A phase II, observer-blind, randomised, active controlled study to compare the safety, immunogenicity, and induction of immunological memory of a meningococcal A conjugate vaccine, a meningococcal ACYW polysaccharide vaccine and a hib conjugate vaccine, administered in healthy toddlers 12 - 23 months of age

ISRCTN	ISRCTN78147026
DOI	https://doi.org/10.1186/ISRCTN78147026
Secondary identifying numbers	RPC178

Submission date: 20/09/2006
Registration date: 21/09/2006
Last edited: 05/03/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Marie-Pierre Preziosi
Scientific

World Health Organization
20 Avenue Appia
Geneva
CH-1211
Switzerland

Phone	+41 (0)22 791 3744
Email	preziosim@who.int

Prof Samba Sow
Scientific

Centre pour les Vaccins en Développement (CVD)
BP 251
Bamako
-
Mali

Dr Brown Okoko
Scientific

PO Box 273
Banjul, Fajara
-
Gambia

Study information

Study design	Phase II observer-blind randomised active-controlled study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Prevention
Participant information sheet	Not available in web format, please use contact details to request a participant information sheet
Scientific title	A phase II, observer-blind, randomised, active controlled study to compare the safety, immunogenicity, and induction of immunological memory of a meningococcal A conjugate vaccine, a meningococcal ACYW polysaccharide vaccine and a hib conjugate vaccine, administered in healthy toddlers 12 - 23 months of age
Study objectives	The present study is pivotal, designed as a non-inferiority trial to evaluate the immunogenicity and the safety of one dose of 10 µg of PsA-TT vaccine. Immunological memory and persistence of antibodies induced by a single intramuscular injection of the study vaccine will also be evaluated. The immunogenicity will be assessed against that of a licensed meningococcal polysaccharide ACYW vaccine. The three-group design will allow comparison of the PsA-TT vaccine (study vaccine group) safety profile with that of two licensed vaccines: the meningococcal ACYW tetravalent polysaccharide vaccine (Mencevax - reference vaccine group), and the Hib-conjugate vaccine (Hiberix - control vaccine group). The booster study is expected to provide evidence that the PsA-TT conjugate vaccine is able to prime immunological memory. Antibody persistence will be evaluated at eight months (i.e. before the booster dose), one year and two years after the first dose.
Ethics approval(s)	This protocol has been approved by the following institutions: 1. Human Subjects Protection Committee at PATH, USA 2. University of Maryland Baltimore Institutional Review Board (IRB), USA 3. Comité d'Ethique de la Faculté de Médecine, de Pharmacie et d'Odonto-Stomatologie, Mali 4. Medical Research Council Scientific Coordinating Committee, The Gambia 5. Medical Research Council Gambia Government Ethics Committee, The Gambia 6. World Health Organization (WHO) Research Ethics Review Committee
Health condition(s) or problem(s) studied	Meningococcal A disease
Intervention	The intervention is vaccination at day zero of one of the three vaccines: study vaccine, reference vaccine (Mencevax) or control vaccine (Hiberix) , followed by a booster vaccination 32 weeks later with one of the three vaccines, study vaccine, reference vaccine (1/5th of a dose) or control vaccine. Subjects will be randomised in a 1:1:1 ratio.
Intervention type	Biological/Vaccine
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	PsA-TT, Mencevax, Hiberix
Primary outcome measure	The percentage of subjects who show a seroconversion for anti-Meningococcal Polysaccharide A (MenPsA) antibodies, i.e. a four-fold increase in post-immunisation serum titre with respect to pre-immunisation serum titre, at 28 days after a single vaccine dose, as measured by rank Signaling Block Age (rSBA) assay.
Secondary outcome measures	1. The percentage of subjects with local and systemic adverse events, including solicited adverse reactions and events, and Serious Adverse Events (SAEs), as measured at four and 28 days after the primary vaccination (reactogenicity and short-term safety) 2. The percentage of subjects with local and systemic adverse events, including solicited adverse reactions and events, and SAEs, as measured at four and 28 days after the booster vaccination (reactogenicity and short-term safety) 3. The percentage of subjects who show a seroconversion for anti-MenPsA total Immunoglobulin G (IgG), i.e. a two-fold increase in post-immunisation serum concentration with respect to pre-immunisation serum concentration, at 28 days after a single vaccine dose, as measured by the Enzyme-Linked ImmunoadSorbent Assay (ELISA). The percentage of subjects with a four-fold increase in post-immunisation serum concentration with respect to pre-immunisation serum concentration will be also considered
Overall study start date	28/08/2006
Completion date	28/11/2008

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	12 Months
Upper age limit	23 Months
Sex	Both
Target number of participants	600
Key inclusion criteria	1. Age 12 to 23 months of age (both included) 2. Written informed consent obtained from the mother, father, or guardian of the child 3. Free of obvious health problems as established by medical history including physical examination and clinical judgment of the investigator 4. Mother, father, or guardian capable and willing to bring their child or to receive home visits for their child for all follow-up visits 5. Residence in the study area 6. Fully vaccinated according to local Expanded Program on Immunisation (EPI) schedule
Key exclusion criteria	1. Previous vaccination against serogroup A Neisseria meningitidis 2. Known exposure to serogroup A Neisseria meningitidis during the three previous months 3. History of allergic disease or known hypersensitivity to any component of the three study vaccines 4. History of Serious Adverse Reactions (SAR) following administration of vaccines included in the local program of immunization 5. Administration of any other vaccine within 60 days prior to administration of study vaccines or planned vaccination during the first four weeks after the study vaccination 6. Use of any investigational or non-registered drug within 90 days prior to the administration of study vaccines 7. Administration of immunoglobulins and/or any blood products since birth or planned administration during the vaccine period 8. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying agents since birth (including systemic or inhaled corticosteroids, this means prednisone or equivalent, 0.5 mg/kg/day [topical steroids are allowed]) 9. A family history of congenital or hereditary immunodeficiency 10. History of meningitis or seizures or any neurological disorder 11. Major congenital defects or serious chronic illness, including malnutrition (as per investigator's judgment) 12. Acute disease at the time of enrolment (acute disease is defined as the presence of a moderate or severe illness with or without fever) is a temporary exclusion 13. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by medical history, physical examination or laboratory tests, which in the opinion of the investigator, might interfere with the study objectives 14. Any condition or criteria that in the opinion of the investigator might compromise the well being of the subject or the compliance with study procedures or interfere with the outcome of the study 15. Non-residence in the study area or intent to move out within one year
Date of first enrolment	28/08/2006
Date of final enrolment	28/11/2008

Locations

Countries of recruitment

Gambia
Mali
Switzerland

Study participating centre

World Health Organization

Geneva
CH-1211
Switzerland

Sponsor information

Serum Institute of India Limited (SIIL)
Research organisation

212/2, Hadapsar
Pune
411028
India

Website	http://www.seruminstitute.com

Program for Appropriate Technology in Health (PATH)
Research organisation

1455 NW Leary Way
Seattle
WA 98107
United States of America

Website	http://www.path.org

Serum Institute of India (India)
Not defined

Website	http://www.seruminstitute.com/
"ROR"	https://ror.org/04jk2xb11

Funders

Funder type

Charity

Bill and Melinda Gates Foundation
Government organisation / Trusts, charities, foundations (both public and private)

Alternative name(s): Bill & Melinda Gates Foundation, Gates Foundation, BMGF, B&MGF, GF
Location: United States of America

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Peer reviewed?	Patient-facing?
Results article	results	16/06/2011	Yes	No
Results article	results	15/11/2015	Yes	No
Results article	results	15/11/2015	Yes	No
Results article	results	15/11/2015	Yes	No
Results article	results	15/11/2015	Yes	No
Results article	results	15/11/2015	Yes	No
Results article	results	15/11/2015	Yes	No

Editorial Notes

05/03/2019: Internal review.
31/08/2016: Publication references added.

This trial was accepted and approved by the ISRCTN on the 18/09/2006, but assigned an ISRCTN on the 21/09/2006 due to technical reasons. The date of the ISRCTN assignment should be taken as the 18/09/2006.