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Clinical Study of Meningococcal ACYWX Conjugate Vaccine, in 12-16 Month Olds

Primary Purpose

Meningitis, Meningococcal

Status
Completed
Phase
Phase 2
Locations
Mali
Study Type
Interventional
Intervention
Non-adjuvanted study formulation NmCV-5
Adjuvanted study formulation NmCV-5
Menactra
Sponsored by
Serum Institute of India Pvt. Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Meningitis, Meningococcal focused on measuring Neisseria meningitidis, conjugate meningococcal vaccine, meningococcal serogroup X

Eligibility Criteria

12 Months - 16 Months (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Male and female children between 12 months and 16 months old inclusive (minimum 365 days of age and maximum 16 months plus 29 days of age);
  • For whom parent(s)/legal guardian(s) have given written informed consent after the nature of the study has been explained according to local regulatory requirements;
  • Who the investigator believes that their parent(s)/ guardian(s) will be available for all the subject visits and would comply with the requirements of the protocol (e.g., timely reporting of adverse events, availability for study site visits and home visits);
  • Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator.
  • Individuals who completed their local infant EPI schedule through 9 months of age (except MenAfriVac dose). A birth dose of OPV is not required)

Exclusion Criteria:

  • History of any meningococcal vaccine administration.
  • Current or previous, confirmed or suspected disease caused by N. meningitidis.
  • Household contact with and/or intimate exposure to an individual with any laboratory confirmed N. meningitidis infection within 60 days of enrolment.
  • History of severe allergic reactions after previous vaccinations or hypersensitivity to any study vaccine component including tetanus, diphtheria and diphtheria toxoid (CRM197).
  • Acute or chronic, clinically significant pulmonary, cardiovascular, metabolic, neurological, hepatic, or renal functional abnormality, as determined by medical history or physical examination.
  • Any confirmed or suspected condition with impaired/altered function of immune system (immunodeficient or autoimmune conditions).
  • Have any bleeding disorder which is considered as a contraindication to intramuscular injection or blood draw.
  • Severe acute malnutrition.
  • A family history of congenital or hereditary immunodeficiency.
  • History of either hepatitis B or hepatitis C virus infection or human immunodeficiency virus infection.
  • Major congenital defects.
  • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within three months prior to the study vaccination or planned use throughout the study period. (For corticosteroids, this means prednisone, or equivalent, ≥ 0.5 mg/kg per day. Inhaled, intranasal and topical steroids are allowed).
  • Administration of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 3 months or planned use throughout the study period.
  • Administration of any vaccine within 28 days prior to enrolment in the study or planned administration of any vaccine within 14 days before or after any study vaccination.
  • Use of any investigational or non-registered drug or vaccine within 30 days prior to the administration of study vaccines or planned during the study.
  • Malaria infection as confirmed by a Rapid Diagnostic Test.
  • Individuals who are close family members of individuals conducting this study.
  • Have experienced a moderate or severe acute infection and/or fever (defined as temperature ≥ 37.5°C) within 3 days prior to enrolment.
  • Have received systemic antibiotic treatment within 3 days prior to enrolment.
  • Non-residence in the study area or intent to move out within six months.
  • Any condition which, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study

Sites / Locations

  • Centre pour le Développement des Vaccins du Mali, ex-Institut Marchoux, Ministry of Health, BP251

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Adjuvanted study formulation NmCV-5

Non-adjuvanted study formulation NmCV-5

Menactra

Arm Description

Subjects in this arm will receive adjuvanted formulation of polyvalent conjugated vaccine against meningococcal serogroups A,C,Y,W & X. Dose to be administered is 0.5 mL intramuscularly in a two dose series separated by atleast 84 days.

Subjects in this arm will receive non-adjuvanted formulation of polyvalent conjugated vaccine against meningococcal serogroups A,C,Y,W & X. Dose to be administered is 0.5 mL intramuscularly in a two dose series separated by atleast 84 days.

Subjects in this arm will licensed quadrivalent conjugated vaccine against meningococcal serogroups A,C,Y, & W viz. Menactra. Dose to be administered is 0.5 mL intramuscularly in a two dose series separated by atleast 84 days.

Outcomes

Primary Outcome Measures

Severe Solicited Adverse Event
Percentage of subjects with at least one severe solicited AE within 7 days after any study vaccination (Days 0-6 and Days 84-90)

Secondary Outcome Measures

Seroprotective rSBA Titres
Percentage of subjects with rSBA titer ≥ 8 against serogroups A, C, W, Y and X at Visits Day 0 (Baseline), Day 28 (28 days after dose 1), Day 84 (prior to dose 2) and Day 112 (28 days after dose 2)
Long Term Protective rSBA Titres
Percentage of subjects with rSBA titer ≥ 128 against serogroups A, C, W, Y and X at Visits Day 0, Day 28, Day 84 and Day 112
Rise in rSBA Titres
Percentage of subjects with fourfold rise in rSBA titers against serogroups A, C, W, Y and X at Visits Day 28 and Day 112. For subjects with a pre-vaccination rSBA titer < 8, a post-vaccination titer of ≥ 32; For subjects with a pre-vaccination rSBA titer ≥ 8, an increase in rSBA titer of at least 4 times the pre-vaccination titer
Geometric Mean of rSBA Titres
rSBA GMT for serogroups A, C, W, Y and X at Visits Day 0, Day 28, Day 84 and Day 112
Solicited Reactions
Solicited local and systemic AEs reported during the 7 days after each vaccination (Days 0-6 and Days 84-90);
Adverse Events
Unsolicited AEs reported during 28 days after each vaccination (Days 0-27 and Days 84-111);
Other Adverse Events
AEs leading to premature withdrawal during the entire study period;
Serious Adverse Events
SAEs reported during the entire study period

Full Information

First Posted
September 20, 2017
Last Updated
August 10, 2021
Sponsor
Serum Institute of India Pvt. Ltd.
Collaborators
PATH
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1. Study Identification

Unique Protocol Identification Number
NCT03295318
Brief Title
Clinical Study of Meningococcal ACYWX Conjugate Vaccine, in 12-16 Month Olds
Official Title
A Phase 2, Observer-blind, Randomized, Controlled Study to Evaluate the Safety and Immunogenicity of Two Formulations of Investigational Meningococcal Groups ACYWX Conjugate Vaccine, Administered to Healthy Malian Children 12-16 Months of Age
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
November 15, 2017 (Actual)
Primary Completion Date
August 31, 2018 (Actual)
Study Completion Date
August 31, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Serum Institute of India Pvt. Ltd.
Collaborators
PATH

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Out of the 13 identified serogroups of Neisseria meningitidis (Nm) the six serogroups (A, B, C, W, Y and X) are responsible for majority of infections. Presently available vaccines effectively protect against A, B, C, W and Y serogroups; but no vaccine that is protective against serogroup X is available yet. Serum Institute of India Private Limited (SIIPL) has developed a conjugate vaccine against serogroups A, C, Y, W and X (NmCV-5). The first-in-human Phase 1 study was among 60 healthy adults in USA did not show no any safety issues. This phase 2 study is designed to evaluate safety and immunogenicity of the non-adjuvanted and adjuvanted formulations of NmCV-5 in healthy children 12-16 months of age, in comparison with the licensed quadrivalent meningococcal conjugate vaccine (Menactra®). Both vaccines will be administered in two dose schedule 3 months apart. among vaccine-naïve healthy subjects in Mali. Safety will be assessed by collecting solicited reactions till day 7 post each dose whereas adverse events will be collected throughout the study. Each subject will be followed up for 84 days post each vaccine dose. The vaccine immunogenicity will measured using a rabbit complement serum bactericidal activity assay (rSBA).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Meningitis, Meningococcal
Keywords
Neisseria meningitidis, conjugate meningococcal vaccine, meningococcal serogroup X

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Observer blind wherein the pharmacist and other study staff involved in vaccine administration will be aware of the treatment allocation. The other study staff involved in safety assessments will be masked to treatment arm. The laboratory involved in immunogenicity analysis will also be blinded to the treatment allocation.
Allocation
Randomized
Enrollment
375 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Adjuvanted study formulation NmCV-5
Arm Type
Experimental
Arm Description
Subjects in this arm will receive adjuvanted formulation of polyvalent conjugated vaccine against meningococcal serogroups A,C,Y,W & X. Dose to be administered is 0.5 mL intramuscularly in a two dose series separated by atleast 84 days.
Arm Title
Non-adjuvanted study formulation NmCV-5
Arm Type
Experimental
Arm Description
Subjects in this arm will receive non-adjuvanted formulation of polyvalent conjugated vaccine against meningococcal serogroups A,C,Y,W & X. Dose to be administered is 0.5 mL intramuscularly in a two dose series separated by atleast 84 days.
Arm Title
Menactra
Arm Type
Active Comparator
Arm Description
Subjects in this arm will licensed quadrivalent conjugated vaccine against meningococcal serogroups A,C,Y, & W viz. Menactra. Dose to be administered is 0.5 mL intramuscularly in a two dose series separated by atleast 84 days.
Intervention Type
Biological
Intervention Name(s)
Non-adjuvanted study formulation NmCV-5
Other Intervention Name(s)
MenACYWX
Intervention Description
Non-adjuvanted formulation of polyvalent conjugate meningococcal vaccine against serogroups A,C,Y,W&X (NmCV-5) is available as lyophilised powder of polysacchride antigens A&X conjugated to tetanus toxoid and C,Y&W conjugated to CRM protein. The diluent contains Normal Saline. Each antigen content is 5 micrograms per 0.5 mL dose of vaccine.
Intervention Type
Biological
Intervention Name(s)
Adjuvanted study formulation NmCV-5
Other Intervention Name(s)
Adj MenACYWX
Intervention Description
Adjuvanted formulation of polyvalent conjugate meningococcal vaccine against serogroups A,C,Y,W&X (NmCV-5) is available as lyophilised powder of polysacchride antigens A&X conjugated to tetanus toxoid and C,Y&W conjugated to CRM protein. The diluent contains Alum as adjuvant with Normal Saline. Each antigen content is 5 micrograms per 0.5 mL dose of vaccine
Intervention Type
Biological
Intervention Name(s)
Menactra
Other Intervention Name(s)
MenACYW-D
Intervention Description
Menactra is available as ready to used solution containing polysacchride antigens A,C,Y&WX conjugated to diphtheria toxoid. Each antigen content is 4 micrograms per 0.5 mL dose of vaccine.
Primary Outcome Measure Information:
Title
Severe Solicited Adverse Event
Description
Percentage of subjects with at least one severe solicited AE within 7 days after any study vaccination (Days 0-6 and Days 84-90)
Time Frame
7 days post each vaccination
Secondary Outcome Measure Information:
Title
Seroprotective rSBA Titres
Description
Percentage of subjects with rSBA titer ≥ 8 against serogroups A, C, W, Y and X at Visits Day 0 (Baseline), Day 28 (28 days after dose 1), Day 84 (prior to dose 2) and Day 112 (28 days after dose 2)
Time Frame
112 days
Title
Long Term Protective rSBA Titres
Description
Percentage of subjects with rSBA titer ≥ 128 against serogroups A, C, W, Y and X at Visits Day 0, Day 28, Day 84 and Day 112
Time Frame
112 days
Title
Rise in rSBA Titres
Description
Percentage of subjects with fourfold rise in rSBA titers against serogroups A, C, W, Y and X at Visits Day 28 and Day 112. For subjects with a pre-vaccination rSBA titer < 8, a post-vaccination titer of ≥ 32; For subjects with a pre-vaccination rSBA titer ≥ 8, an increase in rSBA titer of at least 4 times the pre-vaccination titer
Time Frame
112 days
Title
Geometric Mean of rSBA Titres
Description
rSBA GMT for serogroups A, C, W, Y and X at Visits Day 0, Day 28, Day 84 and Day 112
Time Frame
112 Days
Title
Solicited Reactions
Description
Solicited local and systemic AEs reported during the 7 days after each vaccination (Days 0-6 and Days 84-90);
Time Frame
7 days post each vaccination
Title
Adverse Events
Description
Unsolicited AEs reported during 28 days after each vaccination (Days 0-27 and Days 84-111);
Time Frame
112 Days
Title
Other Adverse Events
Description
AEs leading to premature withdrawal during the entire study period;
Time Frame
168 Days
Title
Serious Adverse Events
Description
SAEs reported during the entire study period
Time Frame
168 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Months
Maximum Age & Unit of Time
16 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Male and female children between 12 months and 16 months old inclusive (minimum 365 days of age and maximum 16 months plus 29 days of age); For whom parent(s)/legal guardian(s) have given written informed consent after the nature of the study has been explained according to local regulatory requirements; Who the investigator believes that their parent(s)/ guardian(s) will be available for all the subject visits and would comply with the requirements of the protocol (e.g., timely reporting of adverse events, availability for study site visits and home visits); Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator. Individuals who completed their local infant EPI schedule through 9 months of age (except MenAfriVac dose). A birth dose of OPV is not required) Exclusion Criteria: History of any meningococcal vaccine administration. Current or previous, confirmed or suspected disease caused by N. meningitidis. Household contact with and/or intimate exposure to an individual with any laboratory confirmed N. meningitidis infection within 60 days of enrolment. History of severe allergic reactions after previous vaccinations or hypersensitivity to any study vaccine component including tetanus, diphtheria and diphtheria toxoid (CRM197). Acute or chronic, clinically significant pulmonary, cardiovascular, metabolic, neurological, hepatic, or renal functional abnormality, as determined by medical history or physical examination. Any confirmed or suspected condition with impaired/altered function of immune system (immunodeficient or autoimmune conditions). Have any bleeding disorder which is considered as a contraindication to intramuscular injection or blood draw. Severe acute malnutrition. A family history of congenital or hereditary immunodeficiency. History of either hepatitis B or hepatitis C virus infection or human immunodeficiency virus infection. Major congenital defects. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within three months prior to the study vaccination or planned use throughout the study period. (For corticosteroids, this means prednisone, or equivalent, ≥ 0.5 mg/kg per day. Inhaled, intranasal and topical steroids are allowed). Administration of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 3 months or planned use throughout the study period. Administration of any vaccine within 28 days prior to enrolment in the study or planned administration of any vaccine within 14 days before or after any study vaccination. Use of any investigational or non-registered drug or vaccine within 30 days prior to the administration of study vaccines or planned during the study. Malaria infection as confirmed by a Rapid Diagnostic Test. Individuals who are close family members of individuals conducting this study. Have experienced a moderate or severe acute infection and/or fever (defined as temperature ≥ 37.5°C) within 3 days prior to enrolment. Have received systemic antibiotic treatment within 3 days prior to enrolment. Non-residence in the study area or intent to move out within six months. Any condition which, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study
Facility Information:
Facility Name
Centre pour le Développement des Vaccins du Mali, ex-Institut Marchoux, Ministry of Health, BP251
City
Bamako
ZIP/Postal Code
BP251
Country
Mali

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34077644
Citation
Tapia MD, Sow SO, Naficy A, Diallo F, Haidara FC, Chaudhari A, Martellet L, Traore A, Townsend-Payne K, Borrow R, Hosken N, Smolenov I, Pisal SS, LaForce FM, Dhere RM, Kapse D, Tang Y, Alderson MR, Kulkarni PS. Meningococcal Serogroup ACWYX Conjugate Vaccine in Malian Toddlers. N Engl J Med. 2021 Jun 3;384(22):2115-2123. doi: 10.1056/NEJMoa2013615.
Results Reference
derived

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Clinical Study of Meningococcal ACYWX Conjugate Vaccine, in 12-16 Month Olds

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