Clinical trial NCT00262002: Study of the Safety and Immune Response of a Meningococcal Vaccine Administered to Healthy Infants
Official title: A Phase II, Randomized, Open Label, Controlled, Multicenter Study to Evaluate the Safety, Immunogenicity and Induction of Immunological Memory After Two or Three Doses of Novartis (Formerly Chiron) Meningococcal ACWY Conjugate Vaccine Administered to Healthy Infants at 2, 3, 4 or 2, 4, 6 Months of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prevention of Meningococcal Disease
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Novartis
First posted: 2005-12-06
Enrollment: 601
Sex: ALL
Minimum age (years): 2
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the safety, immunogenicity and induction of immune memory after two or three doses of Novartis (Formerly Chiron) Meningococcal ACWY Conjugate Vaccine administered to healthy infants.


Eligibility criteria: Inclusion Criteria

Individuals eligible for enrollment in this study were male, and female infants:

* Who were healthy 2-month old infants (55-89 days, inclusive) born after full term pregnancy with an estimated gestational age ≥ 37 weeks, and a birth weight ≥ 2.5 kg;
* For whom a parent/legal guardian has given written informed consent after the nature of the study has been explained;
* Who were available for all the visits scheduled in the study;
* Who were in good health as determined by:

  * Medical history;
  * Physical examination;
  * Clinical judgment of the investigator.

Exclusion Criteria

Ineligible for the study were infants:

* Whose parents/legal guardians were unwilling, or unable to give written informed consent for the subject to participate in the study;
* Who previously received any meningococcal vaccine;
* Who received prior vaccination with D, T, P (acellular, or whole cell), IPV, or OPV, HBV, H influenzae type b (Hib), or Pneumococcus;
* Who had a previously ascertained or suspected disease caused by N meningitidis, C diphtheriae, C tetani, Poliovirus, Hepatitis B, Hib, Pneumococcus, or B pertussis (history of laboratory-confirmed or clinical condition of spasmodic cough for a period ≥ 2 weeks associated with apnea or whooping cough);
* Who had household contact with and/or intimate exposure to an individual with laboratory-confirmed N meningitis (serogroups A, C, W-135, or Y), B pertussis, Hib, C diphtheriae, Polio, or pneumococcal infection since birth;
* Who had a history of any anaphylactic shock, asthma, urticaria, or other allergic reaction after previous vaccinations, or known hypersensitivity to any vaccine component;
* Who had experienced significant acute or chronic infection within the previous 7 days, or fever (≥ 38.0°C) within the previous 3 days;
* Who had any present, or suspected serious, acute (e.g., leukemia, lymphomas), or chronic disease (e.g., with signs of cardiac, renal failure, or severe malnutrition, or insulin-dependent diabetes); or progressive neurological disease; or a genetic anomaly or known cytogenic disorders (e.g., Downs syndrome);
* Who had a known or suspected autoimmune disease or impairment /alteration of immune function resulting from (for example):

  * receipt of any immunosuppressive therapy since birth;
  * receipt of immunostimulant since birth;
  * receipt of any systemic corticosteroid since birth.
* Who had a suspected or known HIV infection, or HIV-related disease;
* Who had ever received blood, blood products and/or plasma derivatives, or any parenteral immunoglobulin preparation;
* Who had a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time;
* Who had a history of seizure disorder:

  * Febrile seizure;
  * Any other seizure disorder.
* Who had taken systemic antibiotics (either oral or parenteral) within the previous 14 days (EXCEPTION: subjects who received an oral or parenteral β-lactam antibiotic \[examples: penicillin, amoxicillin, ceftriaxone, cefuroxime, cephalexin, etc.\] may be enrolled 7 days following the last dose);
* Who with their parents/legal guardians were planning to leave the area of the study site before the end of the study period;
* Who had any condition that, in the opinion of the investigator, might interfere with the evaluation of the study objectives;
* Who had taken any antipyretic medication in the previous 6 hours.

Primary outcomes:
measure: Percentages of Subjects With hSBA Titers ≥ 1:4 Against N. Meningitidis Serogroups A, C, W, and Y Following 3 Doses of MenACWY Ad+ Vaccine
timeFrame: Baseline and at 1 month after the 3 dose primary vaccination series
Secondary outcomes:
measure: Percentages of Subjects With hSBA Titers ≥ 1:8 Against N. Meningitidis Serogroups A, C, W, and Y Following 3 Doses of MenACWY Ad+ Conjugate Vaccine
timeFrame: Baseline and 1 month after the 3 dose primary vaccination series
measure: Geometric Mean hSBA Titers (GMTs) Following 3 Doses of MenACWY Ad+ Conjugate Vaccine
timeFrame: Baseline and 1 month after the 3 dose primary vaccination series
measure: Percentages of Subjects With hSBA Titers ≥ 1:4 or ≥ 1:8 Against N. Meningitidis Serogroups A, C, W, and Y Following 2 Doses of Novartis MenACWY Ad+ or Novartis MenACWY Ad- Conjugate Vaccines
timeFrame: Baseline and 1 month after second vaccination
measure: Geometric Mean hSBA Titer (GMTs) Following 2 Doses of MenACWY Ad+ and MenACWY Ad- Conjugate Vaccines
timeFrame: Baseline and 1 month after second vaccination
measure: Percentages of Subjects With hSBA Titers ≥ 1:4 or ≥ 1:8 Against N. Meningitidis Serogroups A, C, W & Y After a Booster Dose of MenACWY Ad+ or Ad- Vaccine in a Subgroup of Subjects Following 2 or 3 Doses or MenACWY Ad+ or 2 Doses of MenACWY Ad- Vaccine
timeFrame: at 12 months of age and 1 month after booster vaccination
measure: Geometric Mean hSBA Titers (GMT) After a Booster Dose of MenACWY Ad+ or Ad- Vaccine Conjugate in a Subgroup of Subjects Following Either 2 or 3 Doses of MenACWY Ad+ Vaccine or 2 Doses of MenACWY Ad- Conjugate Vaccines
timeFrame: at 12 months of age and 1 month after booster vaccination
measure: Percentages of Subjects With hSBA Titers ≥ 1:4 and ≥ 1:8 Against N. Meningitidis Serogroups A, C, W and Y Following 2 Doses of Novartis MenACWY Ad+ Vaccine, Novartis MenACWY Ad- Vaccine or Novartis Menjugate Vaccine
timeFrame: at 12 months of age
measure: Geometric Mean hSBA Titers (GMTs) After 2 Doses of Novartis MenACWY Ad+ Vaccines, Novartis MenACWY Ad- Vaccine, or Novartis Menjugate Vaccine.
timeFrame: at 12 months of age
measure: Percentages of Subjects With hSBA Titers ≥ 1:4 and ≥ 1:8 Against N. Meningitidis Serogroup A, C, W and Y Following 3 Doses of Novartis MenACWY Ad+ Conjugate Vaccine
timeFrame: at 12 months of age
measure: Geometric Mean hSBA Titers (GMTs) Following 3 Doses of Novartis MenACWY Ad+ Conjugate Vaccine
timeFrame: at 12 months of age
measure: Percentages of Subjects With hSBA Titers ≥ 1:4 or ≥ 1:8 in Subjects Challenged With a Reduced Dose of Licensed Meningococcal ACWY PS Vaccine Following 3 Doses of Novartis MenACWY Ad+ Conjugate Vaccine
timeFrame: before challenge at 12 months of age and 1 month after PS challenge.
measure: Geometric Mean hSBA Titers (GMTs) in Subjects Challenged With a Reduced Dose of Licensed Meningococcal ACWY PS Vaccine Following 3 Doses of Novartis MenACWY Ad+ Conjugate Vaccine
timeFrame: before challenge at 12 months of age and 1 month after PS challenge.
measure: Percentages of Subjects With hSBA Titers ≥ 1:4 or ≥ 1:8 in Subjects Challenged With a Reduced Dose of Licensed Meningococcal ACWY PS Vaccine Following Two Doses of Novartis MenACWY Ad+ or MenACWY Ad- Conjugate Vaccine
timeFrame: Before challenge at 12 months of age and 1 month after PS challenge.
measure: Geometric Mean hSBA Titers (GMTs) in Subjects Challenged With a Reduced Dose of Licensed Meningococcal ACWY PS Vaccine Following Two Doses of Novartis MenACWY Ad+ or MenACWY Ad- Conjugate Vaccine
timeFrame: Before challenge at 12 months of age and 1 month after PS challenge.
measure: Percentages of Subjects With hSBA ≥ 1:4 and ≥ 1:8 of MenACWY Ad+ Conjugate Vaccine
timeFrame: Baseline and 1 month after the 2 or 3 dose primary vaccination series
measure: Percentages of Subjects With hSBA ≥ 1:4 and ≥ 1:8 in Subjects Challenged With a Reduced Dose of a Licensed Meningococcal ACWY PS Vaccine Following 2 or 3 Doses of MenACWY Ad+ Conjugate Vaccine
timeFrame: at 12 months of age and 1 month after PS challenge
measure: Percentages of Subjects With Antibody Response to Routine Vaccines (Hib, Diphtheria, Tetanus, Hepatitis B) When Routine Vaccines Are Given Concomitantly With Novartis MenACWY Ad+ or Novartis MenACWY Ad- Conjugate Vaccines
timeFrame: Baseline and 1 month after the 2 or 3 dose primary vaccination series
measure: ELISA GMT Concentrations for Routine Vaccines (Hib, Diphtheria, Tetanus, Hepatitis B) When Given Concomitantly With Novartis MenACWY Ad+ or Novartis MenACWY Ad- Conjugate Vaccines for Hib, Diphtheria, Tetanus, Hepatitis B
timeFrame: Baseline and 1 month after the 2 or 3 dose primary vaccination series
measure: Percentages of Subjects With hSBA ≥ 1:4 and ≥ 1:8 Against N. Meningitidis Serogroup C Following 2 Doses of MenACWY Ad+ or Ad- Conjugate Vaccine (Containing 5 μg of MenC Oligosaccharide) or 2 Doses of Menjugate (Containing 10 μg of MenC Oligosaccharide)
timeFrame: Baseline and 1 month after second vaccination
measure: Number of Subjects Reporting Solicited Local and Systemic Adverse Events After 2 or 3 Dose Primary Vaccination Series With MenACWY Ad+ or MenACWY Ad-
timeFrame: 7 days after each vaccination
measure: Number of Subjects Reporting Solicited Local and Systemic Adverse Events After MenACWY Ad+ and MenACWY Ad- Booster or Polysaccharide Challenge Administered at 12 Months of Age
timeFrame: 7 days after vaccination at 12 months of age
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Vaccine Evaluation Center
state: British Columbia
city: Halifax
country: Canada
facility: Clinical Trial Research Center
state: Nova Scotia
city: Oxford
country: United Kingdom
facility: Oxford Vaccine Group
Study officials:
affiliation: Novartis Vaccines & Diagnostics
name: Novartis Vaccines
role: STUDY_DIRECTOR
References:
citation: Snape MD, Perrett KP, Ford KJ, John TM, Pace D, Yu LM, Langley JM, McNeil S, Dull PM, Ceddia F, Anemona A, Halperin SA, Dobson S, Pollard AJ. Immunogenicity of a tetravalent meningococcal glycoconjugate vaccine in infants: a randomized controlled trial. JAMA. 2008 Jan 9;299(2):173-84. doi: 10.1001/jama.2007.29-c.
citation: Perrett KP, Snape MD, Ford KJ, John TM, Yu LM, Langley JM, McNeil S, Dull PM, Ceddia F, Anemona A, Halperin SA, Dobson S, Pollard AJ. Immunogenicity and immune memory of a nonadjuvanted quadrivalent meningococcal glycoconjugate vaccine in infants. Pediatr Infect Dis J. 2009 Mar;28(3):186-93. doi: 10.1097/INF.0b013e31818e037d.