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: pactr.samrc.ac.za
Trial no.: PACTR201610001796177 Date of Approval: 27/09/2016
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title PRIMALVAC
Official scientific title Phase Ia/Ib, randomized, double blinded, dose escalation trial to evaluate the safety and immunogenicity of three vaccinations with the recombinant VAR2CSA protein, a gestational malaria candidate vaccine (PRIMVAC vaccine), formulated with Alhydrogel ® or GLA-SE as adjuvants in healthy adults: European malaria-naïve and African living in malaria-endemic region
Brief summary describing the background and objectives of the trial Malaria can be prevented, diagnosed and treated with a combination of available tools from impregnated and long-lasting bed nets, indoor spraying, rapid diagnostics, to the new Artemisinin based Combination Therapy (ACT). However, despite of all increased global efforts to bring malaria under control by implementing these existing tools in a concerted way, an unacceptable high number of people still suffers and dies from the disease. According to the World Health Organization (WHO) in 2013, 3.3 billion people were at risk worldwide, 198 million people suffered from malaria, 584,000 died because of the disease, 91% of deaths occurring in Africa and 85% of them among children under five years of age. Placental Malaria (PM) causes adverse pregnancy outcomes, including anaemia and hypertension in first-time pregnant women, and low birth weight due to premature delivery and foetal growth restriction, which are associated with a higher risk of foetal and neonate morbidity and mortality. Recent estimates suggest that the number of pregnancies exposed to any species of malaria infection worldwide every year is higher than previously estimated. However, for stable P. falciparum transmission areas of sub-Saharan Africa, the figure of approximately 25 million pregnancies at risk of infection annually remains the same. Calculations indicate that 200,000 ¿ 360,000 foetal and infant deaths and at least 10,000 maternal deaths may be attributable to PM every year, representing a major mortality risk. Therefore, vaccination to prevent PM could be designed to protect the mother, foetus or newborn. A PM vaccine would save hundred thousand lives a year. This project aims to developing a vaccine to prevent PM and to assess its safety and explore its immunogenicity in a first-in-human phase I trial and a translational research approach.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) PRIMALVAC
Disease(s) or condition(s) being studied Infections and Infestations,placental malaria, pregnancy associated malaria
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 18/01/2016
Actual trial start date 25/01/2016
Anticipated date of last follow up 30/04/2018
Actual Last follow-up date
Anticipated target sample size (number of participants) 68
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
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 Simple randomisation using a radomisation table created by a computer software program Central randomisation by eCRF Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group PRIMVAC-Alhydrogel 50 µg 3 times one shot vaccination with PRIMVAC vaccine and Alhydrogel adjuvant 16
Control Group NaCl vaccination 3 times one shot vaccination with NaCl 10 Placebo
Experimental Group PRIMVAC Alhydrogel 20 µg 3 times one shot vaccination with PRIMVAC vaccine 20 µg and Alhydrogel adjuvant 3
Experimental Group PRIMVAC GLA-SE 20 µg 3 times one shot vaccination with PRIMVAC vaccine 20µg and GLA-SE adjuvant 3
Experimental Group PRIMVAC-GLA-SE 50 µg 3 times one shot vaccination with PRIMVAC vaccine 50 µg and GLA-SE adjuvant 16
Experimental Group PRIMVAC GLA-SE 100 g 3 times one shot vaccination with PRIMVAC vaccine 100 µg and GLA-SE adjuvant 10
Experimental Group PRIMVAC Alhydrogel 100 µg 3 times one shot vaccination with PRIMVAC vaccine 100 µg and Alhydrogel adjuvant 10
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Written informed consent (must be obtained prior initiation of any study related intervention) ¿ Nulligest Female of age ¿18 years to ¿35 years ¿ Healthy as a result of review of medical history and/or l clinical examination at the time of screening and clinical judgment of the investigator ¿ Available for the duration of the trial (15 months) ¿ Willingness to use reliable contraceptive methods such as: birth control pills or birth control patches or vaginal ring, diaphragm, IUD (intrauterine device), condom, progestin implant or injection, or surgical sterilization (hysterectomy, bilateral oophorectomy, tubal ligation) prior to enrollment at V0 and up to 4 weeks after last vaccination (V6) ¿ Pregnancy ongoing as determined by a positive urinary test ¿ Intention to become pregnant during the trial ¿ Volunteers who are not able to understand and to follow all required study procedures for the whole period of the study in the opinion of the investigator. ¿ Volunteers with history of any illness that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the volunteers due to participation in the study. ¿ Volunteers participating in any clinical study with another investigational product 28 days prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study. ¿ History of psychiatric condition that may affect participation in the study (i.e. depression, anti-depressant treatment) ¿ Prior receipt of an investigational malaria vaccine or any other investigational vaccine likely to impact on interpretation of the study data based on investigator¿s judgment. PRIMALVAC 44/159 Version V2.0_ 17-11-2015 ¿ Volunteer has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months. ¿ History of allergic disease or reactions likely to be exacerbated by any component of the vaccine ¿ History of a serious adverse reaction to any vaccine, including Guillain-Barre syndrome. ¿ Administration or planned administration of a vaccine or gammaglobulin not foreseen by the clinical study protocol within 30 days prior to the first immunization and up to 4 weeks after the last immunization. ¿ Volunteers with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time. ¿ Administration of immunoglobulins and/or any blood products within the three months preceding the inclusion. ¿ Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 3 months (inhaled and topical steroids are allowed) ¿ Seropositive for hepatitis B virus surface antigen (HBsAg) ¿ Seropositive for hepatitis C virus (antibodies to HCV) ¿ Seropositive for human immunodeficiency virus (antibodies to HIV 1-2) ¿ Any other serious chronic illness requiring hospital specialist supervision. ¿ Any clinically significant abnormal finding on screening biochemistry or hematology blood tests or urinalysis ¿ Symptoms, physical signs or laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, cutaneous, immunodeficiency, psychiatric and other conditions, which could interfere with the interpretation of the study results or compromise the health of the volunteers. 18 Year(s) 35 Year(s) Female
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 07/09/2016 CERS
Ethics Committee Address
Street address City Postal code Country
03 BP 7009 Burkina Faso 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 30/10/2015 CPP IDF III
Ethics Committee Address
Street address City Postal code Country
Hôpital Tarnier-Cochin - 89 rue d'Assas Paris 75006 France
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 07/09/2016 CERS
Ethics Committee Address
Street address City Postal code Country
Ouagadougou 03 03 BP 7009 Burkina Faso
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Primary safety endpoint: proportion of volunteers per cohort and arm reporting any Grade 3 or higher clinical or laboratory ARI by the site investigator and persisting at Grade 3 for > 48 hours between D0 and D35. D0 D7 D28 D35
Secondary Outcome Secondary safety endpoints: number, nature and timing of any SAEFI for the entire duration of the study during the entire study
Secondary Outcome Secondary safety endpoints: number, nature and timing of any: AEFI measured until 1 month post-dose 3 (M3) M3
Secondary Outcome Secondary safety endpoints: number, nature and timing of any: AEFI measured between M3 and the end of the study (phase Ia only; cohorts A and B) between M3 and the end of the study (volunteers included in cohort Ia only in France)
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
CIC 1417 Cochin-Pasteur Bâtiment Lavoisier, RDC, Hôpital Cochin, 27 rue du Fg St Jacques Paris Cedex 14 75279 France
CNRFP 01 BP 2208 Ouagadougou Burkina Faso
FUNDING SOURCES
Name of source Street address City Postal code Country
BMBF Kappelle Ufer 1 ¿ Margaret Steffin ¿ Strabe 11 Berlin 10117 Germany
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor INSERM 8 rue de la Croix Jarry Paris 75013 France Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
EVI UniversitätsKlinikum Heidelberg, Voßstraße 2, Geb. 4040 Heidelberg 69115 Germany
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator LAUNAY Odile odile.launay@aphp.fr +33 1 58 41 28 60 CIC Cochin Pasteur (CIC 1417) Bâtiment Lavoisier Groupe Hospitalier Cochin/Broca/Hôtel Dieu 27 rue du Faubourg St Jacques
City Postal code Country Position/Affiliation
Paris 75014 France French PI
Role Name Email Phone Street address
Principal Investigator SIRIMA Sodiomon Bienvenu s.sirima.cnlp@fasonet.bf + 226 25 30 52 20 CNRFP
City Postal code Country Position/Affiliation
Ouagadougou 01 BP 2208 Burkina Faso Burkinabe PI
Role Name Email Phone Street address
Public Enquiries GUEGUEN Sonia sonia.gueguen@inserm.fr +33 1 44 23 61 05 8 rue de la Croix Jarry
City Postal code Country Position/Affiliation
Paris 75013 France Deputy Director of Inserm Clinical Research Department
Role Name Email Phone Street address
Scientific Enquiries GAMAIN Benoît benoit.gamain@inserm.fr +33 1 44 49 31 47 Institut National de Transfusion Sanguine UMR-S 1134, Inserm/Université Paris Diderot 6 Rue Alexandre Cabanel
City Postal code Country Position/Affiliation
Paris 75015 France Scientific Responsible
REPORTING
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URL Results Available Results Summary Result Posting Date First Journal Publication Date
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Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information