent study and after the third vaccination (month 7) and 6 month after the third vaccination (month 12) with One of Four MenABCWY Formulations, rMenB, or MenACWY/Placebo	At month 1, 3, 6, 7 and 12	No
Secondary	GMT Against Serogroup B Test Strains at Month 0 Through Month 12 Following Vaccination at Month 0 and Month 2 With One of Four MenABCWY Formulations, rMenB, or MenACWY/Placebo	Antibody response was measured as Geometric Mean hSBA Titers Against Serogroup B Test Strains after first (month 1) and second (month 3) vaccination during the parent study NCT01210885, After Third Vaccination (month 7) and 6 month after the third vaccination (month 12) with One of Four MenABCWY Formulations, rMenB, or MenACWY/Placebo	At month 1, 3, 6, 7 and 12	No
Secondary	GMR Against Serogroup B Test Strains at Month 0 Through Month 12 Following Vaccination at Month 0 and Month 2 With One of Four MenABCWY Formulations, rMenB, or MenACWY/Placebo	Antibody response was measured as Geometric Mean Ratios (95%CI) Against Serogroup B Test Strains after first (month 1) and second (month 3) vaccination during the parent study NCT01210885, after 6 month of the first vaccination (month 6) in the parent study and after the third vaccination (month 7) and 6 month after the third vaccination (month 12) with One of Four MenABCWY Formulations, rMenB, or MenACWY/Placebo	At month 1, 3, 6, 7 and 12	No
Secondary	GMT Against Serogroups A, C, W, and Y at Month 0 Through Month 12 Following Vaccination at 0, 2 and 6 Months With One of Four MenABCWY Formulations, rMenB, or MenACWY/Placebo	Antibody response was measured as Geometric Mean hSBA Titers Against Serogroup B Test Strains after first (month 1) and second (month 3) vaccination during the parent study NCT01210885, after 6 month of the first vaccination (6 month) in the parent study and after the third vaccination (month 7) and 6 month after the third vaccination (month 12) with One of Four MenABCWY Formulations, rMenB, or MenACWY/Placebo	At month 1, 3, 6, 7 and 12	No
Secondary	GMR Against Serogroups A, C, W, and Y at Month 0 Through Month 12 Following Vaccination at 0, 2 and 6 Months With One of Four MenABCWY Formulations, rMenB, or MenACWY/Placebo	Antibody response was measured as Geometric Mean Ratios (95%CI) Against Serogroup B Test Strains after first (month 1) and second (month 3) vaccination during the parent study NCT01210885, after 6 month of the first vaccination (6 month) in the parent study and after the third vaccination (month 7) and 6 month after the third vaccination (month 12) with One of Four MenABCWY Formulations, rMenB, or MenACWY/Placebo	At month 1, 3, 6, 7 and 12	No
Secondary	GMT Against Serogroup B Test Strains at Month 0 Through Month 12 Following Vaccination at Month 0, 2 and 6 With One of Four MenABCWY Formulations, rMenB, or MenACWY/Placebo	Antibody response was measured as Geometric Mean hSBA Titers Against Serogroup B Test Strains after first (month 1) and second (month 3) vaccination during the parent study NCT01210885, after 6 month of the first vaccination (6 month) in the parent study and after the third vaccination (month 7) and 6 month after the third vaccination (month 12) with One of Four MenABCWY Formulations, rMenB, or MenACWY/Placebo	At month 1, 3, 6, 7 and 12	No
Secondary	GMR Against Serogroup B Test Strains at Month 0 Through Month 12 Following Vaccination at Month 0, 2 and 6 With One of Four MenABCWY Formulations, rMenB, or MenACWY/Placebo	Antibody response was measured as Geometric Mean Ratios (95%CI) Against Serogroup B Test Strains after first (month 1) and second (month 3) vaccination during the parent study NCT01210885, after 6 month of the first vaccination (6 month) in the parent study and after the third vaccination (month 7) and 6 month after the third vaccination (month 12) with One of Four MenABCWY Formulations, rMenB, or MenACWY/Placebo	At month 1, 3, 6, 7 and 12	No
Secondary	Number of Subjects Reporting Unsolicited Adverse Events After Vaccination	Unsolicited AEs were collected with onset from Day 1 through Day 7 After Vaccination. One subject initially randomized to group 3ABCWYqOMV and supposed to receive rMenB+1/4OMV+ACWY as the third vaccination, actually received Tdap as the third vaccination and was included in 2ABCWYqOMV group for the safety analysis.	From Day 1 to Day 7 after vaccination	Yes
Secondary	Numbers of Subjects With Other Unsolicited AEs	Unsolicited AEs were collected from Day 8 After vaccination Through Study Termination. One subject initially randomized to group 3ABCWYqOMV and supposed to receive rMenB+1/4OMV+ACWY as the third vaccination, actually received Tdap as the third vaccination and was included in 2ABCWYqOMV group for the safety analysis.	Day 8 After vaccination Through Study Termination, up to 6 months	Yes
Secondary	Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) After Vaccination	Solicited local and systemic AEs were collected daily for 7 days (day 1 through day 7) after vaccination. One subject initially randomized to group 3ABCWYqOMV and supposed to receive rMenB+1/4OMV+ACWY as the third vaccination, actually received Tdap as the third vaccination and was included in 2ABCWYqOMV group for the safety analysis.	From Day 1 to Day 7 after vaccination	Yes