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

NCT03143218 | Completed Phase 3 Results DMC

• 1 other identifier: ITDCZJ29 - Greenwood
• Study Type: interventional
• Target: 5,920
• Locations: 2 countries
• Sites: 2

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.

Conditions

Malaria,Falciparum; Children, 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 starting from the date of the first dose of study vaccines (April/May 2017) until 31st March 2020- a total of 36 months.

Secondary Outcomes (9)

• Clinical Episodes of Uncomplicated Febrile Illness

  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.

• Hospital Admissions With Malaria, Including Severe Malaria

  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.

• Prevalence of Malaria Infection Not Severe Enough to Warrant a Clinic Visit

  Weekly home visits through study completion from July 2017 - April 2020 to screen study children for malaria.

• 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.

• Serious Adverse Events (SAEs)

  Through study completion (for 30 months), each SAE will be treated and documented according to ICH-GCP.

Other Outcomes (2)

• Acceptability of RTS,S and SMC

  Data collection in Year 3

• Feasibility of Introducing Two Malaria Control Strategies Simultaneously

  Data collection in Year 3

Study Arms (3)

SMC with SP+AQ

ACTIVE COMPARATOR

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®; 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 1,2 and 3.

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 1,2 and 3.

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

Interventions

RABIPUR® BIOLOGICAL

Year 1 (2017) Three doses of rabies vaccine (April, May, June) Year 2 and 3 (2018/19) One dose of Hepatitis A vaccine (June)

SMC with SP+AQ

RTS,S/AS01 BIOLOGICAL

Year 1 (2017) Three doses of RTSS/AS01 (April, May, June) Year 2 and 3 (2018/19) One booster dose of RTSS/AS01 (June)

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

SMC with SP+AQ DRUG

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.

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

SMC placebo DRUG

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

RTS,S/AS01

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

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, Direction Régionale de l'Ouest

Ouagadougou, Burkina Faso

Location

Malaria Research & Training Center

Bamako, Mali

Location

Related Publications (24)

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• Sagara I, Zongo I, Cairns M, Yerbanga RS, Mahamar A, Nikiema F, Tapily A, Sompougdou F, Diarra M, Zoungrana C, Issiaka D, Haro A, Sanogo K, Aziz Sienou A, Kaya M, Traore S, Thera I, Diarra K, Dolo A, Kuepfer I, Snell P, Milligan P, Ockenhouse C, Ofori-Anyinam O, Tinto H, Djimde A, Ouedraogo JB, Dicko A, Chandramohan D, Greenwood B. The Anti-Circumsporozoite Antibody Response of Children to Seasonal Vaccination With the RTS,S/AS01E Malaria Vaccine. Clin Infect Dis. 2022 Sep 10;75(4):613-622. doi: 10.1093/cid/ciab1017.

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• Chandramohan D, Dicko A, Zongo I, Sagara I, Cairns M, Kuepfer I, Diarra M, Tapily A, Issiaka D, Sanogo K, Mahamar A, Sompougdou F, Yerbanga S, Thera I, Milligan P, Tinto H, Ofori-Anyinam O, Ouedraogo JB, Greenwood B. Seasonal malaria vaccination: protocol of a phase 3 trial of seasonal vaccination with the RTS,S/AS01E vaccine, seasonal malaria chemoprevention and the combination of vaccination and chemoprevention. BMJ Open. 2020 Sep 15;10(9):e035433. doi: 10.1136/bmjopen-2019-035433.

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MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Interventions

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

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Professional Staff Committees; Quality Assurance, Health Care; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Professor Brian Greenwood
• Organization: London School of Hygiene and Tropical Medicine

brian.greenwood@lshtm.ac.uk

+442072994707

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: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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

Study Record Dates

• First Submitted: March 22, 2017
• First Posted: May 8, 2017
• Study Start: April 17, 2017
• Primary Completion: March 31, 2020
• Study Completion: March 31, 2020
• Last Updated: April 7, 2022
• Results First Posted: January 28, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

MA (1); BU (1)