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Trial record 3 of 26 for:    RTS,S/AS01

Seasonal Malaria Vaccination (RTS,S/AS01) and Seasonal Malaria Chemoprevention (SP/AQ) (RTSS-SMC)

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ClinicalTrials.gov Identifier: NCT03143218
Recruitment Status : Completed
First Posted : May 8, 2017
Last Update Posted : October 19, 2020
Sponsor:
Collaborators:
Malaria Research and Training Center, Bamako, Mali
Institut de Recherche en Sciences de la Sante, Burkina Faso
Information provided by (Responsible Party):
Brian Greenwood, London School of Hygiene and Tropical Medicine

Brief Summary:
A double-blind, individual randomised trial will be undertaken in 6000 children under the age of five years living in areas of Burkina Faso or Mali where the transmission of malaria is intense and highly seasonal to determine whether the malaria vaccine RTS,S/AS01 is (a) as effective as SMC with SP + AQ in preventing clinical malaria (b) provides additional, useful protection when given together with SMC. The primary trial end-point will be the incidence of clinical episodes of malaria detected by passive case detection.

Condition or disease Intervention/treatment Phase
Malaria,Falciparum Children, Only Biological: RABIPUR® Biological: RTS,S/AS01 Drug: SMC with SP+AQ Drug: SMC placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5920 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

A double-blind, individually randomised trial to compare the incidence of clinical episodes of malaria across three study arms:

  1. Seasonal vaccination with the malaria vaccine RTS,S/AS01
  2. Seasonal malaria chemoprevention with SP/AQ
  3. Combination of these two interventions
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: A Phase IIIB Comparative Trial of Seasonal Vaccination With the Malaria Vaccine RTS,S/AS01, Seasonal Malaria Chemoprevention and of the Two Interventions Combined
Actual Study Start Date : April 17, 2017
Actual Primary Completion Date : June 30, 2020
Actual Study Completion Date : June 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Active Comparator: SMC with SP+AQ
Administration of RABIPUR® in Year 1 and Hepatitis A vaccine in Year 2 and 3, followed by 4 cycles of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1,2 and 3.
Biological: RABIPUR®
Year 1 (2017) Three doses of rabies vaccine (April, May, June) Year 2 and 3 (2018/19) One dose of Hepatitis A vaccine (June)

Drug: SMC with SP+AQ
Year 1, 2 and 3(2017/18/19) Four cycles of SMC (SP+AQ) during the malaria transmission season One cycle of SMC for children above one year of age consisting of sulphadoxine - pyrimethamin (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3. Infants will receive half of these doses.

Active Comparator: RTS,S/AS01
Administration of the malaria vaccine RTS,S/AS01 followed by 4 cycles of SMC with placebo in Year 1,2 and 3.
Biological: RTS,S/AS01
Year 1 (2017) Three doses of RTSS/AS01 (April, May, June) Year 2 and 3 (2018/19) One booster dose of RTSS/AS01 (June)

Drug: SMC placebo
Year 1, 2 and 3(2017/18/19) Four cycles of SMC placebo during the malaria transmission season

Active Comparator: RTS,S/AS01 PLUS SMC with SP+AQ
Administration of the malaria vaccine RTS,S/AS01 followed by 4 cycles of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1,2 and 3.
Biological: RTS,S/AS01
Year 1 (2017) Three doses of RTSS/AS01 (April, May, June) Year 2 and 3 (2018/19) One booster dose of RTSS/AS01 (June)

Drug: SMC with SP+AQ
Year 1, 2 and 3(2017/18/19) Four cycles of SMC (SP+AQ) during the malaria transmission season One cycle of SMC for children above one year of age consisting of sulphadoxine - pyrimethamin (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3. Infants will receive half of these doses.




Primary Outcome Measures :
  1. Incidence of clinical episodes of malaria [ Time Frame: Passive surveillance of clinical episodes of malaria within the study area starting from the date of the first dose of study vaccines (April/May 2017) until 31st March 2020. ]
    Passive surveillance to detect episode of fever (temperature > 37.5 C), or a history of fever within the past 48 hours, that is severe enough to require treatment at a health centre and which is accompanied by a positive blood film with a parasite density of 5,000 per µl or more


Secondary Outcome Measures :
  1. Clinical episodes of uncomplicated febrile illness [ Time Frame: Passive surveillance in all health centers within the study area, active surveillance in a sub set of study children starting July 2017 till April 2020. ]
    Passive and active surveillance to detect cases with temperature > 37.5o C), or a history of fever within the past 48 hours, with a positive blood film (any level of asexual parasitaemia) or a positive rapid diagnostic test (RDT) for malaria

  2. Hospital admissions with malaria, including severe malaria [ Time Frame: Through study completion (30 months), each child admitted in a study hospital will be treated and monitored until complete cure or death (a period of 3 years). Documentation of each hospital admission according to ICH-GCP. ]
    Hospital admissions with malaria, including cases of severe malaria which meet WHO criteria for a diagnosis of severe malaria.

  3. Prevalence of malaria infection not severe enough to warrant a clinic visit [ Time Frame: Weekly home visits through study completion from July 2017 - April 2020 to screen study children for malaria. ]
    Active surveillance of malaria at household level to assess the prevalence of malaria infection not severe enough to warrant a clinic visit detected in a subset of randomly selected children.

  4. Prevalence of malaria parasitaemia, including gametocytaemia and the prevalence of moderate and severe anemia and malnutrition [ Time Frame: Blood sample collection during 2-week cross sectional survey at the end of each malaria transmission season. ]
    The prevalence of malaria parasitaemia, including gametocytaemia, moderate and severe anaemia and malnutrition at the end of the malaria transmission season

  5. Serious adverse events (SAEs) [ Time Frame: Through study completion (for 30 months), each SAE will be treated and documented according to ICH-GCP. ]
    Serious adverse events (SAEs), including any deaths, occurring at any time during the study with special reference to any cases of meningitis and cerebral malaria (WHO case definition)

  6. Immune response to the vaccine (anti-CSP antibody concentrations) [ Time Frame: Blood sample collection prior to 1st dose of vaccine and 1 month after 3rd dose of the primary series of vaccination. In years 2 and 3 blood will be collected before the booster dose and 1 month after administration of the 4th (and 5th) vaccine dose. ]
    After priming and after each booster dose, determined in a sub-sample of children

  7. Drug resistance to SP and AQ [ Time Frame: Blood sample collection during the 2-week cross sectional survey conducted at the end of malaria transmission season in 2019. ]
    The presence of molecular markers of resistance to SP and AQ in parasite positive samples

  8. Prevalence of malaria parasitaemia in school aged children [ Time Frame: Blood sample collection during the 2-week cross sectional survey at the end of the malaria transmission season in Year 2 and 3 (November 2018/19). ]
    The prevalence of malaria parasitaemia at the end of the malaria transmission season in school-age children resident in the study areas, to determine overall malaria transmission

  9. SP+AQ drug sensitivity [ Time Frame: Children with asymptomatic malaria parasitaemia identified during the final cross-sectional survey (November 2019), treated with a full course of SP+AQ over 3 days and followed for 28 days. ]
    The 28-day treatment outcome in children with asymptomatic malaria parasitaemia treated with SP+AQ.


Other Outcome Measures:
  1. Acceptability of RTS,S and SMC [ Time Frame: Data collection in Year 3 ]
    The acceptability of the two interventions (separately and combined) to the health care deliverers and to the study communities (standardized questionnaires)

  2. Feasibility of introducing two malaria control strategies simultaneously [ Time Frame: Data collection in Year 3 ]
    The feasibility of introducing two malaria control strategies simultaneously from the health system perspective (structured observations and interviews with health system officials)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   5 Months to 17 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The child is a permanent resident of the study area and likely to remain a resident for the duration of the trial
  • The child is 5 - 17 months of age at the time of first vaccination
  • A parent or legally recognised guardian provides informed consent for the child to join the trial

Exclusion Criteria:

  • The child is a transient resident in the study area
  • The child is in care
  • The age of the child is outside the stipulated range
  • The child has a history of an adverse reaction to SP or AQ
  • The child has a serious underlying illness, including known HIV infection, unless this is well controlled by treatment, or severe malnutrition (weight for age or mid arm circumference Z scores < 3 SD)
  • The child is known to have an immune deficiency disease or is receiving an immunosuppressive drug
  • The child has previously received a malaria vaccine.
  • The child is enrolled in another malaria intervention trial
  • The parents or guardians do not provide informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03143218


Locations
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Burkina Faso
Institut de Recherche en Sciences de la Santé, Direction Régionale de l'Ouest
Ouagadougou, Burkina Faso
Mali
Malaria Research & Training Center
Bamako, Mali
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
Malaria Research and Training Center, Bamako, Mali
Institut de Recherche en Sciences de la Sante, Burkina Faso
Investigators
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Principal Investigator: Alassane Dicko, Professor Malaria Research & Training Center, Bamako
Study Director: Ogobara Doumbo, Professor Malaria Research & Training Center, Bamako
Study Director: Jean Bosco Ouedraogo, Professor Institut de Recherche en Sciences de la Santé, Direction Régionale de l'Ouest (IRSS-DRO)
Publications:
Neafsey DE, Juraska M, Bedford T, Benkeser D, Valim C, Griggs A, Lievens M, Abdulla S, Adjei S, Agbenyega T, Agnandji ST, Aide P, Anderson S, Ansong D, Aponte JJ, Asante KP, Bejon P, Birkett AJ, Bruls M, Connolly KM, D'Alessandro U, Dobaño C, Gesase S, Greenwood B, Grimsby J, Tinto H, Hamel MJ, Hoffman I, Kamthunzi P, Kariuki S, Kremsner PG, Leach A, Lell B, Lennon NJ, Lusingu J, Marsh K, Martinson F, Molel JT, Moss EL, Njuguna P, Ockenhouse CF, Ogutu BR, Otieno W, Otieno L, Otieno K, Owusu-Agyei S, Park DJ, Pellé K, Robbins D, Russ C, Ryan EM, Sacarlal J, Sogoloff B, Sorgho H, Tanner M, Theander T, Valea I, Volkman SK, Yu Q, Lapierre D, Birren BW, Gilbert PB, Wirth DF. Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine. N Engl J Med. 2015 Nov 19;373(21):2025-2037. doi: 10.1056/NEJMoa1505819. Epub 2015 Oct 21.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Brian Greenwood, Professor, London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT03143218    
Other Study ID Numbers: ITDCZJ29 - Greenwood
First Posted: May 8, 2017    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data will be made available through the LSHTM Data Compass system

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Brian Greenwood, London School of Hygiene and Tropical Medicine:
Malaria
Seasonal vaccination
Seasonal chemoprevention
Additional relevant MeSH terms:
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Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Infections
Vector Borne Diseases