Pan African Clinical Trials Registry South African Medical Research Council, South African Cochrane Centre PO Box 19070, Tygerberg, 7505, South Africa Telephone: +27 21 938 0506 / +27 21 938 0834     Fax: +27 21 938 0836 Email: pactradmin@mrc.ac.za     Website: www.pactr.org Trial no.: PACTR2010060002033537 Date registered: 2010/04/07 TRIAL DESCRIPTION Public title Phase II multi-centre study to evaluate efficacy, safety, and immunogenicity of GMZ2 candidate malaria vaccine in children aged 12 to 60 months Official scientific title A phase II, randomized, controlled, double-blind, multi-centre study to evaluate the efficacy, safety, and immunogenicity of GMZ2 candidate malaria vaccine in Gabonese, Bukinabe, Ghanaian, and Ugandan children aged 12 to 60 months Brief summary describing the background and objectives of the trial GMZ2 candidate malaria vaccine; phase IIb multicentred trial enrolling 1840 children aged 12 - 60 months in Gabon; Burkina Faso; Ghana and Uganda. This trial will primarily assess efficacy of the GMZ2 experimental vaccine and secondarily safety and immunogenicity. Humoral and cellular immune responses(quality and functionality)will be explored. GMZ2 experimental vaccine has successfuly undergone phase I safety testing in adults and children. (clintrial.gov NCT00397449,NCT00424944 & NCT00703066) Type of trial RCT Acronym (If the trial has an acronym then please provide) GMZ2_4_10 Disease(s) or condition(s) being studied Malaria , Purpose of the trial Prevention Anticipated trial start date 2010-07-01 Actual trial start date 2010-11-01 Anticipated date of last follow up 2012-09-30 Actual date of last follow up Anticipated target sample size (number of participants) 1840    Actual target sample size (number of participants) 1849    Recruitment status Closed to recruitment: follow up continuing Secondary Ids Issuing authority/Trial register Links to Secondary ID STUDY DESIGN Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used Parallel: different groups receive different interventions at same time during study Randomised Independent Statistician (LSHTM); Simple randomization using Computer software Sealed opaque envelopes Masking/blinding used INTERVENTIONS Intervention type Intervention name Dose Duration Intervention description Group size Nature of control Experimental group Lyophilized recombinant Lactococcus lactis Hybrid GMZ2 [GLURP+MSP3] Three (3) doses of 100µg administered 28 days apart Day 0, 28 & 56 Intramuscular vaccine 920 Control group Human diploid cell (HDC) rabies vaccine 0.5mls on Day 0, 28 & 56 and booster and cross vaccination of GMZ2 at end of study 24 months Intramuscular injection one month apart 920 Active ELIGIBILITY CRITERIA List inclusion criteria List exclusion criteria Min age Max age Gender 1. Children aged 12 - 60 months inclusive at the time of the first dose 2. Healthy by medical history and physical examination 3. Signed or thumb-printed Informed Consent by guardian/parent. Where guardian/parent cannot sign, a witness will be asked to sign to indicate that the procedures were understood and consent was given. 4. Resident in the study villages during the whole clinical trial period 1. Symptoms, physical signs of disease that could interfere with the interpretation of the clinical trial results or compromise the health of the subjects if they were vaccinated 2. Immunosuppressive therapy (steroids, immune modulators or immune suppressors) within three (3) months prior recruitment. (for corticosteroids, this will mean prednisone, or equivalent, ¿ 0.5 mg/kg/day. Inhaled and topical steroids are allowed.) 3. Cannot be followed for any social, psychological or geographical reasons. 4. Use of any investigational drug or vaccine other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use up to the end of the child¿s participation in this clinical trial. 5. Suspected or known hypersensitivity to any of the vaccine components or to any vaccine. 6. Acute or chronic, clinically significant hepatic or renal functional abnormality. 7. Anaemia associated with clinical signs or symptoms of decompensation or haemoglobin < 7.0 g/dL. 8. Planned administration of a vaccine not foreseen by the trial protocol within 30 days of the first dose of vaccine. An exception, is the receipt of an EPI or licensed vaccine (measles, oral polio, Hib, meningococcal and combined diphtheria/ pertussis/ tetanus vaccines) which may be given 14 days or more before or after vaccination 9. Presence of chronic illness that, in the judgement of the investigator, would interfere with the study outcomes or pose a threat to the participant¿s health. 10. Administration of immunoglobulin and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period 11. History of surgical splenectomy. 12. Severe malnutrition at screening defined as weight for age Z-score less than 3 12 Months 60 Months Both ETHICS APPROVAL Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee Yes 2010/05/20 Comite d'ethique pour la recherche en sante Ethics Committee Address Street address City Postal code Country Centre National de rechereche et de Formation sur le Paludisme (CNRFP), Burkina Faso Ouagadougou BP668 Burkina Faso Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee Yes 2010/05/20 Albert Schweitzer Hospital, MRU Ethics Committee Address Street address City Postal code Country Lambaréné B.P.13901 Gabon Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee No 2010/05/20 Navrongo Health Research Center Institutional Review Board Ethics Committee Address Street address City Postal code Country PO Box 114 Navrongo, Upper East Region Ghana Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee Yes Faculty of Medicine and Ethics committee Ethics Committee Address Street address City Postal code Country Makerere University Kampala PO Box 7072 Uganda OUTCOMES Type of outcome Outcome Timepoint(s) at which outcome measured Primary Outcome Efficacy Primary analysis will be done as soon after 6 months of follow-up have elapsed if at least 330 children have had an episode of malaria. In case the target number is not reached by 12 months, analysis will be carried out at 12 months. Secondary Outcome Efficacy on anemia and severe anemia 6 months after full vaccination (D252) Secondary Outcome safety and reactogenicity monitored Secondary Outcome Efficacy on clinical malaria by other case definitions as soon after 6 months of follow-up have elapsed if at least 330 children have had an episode of malaria. In case the target number is not carried out at 12 months Secondary Outcome EXPLORATORY: Humoral and cellular responses Days 0, 28, 56, 84, 168, 252, 365, 588 and 730 as appropriate Secondary Outcome EXPLORATORY: Functionality of immune responses Days 0 and 84, 252, 365, 730 Secondary Outcome EXPLORATORY: Effect of other infections on immune response and vaccine efficacy Days 0, 28, 56, 84, 168, 252, 365, 588 and 730 as appropriate Secondary Outcome EXPLORATORY: Assess changes in parasite population Days 0, 28, 56, 84, 168, 252, 365, 588 and 730 as appropriate Secondary Outcome EXPLORATORY: Investigate evidence for waning of efficacy Days 0, 28, 56, 84, 168, 252, 365, 588 and 730 as appropriate RECRUITMENT CENTRES Name of recruitment centre Street address City Postal code Country Lambarene Lambarene Gabon Inganga Mayuge Mayuge district, Uganda Uganda Banfora (CNRFP) Banfora, Burkina Faso Burkina Faso Navrongo Health Research Center (NHRC) Navrongo Ghana FUNDING SOURCES Name of source Street address City Postal code Country EDCTP Laan van Nieuw Oost Indië 334 The Hague Netherlands SPONSORS Sponsor level Name Street address City Postal code Country Nature of sponsor Primary Sponsor Statens Serum Intitute 85/117 5 Artillerivej Openhagen DK-2300 Denmark Foundation COLLABORATORS Name Street address City Postal code Country Makarere University PO Box 4687 Kampala Uganda Albert Schweitzer Hospital, Medical Research Unit Box BP 13901 Libreville Gabon MRC Laboratories PO Box 273 Banjul Gambia Projet de Development de Vaccins Anti-Paludique - Centre 01 BP 2208 Ouagadougou 01 oq BP 2208 Burkina Faso CONTACT PEOPLE Role Name Email Phone Fax Public Enquiries Dr Dawit Ejigu daejigu@gmail.com 251911405540 Street address City Postal code Country Position / Affiliation Addis Ababa PO Box 329 Ethiopia Staten Serum Institute Role Name Email Phone Fax Scientific Enquiries Dr Thomas L Richie, MD PhD thomas.richie@med.navy.mil 001 301 319 7584 001 301 319 7545 Street address City Postal code Country Position / Affiliation 503 Robert Grant Ave, Room 3A40 Silver Springs, Maryland 20910 - 7500 United States of America Director, Malaria Program, Navy Component Role Name Email Phone Fax Principal Investigator Dr Sodiomon Bienvenu SIRIMA, BA, MD, PHD s.sirima.cnlp@fasonet.bf +22650324695 +22650305220 Street address City Postal code Country Position / Affiliation Projet de developpment de Vaccins Anti-Paludique, Centre National de Recherche et de Formation sur le Paludisme (PDVAP-CNRFP) 01BP2208 Ougadougou 01BP 2208 Burkina Faso Role Name Email Phone Fax Principal Investigator Dr Saadou Issifou, MD MSC, PhD isaadou2002@yahoo.fr +241 07457813 Street address City Postal code Country Position / Affiliation Albert Schweitzer Hosp, Medical Research Unit Libreville BP 13901 Gabon Role Name Email Phone Fax Principal Investigator Mr Fred Kironde PhD kironde@starcom.co.ug +256 782989930 +256 782989930 Street address City Postal code Country Position / Affiliation PO BOx 4687 Kampala Uganda Role Name Email Phone Fax Principal Investigator Mr Atuguba Frank fatuguba@ navrongo.mimcom.org +23374222380 +23374222320 Street address City Postal code Country Position / Affiliation PO Box 114 Navrongo, Upper East Region Ghana Navrongo Health Research Center