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

NCT04319380 | Completed Phase 3 Results DMC

• 1 other identifier: RTS,S + SMC extn
• Study Type: interventional
• Target: 5,098
• Locations: 2 countries
• Sites: 2

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.

Conditions

Malaria,Falciparum; Child, Only

Keywords

Malaria; Seasonal vaccination; Seasonal chemoprevention

Outcome Measures

Primary Outcomes (1)

• Incidence of Clinical Episodes of Malaria

  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

  Passive surveillance of clinical episodes of malaria within the study area over 24 months (1 April 2020 until 31 March 2022).

Secondary Outcomes (9)

• Clinical Episodes of Uncomplicated Febrile Illness

  Passive surveillance in all health centers within the study area starting 1 April 2020 until 31 March 2022.

• Hospital Admissions With Malaria, Including Severe Malaria

  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

• Prevalence of Malaria Parasitaemia, Including Gametocytaemia and the Prevalence of Moderate and Severe Anemia and Malnutrition

  Blood sample collection during 2-week cross sectional survey at the end of each malaria transmission season (November 2020/21).).

• Serious Adverse Events (SAEs)

  Through study completion (for 2 years), each SAE will be treated and documented according to ICH-GCP.

• Immune Response to the Vaccine (Anti-CSP Antibody Concentrations)

  Blood sample collection 0-7 days before and one month after the booster doses (year 1 and 2).

Study Arms (3)

SMC with SP+AQ

ACTIVE COMPARATOR

Administration of tetanus/diphtheria toxoids vaccine followed by 4 cycles of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1 and 2.

Biological: Tetanus/diphtheria toxoids; Drug: SMC with SP+AQ

RTS,S/AS01

ACTIVE COMPARATOR

Administration of the malaria vaccine RTS,S/AS01 followed by 4 cycles of SMC with placebo in Year 1 and 2.

Biological: RTS,S/AS01; Drug: SMC placebo

RTS,S/AS01 plus SMC with SP+AQ

ACTIVE COMPARATOR

Administration of the malaria vaccine RTS,S/AS01 followed by 4 cycles of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1 and 2.

Drug: SMC with SP+AQ; Biological: RTS,S/AS01

Interventions

Tetanus/diphtheria toxoids BIOLOGICAL

One dose of tetanus/diphtheria toxoids vaccine (June) in year 1 and year 2.

SMC with SP+AQ

SMC with SP+AQ DRUG

Year 1 and 2 (2020/21) Four cycles of SMC (SP+AQ) (July, August, September, October). One cycle 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.

RTS,S/AS01 plus SMC with SP+AQ; SMC with SP+AQ

RTS,S/AS01 BIOLOGICAL

One booster dose of RTSS/AS01 (June) in year 1 and 2.

RTS,S/AS01; RTS,S/AS01 plus SMC with SP+AQ

SMC placebo DRUG

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

RTS,S/AS01

Eligibility Criteria

• Age: 3 Years - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• The child had been enrolled in the initial phase of the trial of seasonal vaccination with the RTS,S/AS01 vaccine
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• Malaria Research and Training Center, Bamako, Mali: collaborator
• Institut de Recherche en Sciences de la Sante, Burkina Faso: collaborator

Study Sites (2)

Institut de Recherche en Sciences de la Santé

Ouagadougou, Direction Régionale de l'Ouest, Burkina Faso

Location

Malaria Research & Training Center

Bamako, Mali

Location

Related Publications (1)

• Dicko A, Ouedraogo JB, Zongo I, Sagara I, Cairns M, Yerbanga RS, Issiaka D, Zoungrana C, Sidibe Y, Tapily A, Nikiema F, Sompougdou F, Sanogo K, Kaya M, Yalcouye H, Dicko OM, Diarra M, Diarra K, Thera I, Haro A, Sienou AA, Traore S, Mahamar A, Dolo A, Kuepfer I, Snell P, Grant J, Webster J, Milligan P, Lee C, Ockenhouse C, Ofori-Anyinam O, Tinto H, Djimde A, Chandramohan D, Greenwood B. Seasonal vaccination with RTS,S/AS01E vaccine with or without seasonal malaria chemoprevention in children up to the age of 5 years in Burkina Faso and Mali: a double-blind, randomised, controlled, phase 3 trial. Lancet Infect Dis. 2024 Jan;24(1):75-86. doi: 10.1016/S1473-3099(23)00368-7. Epub 2023 Aug 22.

  PMID: 37625434 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Interventions

Tetanus Toxoid; Clinical Trials Data Monitoring Committees; RTS,S-AS01 vaccine

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Toxoids; Vaccines; Biological Products; Complex Mixtures; Professional Staff Committees; Quality Assurance, Health Care; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Professor Daniel Chandramohan
• Organization: London School of Hygiene and Tropical Medicine

daniel.chandramohan@lshtm.ac.uk

+447570410351

Study Officials

• 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)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2020
• First Posted: March 24, 2020
• Study Start: April 1, 2020
• Primary Completion: March 31, 2022
• Study Completion: March 31, 2022
• Last Updated: September 20, 2024
• Results First Posted: September 20, 2024

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

BU (1); MA (1)