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

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ClinicalTrials.gov Identifier: NCT04319380
Recruitment Status : Not yet recruiting
First Posted : March 24, 2020
Last Update Posted : March 24, 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):
London School of Hygiene and Tropical Medicine

Brief Summary:
A double-blind, individual randomised trial will be undertaken in children under five years of age living in areas of Burkina Faso or Mali where the transmission of malaria is intense and highly seasonal to determine whether administration of further doses of the malaria vaccine RTS,S/AS01 at the beginning of the malaria transmission until children reach the age of five years 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. This is a two year extension of the current RTS,S/AS01 + SMC trial to continue the trial until the study children reach the age of five years, the current age at which SMC is recommended until.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 4800 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: Seasonal Vaccination With the RTS,S/AS01 Malaria Vaccine Given With or Without Seasonal Malaria Chemoprevention: Extension of a Randomised, Double-blind Phase 3 Trial Until Children Reach the Age of Five Years
Estimated Study Start Date : May 2020
Estimated Primary Completion Date : March 31, 2022
Estimated Study Completion Date : March 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Active Comparator: SMC with SP+AQ
Administration of Tetanus toxoid vaccine followed by 4 rounds of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1 and 2.
Biological: Tetanus toxoid
One dose of tetanus toxoid vaccine (June) in year 1 and year 2.

Drug: SMC with SP+AQ
Year 1 and 2 (2020/21) Four rounds of SMC (SP+AQ) (July, August, September, October). One round of SMC consisting of sulphadoxine - pyrimethamine (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3.

Active Comparator: RTS,S/AS01
Administration of the malaria vaccine RTS,S/AS01 followed by 4 rounds of SMC with placebo in Year 1 and 2.
Biological: RTS,S/AS01
One booster dose of RTSS/AS01 (June) in year 1 and 2.

Drug: SMC placebo
Year 1 and 2 (2020/21) Four rounds of SMC placebo (July, August, September, October)

Active Comparator: RTS,S/AS01 plus SMC with SP+AQ
Administration of the malaria vaccine RTS,S/AS01 followed by 4 rounds of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1 and 2.
Drug: SMC with SP+AQ
Year 1 and 2 (2020/21) Four rounds of SMC (SP+AQ) (July, August, September, October). One round of SMC consisting of sulphadoxine - pyrimethamine (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3.

Biological: RTS,S/AS01
One booster dose of RTSS/AS01 (June) in year 1 and 2.




Primary Outcome Measures :
  1. Incidence of clinical episodes of malaria [ Time Frame: Passive surveillance of clinical episodes of malaria within the study area starting 4 weeks post 6th dose of vaccination (1 July 2020) until 31 March 2022. ]
    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 4 weeks post primary vaccination (1 July 2020) until 31 March 2022. ]
    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, each child admitted in a study hospital will be treated and monitored until complete cure or death (a period of 2 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 1 July 2020 - 31 March 2022 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 (November 2020/21).). ]
    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 2 years), 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 0-7 days before and one month after the booster doses (year 1 and 2). ]
    Anti-CSP antibody concentrations obtained before and after each booster dose, determined in a sub-sample of children.

  7. Prevalence of malaria parasitaemia in school aged children [ Time Frame: Blood sample collection during the 2-week cross sectional survey at the end of each malaria transmission season (November 2020/21). ]
    The prevalence of malaria parasitaemia at the end of each malaria transmission season in school-age children resident in the study areas, to determine overall malaria transmission

  8. Polymorphisms in the P. falciparum CSP [ Time Frame: Blood sample collection from children with clinical episodes of malaria and in children with parasitaemia at the 2-week cross-sectional survey (November 2020/21)). ]
    The prevalence of mutations in the Th2 or Th3 locus of the Plasmodium falciparum csp gene in isolates from children who have received RTS,S/AS01 that differ from those of the isolate used in the preparation of the vaccine

  9. Drug resistance to SP and AQ [ Time Frame: Blood sample collection during the final 2-week cross sectional survey conducted at the end of malaria transmission season (November 2021) ]
    The presence of molecular markers of resistance to SP and AQ in parasite positive samples

  10. SP+AQ drug sensitivity [ Time Frame: Children with asymptomatic malaria parasitaemia identified during the final cross-sectional survey (November 2021), 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.

  11. 'Rebound' malaria [ Time Frame: Passive surveillance of uncomplicated and severe cases of malaria in hospitals and clinics within the study area during the 4 month (July- October) 2021 transmission season. ]
    Incidence of uncomplicated malaria and hospitalisation for severe malaria in study children who have reached the age of five years at the time of the last year of the trial and who are no longer eligible to receive either of the trial interventions


Other Outcome Measures:
  1. Perceptions of acceptability of seasonal RTS,S/AS01 vaccination [ Time Frame: Data collection via in-depth interviews and focus group discussions in Year 1 and Year 2 ]
    Perceptions of acceptability of seasonal RTS,S/AS01 vaccination, in addition to, or as a replacement for SMC to those who receive it, and those who deliver it.

  2. Perceptions of feasibility of seasonal RTS,S/AS01 vaccination [ Time Frame: Data collection via in-depth interviews and focus groups discussions in Year 1 and Year 2 ]
    Perceptions of policy makers and health programme deliverers of the feasibility of introducing seasonal RTS,S/AS01 vaccination into the current health systems, either in addition to, or as a replacement for SMC.



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:   3 Years to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The child had been enrolled in the initial phase of the trial of seasonal vaccination with the RTS,S/AS01 vaccine
  • A parent or legally recognised guardian provides informed consent for the child's inclusion in the extension study
  • 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 under five years of age at the time of enrolment.

Exclusion Criteria:

  • The child has had an allergic reaction to the study drugs or vaccines
  • The child had febrile convulsions on more than one occasion following vaccination
  • The child has developed a serious underlying illness such as severe malnutrition (weight for age or mid arm circumference Z scores < 3 SD) which in view of the investigators might impair the response to vaccination
  • The child has been enrolled in another malaria vaccine or other experimental malaria intervention study

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): NCT04319380


Contacts
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Contact: Daniel Chandramohan, Professor + 442079272322 daniel.chandramohan@lshtm.ac.uk
Contact: Brian Greenwood, Professor + 442072994712 brian.greenwood@lshtm.ac.uk

Locations
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Burkina Faso
Institut de Recherche en Sciences de la Santé
Ouagadougou, Direction Régionale De l'Ouest, Burkina Faso
Contact: Jean Bosco Ouedraogo, Professor         
Mali
Malaria Research & Training Center
Bamako, Mali
Contact: Alassane Dicko, Professor         
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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Study Director: Alassane Dicko, 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)
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Responsible Party: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT04319380    
Other Study ID Numbers: RTS,S + SMC extn
First Posted: March 24, 2020    Key Record Dates
Last Update Posted: March 24, 2020
Last Verified: March 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 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