Christian Loucq

Publications (7)85.83 Total impact

• Article: First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children.

  Selidji Todagbe Agnandji, Bertrand Lell, Solange Solmeheim Soulanoudjingar, José Francisco Fernandes, Béatrice Peggy Abossolo, Cornelia Conzelmann, Barbara Gaelle Nfono Ondo Methogo, Yannick Doucka, Arnaud Flamen, Benjamin Mordmüller, [......], Opokua Ofori-Anyinam, Johan Vekemans, Terrell Carter, Didier Leboulleux, Christian Loucq, Afiya Radford, Barbara Savarese, David Schellenberg, Marla Sillman, Preeti Vansadia
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  ABSTRACT: An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries. From March 2009 through January 2011, we enrolled 15,460 children in two age categories--6 to 12 weeks of age and 5 to 17 months of age--for vaccination with either RTS,S/AS01 or a non-malaria comparator vaccine. The primary end point of the analysis was vaccine efficacy against clinical malaria during the 12 months after vaccination in the first 6000 children 5 to 17 months of age at enrollment who received all three doses of vaccine according to protocol. After 250 children had an episode of severe malaria, we evaluated vaccine efficacy against severe malaria in both age categories. In the 14 months after the first dose of vaccine, the incidence of first episodes of clinical malaria in the first 6000 children in the older age category was 0.32 episodes per person-year in the RTS,S/AS01 group and 0.55 episodes per person-year in the control group, for an efficacy of 50.4% (95% confidence interval [CI], 45.8 to 54.6) in the intention-to-treat population and 55.8% (97.5% CI, 50.6 to 60.4) in the per-protocol population. Vaccine efficacy against severe malaria was 45.1% (95% CI, 23.8 to 60.5) in the intention-to-treat population and 47.3% (95% CI, 22.4 to 64.2) in the per-protocol population. Vaccine efficacy against severe malaria in the combined age categories was 34.8% (95% CI, 16.2 to 49.2) in the per-protocol population during an average follow-up of 11 months. Serious adverse events occurred with a similar frequency in the two study groups. Among children in the older age category, the rate of generalized convulsive seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses (95% CI, 0.62 to 1.64). The RTS,S/AS01 vaccine provided protection against both clinical and severe malaria in African children. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619 .).
  New England Journal of Medicine 11/2011; 365(20):1863-75. · 53.30 Impact Factor
• Source

  Available from: PubMed Central

  Article: Design of a phase III multicenter trial to evaluate the efficacy of the RTS,S/AS01 malaria vaccine in children across diverse transmission settings in Africa.

  Amanda Leach, Johan Vekemans, Marc Lievens, Opokua Ofori-Anyinam, Conor Cahill, Seth Owusu-Agyei, Salim Abdulla, Eusebio Macete, Patricia Njuguna, Barbara Savarese, Christian Loucq, W Ripley Ballou
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  ABSTRACT: GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative are working in partnership to develop a malaria vaccine to protect infants and children living in malaria endemic regions of sub-Saharan Africa, which can be delivered through the Expanded Programme on Immunization. The RTS,S/AS candidate vaccine has been evaluated in multiple phase I/II studies and shown to have a favourable safety profile and to be well-tolerated in both adults and children. This paper details the design of the phase III multicentre efficacy trial of the RTS,S/AS01 malaria vaccine candidate, which is pivotal for licensure and policy decision-making. The phase III trial is a randomized, controlled, multicentre, participant- and observer-blind study on-going in 11 centres associated with different malaria transmission settings in seven countries in sub-Saharan Africa. A minimum of 6,000 children in each of two age categories (6-12 weeks, 5-17 months) have been enrolled. Children were randomized 1:1:1 to one of three study groups: (1) primary vaccination with RTS,S/AS01 and booster dose of RTS,S/AS01; (2) primary vaccination with RTS,S/AS01 and a control vaccine at time of booster; (3) primary vaccination with control vaccine and a control vaccine at time of booster. Primary vaccination comprises three doses at monthly intervals; the booster dose is administered at 18 months post-primary course. Subjects will be followed to study month 32. The co-primary objectives are the evaluation of efficacy over one year post-dose 3 against clinical malaria when primary immunization is delivered at: (1) 6-12 weeks of age, with co-administration of DTPwHepB/Hib antigens and OPV; (2) 5-17 months of age. Secondary objectives include evaluation of vaccine efficacy against severe malaria, anaemia, malaria hospitalization, fatal malaria, all-cause mortality and other serious illnesses including sepsis and pneumonia. Efficacy of the vaccine against clinical malaria under different transmission settings, the evolution of efficacy over time and the potential benefit of a booster will be evaluated. In addition, the effect of RTS,S/AS01 vaccination on growth, and the safety and immunogenicity in HIV-infected and malnourished children will be assessed. Safety of the primary course of immunization and the booster dose will be documented in both age categories. This pivotal phase III study of the RTS,S/AS01 candidate malaria vaccine in African children was designed and implemented by the Clinical Trials Partnership Committee. The study will provide efficacy and safety data to fulfil regulatory requirements, together with data on a broad range of endpoints that will facilitate the evaluation of the public health impact of the vaccine and will aid policy and implementation decisions. Clinicaltrials.gov NCT00866619.
  Malaria Journal 08/2011; 10:224. · 3.19 Impact Factor
• Article: Safety and efficacy of the RTS,S/AS01E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19 month follow-up of a randomised, open-label, phase 2 trial.

  Kwaku Poku Asante, Salim Abdulla, Selidji Agnandji, John Lyimo, Johan Vekemans, Solange Soulanoudjingar, Ruth Owusu, Mwanajaa Shomari, Amanda Leach, Erik Jongert, [......], Marla Sillman, Barbara Savarese, Christian Loucq, Didier Lapierre, Brian Greenwood, Joe Cohen, Peter Kremsner, Seth Owusu-Agyei, Marcel Tanner, Bertrand Lell
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  ABSTRACT: The RTS,S/AS01(E) candidate malaria vaccine is being developed for immunisation of infants in Africa through the expanded programme on immunisation (EPI). 8 month follow-up data have been reported for safety and immunogenicity of RTS,S/AS01(E) when integrated into the EPI. We report extended follow-up to 19 months, including efficacy results. We did a randomised, open-label, phase 2 trial of safety and efficacy of the RTS,S/AS01(E) candidate malaria vaccine given with EPI vaccines between April 30, 2007, and Oct 7, 2009, in Ghana, Tanzania, and Gabon. Eligible children were 6-10 weeks of age at first vaccination, without serious acute or chronic illness. All children received the EPI diphtheria, tetanus, pertussis (inactivated whole-cell), and hepatitis-B vaccines, Haemophilus influenzae type b vaccine, and oral polio vaccine at study months 0, 1, and 2, and measles vaccine and yellow fever vaccines at study month 7. Participants were randomly assigned (1:1:1) to receive three doses of RTS,S/AS01(E) at 6, 10, and 14 weeks (0, 1, 2 month schedule) or at 6 weeks, 10 weeks, and 9 months (0, 2, 7 month schedule) or placebo. Randomisation was according to a predefined block list with a computer-generated randomisation code. Detection of serious adverse events and malaria was by passive case detection. Antibodies against Plasmodium falciparum circumsporozoite protein and HBsAg were monitored for 19 months. This study is registered with ClinicalTrials.gov, number NCT00436007. 511 children were enrolled. Serious adverse events occurred in 57 participants in the RTS,S/AS01(E) 0, 1, 2 month group (34%, 95% CI 27-41), 47 in the 0, 1, 7 month group (28%, 21-35), and 49 (29%, 22-36) in the control group; none were judged to be related to study vaccination. At month 19, anticircumsporozoite immune responses were significantly higher in the RTS,S/AS01(E) groups than in the control group. Vaccine efficacy for the 0, 1, 2 month schedule (2 weeks after dose three to month 19, site-adjusted according-to-protocol analysis) was 53% (95% CI 26-70; p=0·0012) against first malaria episodes and 59% (36-74; p=0·0001) against all malaria episodes. For the entire study period, (total vaccinated cohort) vaccine efficacy against all malaria episodes was higher with the 0, 1, 2 month schedule (57%, 95% CI 33-73; p=0·0002) than with the 0, 1, 7 month schedule (32% CI 16-45; p=0·0003). 1 year after dose three, vaccine efficacy against first malaria episodes was similar for both schedules (0, 1, 2 month group, 61·6% [95% CI 35·6-77·1], p<0·001; 0, 1, 7 month group, 63·8% [40·4-78·0], p<0·001, according-to-protocol cohort). Vaccine efficacy was consistent with the target put forward by the WHO-sponsored malaria vaccine technology roadmap for a first-generation malaria vaccine. The 0, 1, 2 month vaccine schedule has been selected for phase 3 candidate vaccine assessment. Program for Appropriate Technology in Health Malaria Vaccine Initiative; GlaxoSmithKline Biologicals.
  The Lancet Infectious Diseases 07/2011; 11(10):741-9. · 17.39 Impact Factor
• Article: Four year immunogenicity of the RTS,S/AS02(A) malaria vaccine in Mozambican children during a phase IIb trial.

  Pedro Aide, Carlota Dobaño, Jahit Sacarlal, John J Aponte, Inácio Mandomando, Caterina Guinovart, Quique Bassat, Montse Renom, Laura Puyol, Eusebio Macete, Esperanza Herreros, Amanda Leach, Marie-Claude Dubois, Marie-Ange Demoitie, Marc Lievens, Johan Vekemans, Christian Loucq, W Ripley Ballou, Joe Cohen, Pedro L Alonso
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  ABSTRACT: Previous studies with the malaria vaccine RTS,S/AS02(A) in young children in a malaria endemic area of Mozambique have shown it to have a promising safety profile and to reduce the risk of Plasmodium falciparum infection and disease. In this study, we assessed the antibody responses to the P. falciparum and hepatitis B components of the RTS,S/AS02(A) vaccine over a 45 months surveillance period in a large phase IIb trial which included 2022 children aged 1-4 years at recruitment. The RTS,S/AS02(A) vaccine induced high anti-circumsporozoite antibody levels with at least 96% of children remaining seropositive during the entire follow-up period. IgG titers decayed over the first 6 months of follow-up to about 25% of the initial level, but still remained 30-fold higher until month 45 compared to controls. Children with higher levels of naturally acquired immunity at baseline, assessed by blood stage indirect fluorescent antibody test, had slightly higher anti-circumsporozoite levels, after adjusting for the effect of age. The RTS,S/AS02(A) vaccine also induced high levels of anti-hepatitis B surface antigen antibodies (seroprotection >97%). RTS,S/AS02(A) vaccine is immunogenic and induces long-lasting anti-circumsporozoite antibodies, persisting at least 42 months after immunization. These antibodies may play a role in protection against malaria.
  Vaccine 03/2011; 29(35):6059-67. · 3.77 Impact Factor
• Source

  Available from: Jahit Sacarlal

  Article: Safety, immunogenicity and duration of protection of the RTS,S/AS02(D) malaria vaccine: one year follow-up of a randomized controlled phase I/IIb trial.

  Pedro Aide, John J Aponte, Montse Renom, Tacilta Nhampossa, Jahit Sacarlal, Inacio Mandomando, Quique Bassat, Maria Nélia Manaca, Amanda Leach, Marc Lievens, Johan Vekemans, Marie-Claude Dubois, Christian Loucq, W Ripley Ballou, Joe Cohen, Pedro L Alonso
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  ABSTRACT: The RTS,S/AS02(D) vaccine has been shown to have a promising safety profile, to be immunogenic and to confer protection against malaria in children and infants. We did a randomized, controlled, phase I/IIb trial of RTS,S/AS02(D) given at 10, 14 and 18 weeks of age staggered with routine immunization vaccines in 214 Mozambican infants. The study was double-blind until the young child completed 6 months of follow-up over which period vaccine efficacy against new Plasmodium falciparum infections was estimated at 65.9% (95% CI 42.6-79.8, p<0.0001). We now report safety, immunogenicity and estimated efficacy against clinical malaria up to 14 months after study start. Vaccine efficacy was assessed using Cox regression models. The frequency of serious adverse events was 32.7% in the RTS,S/AS02(D) and 31.8% in the control group. The geometric mean titers of anti-circumsporozoite antibodies declined from 199.9 to 7.3 EU/mL from one to 12 months post dose three of RTS,S/AS02(D), remaining 15-fold higher than in the control group. Vaccine efficacy against clinical malaria was 33% (95% CI: -4.3-56.9, p = 0.076) over 14 months of follow-up. The hazard rate of disease per 2-fold increase in anti-CS titters was reduced by 84% (95% CI 35.1-88.2, p = 0.003). The RTS,S/AS02(D) malaria vaccine administered to young infants has a good safety profile and remains efficacious over 14 months. A strong association between anti-CS antibodies and risk of clinical malaria has been described for the first time. The results also suggest a decrease of both anti-CS antibodies and vaccine efficacy over time. ClinicalTrials.gov NCT00197028.
  PLoS ONE 01/2010; 5(11):e13838. · 4.09 Impact Factor
• Source

  Available from: Jahit Sacarlal

  Article: Insights into long-lasting protection induced by RTS,S/AS02A malaria vaccine: further results from a phase IIb trial in Mozambican children.

  Caterina Guinovart, John J Aponte, Jahit Sacarlal, Pedro Aide, Amanda Leach, Quique Bassat, Eusébio Macete, Carlota Dobaño, Marc Lievens, Christian Loucq, W Ripley Ballou, Joe Cohen, Pedro L Alonso
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  ABSTRACT: The pre-erythrocytic malaria vaccine RTS,S/AS02A has shown to confer protection against clinical malaria for at least 21 months in a trial in Mozambican children. Efficacy varied between different endpoints, such as parasitaemia or clinical malaria; however the underlying mechanisms that determine efficacy and its duration remain unknown. We performed a new, exploratory analysis to explore differences in the duration of protection among participants to better understand the protection afforded by RTS,S. The study was a Phase IIb double-blind, randomized controlled trial in 2022 children aged 1 to 4 years. The trial was designed with two cohorts to estimate vaccine efficacy against two different endpoints: clinical malaria (cohort 1) and infection (cohort 2). Participants were randomly allocated to receive three doses of RTS,S/AS02A or control vaccines. We did a retrospective, unplanned sub-analysis of cohort 2 data using information collected for safety through the health facility-based passive case detection system. Vaccine efficacy against clinical malaria was estimated over the first six-month surveillance period (double-blind phase) and over the following 12 months (single-blind phase), and analysis was per-protocol. Adjusted vaccine efficacy against first clinical malaria episodes in cohort 2 was of 35.4% (95% CI 4.5-56.3; p = 0.029) over the double-blind phase and of 9.0% (-30.6-36.6; p = 0.609) during the single-blind phase. Contrary to observations in cohort 1, where efficacy against clinical malaria did not wane over time, in cohort 2 the efficacy decreases with time. We hypothesize that this reduced duration of protection is a result of the early diagnosis and treatment of infections in cohort 2 participants, preventing sufficient exposure to asexual-stage antigens. On the other hand, the long-term protection against clinical disease observed in cohort 1 may be a consequence of a prolonged exposure to low-dose blood-stage asexual parasitaemia. ClinicalTrials.gov NCT00197041.
  PLoS ONE 02/2009; 4(4):e5165. · 4.09 Impact Factor
• Article: Four year immunogenicity of the RTS,S/AS02A malaria vaccine in Mozambican children during a phase IIb trial

  Pedro Aide, Carlota Dobaño, Jahit Sacarlal, John J. Aponte, Inácio Mandomando, Caterina Guinovart, Quique Bassat, Montse Renom, Laura Puyol, Eusebio Macete, Esperanza Herreros, Amanda Leach, Marie-Claude Dubois, Marie-Ange Demoitie, Marc Lievens, Johan Vekemans, Christian Loucq, W. Ripley Ballou, Joe Cohen, Pedro L. Alonso
  [show abstract] [hide abstract]
  ABSTRACT: Previous studies with the malaria vaccine RTS,S/AS02A in young children in a malaria endemic area of Mozambique have shown it to have a promising safety profile and to reduce the risk of Plasmodium falciparum infection and disease.In this study, we assessed the antibody responses to the P. falciparum and hepatitis B components of the RTS,S/AS02A vaccine over a 45 months surveillance period in a large phase IIb trial which included 2022 children aged 1–4 years at recruitment.The RTS,S/AS02A vaccine induced high anti-circumsporozoite antibody levels with at least 96% of children remaining seropositive during the entire follow-up period. IgG titers decayed over the first 6 months of follow-up to about 25% of the initial level, but still remained 30-fold higher until month 45 compared to controls. Children with higher levels of naturally acquired immunity at baseline, assessed by blood stage indirect fluorescent antibody test, had slightly higher anti-circumsporozoite levels, after adjusting for the effect of age.The RTS,S/AS02A vaccine also induced high levels of anti-hepatitis B surface antigen antibodies (seroprotection >97%).RTS,S/AS02A vaccine is immunogenic and induces long-lasting anti-circumsporozoite antibodies, persisting at least 42 months after immunization. These antibodies may play a role in protection against malaria.
  Vaccine.