Parasite Clearance and Protection From Infection (PCPI) in Zambia

NCT06166498 | Completed Phase 3 DMC

• 1 other identifier: 2022-KEP-813
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

The Zambia PCPI study will measure the effect of the parasite genotypes associated with SP resistance on parasite clearance and protection from infection when exposed to SP. The total number of participants is expected to be 600 healthy between 3 to 5 years old who have no symptoms of malaria infection of which 400 children will be assigned to the SP group and 200 to the AS group. The results of this study will allow to measure the effect of the parasite genotypes associated with SP resistance on parasite clearance and protection from infection when exposed to SP.

Conditions

Malaria

Keywords

Malaria; Perennial malaria chemoprevention (PMC); Sulfadoxine-pyrimethamine (SP); Chemoprevention; Drug resistance

Outcome Measures

Primary Outcomes (2)

• Parasite clearance

  Time to clearance of parasite genotypes among SP recipients who were positive on Day 0 by qPCR presence/absence of Pfdhps K540E and measured to Day 63

  28 days (total follow up 63 days post SP dose)

• Protection from infection

  (a) Mean duration of SP protection against parasite genotypes determined by Pfdhps gene sequence presence/absence of Pfdhps K540E among SP recipients who were parasite-free on Day 0 by qPCR (b) Mean duration of symptom-free status among SP recipients who were parasite free on Day 0 by qPCR, stratified by parasite Pfdhps genotype at time of febrile malaria episode

  28 days (total follow up 63 days post SP dose)

Secondary Outcomes (2)

• Parasite clearance

  7 days (day -7 until day 0)

• Protection from infection

  Time Frame: 35 days (day 0 until day 35)

Study Arms (2)

Sulphadoxine-pyrimethamine (SP)

ACTIVE COMPARATOR

Children in the SP group will receive a 7-day course of placebo artesunate (at day -7, -6, -5, -4, -3, -2, and -1), followed by the standard of care, 5 doses of SP.

Drug: SP (Macleods Pharmaceuticals Ltd)

Artesunate monotherapy (AS)

ACTIVE COMPARATOR

Children in the AS group will receive a 7-day course of 7-day course of active artesunate (at day -7, -6, -5, -4, -3, -2, and -1), followed by placebo SP.

Drug: AS (Guilin Pharmaceuticals)

Interventions

SP (Macleods Pharmaceuticals Ltd) DRUG

Children who weigh \<10kg will receive Sulfadoxine-pyrimethamine paediatric formulation (250mg/12.5mg) dispersable tablets; children who weigh \>10kg will receive 500mg sulfadoxine plus 25mg pyrimethamine

Also known as: Sulfadoxine-pyrimethamine

Sulphadoxine-pyrimethamine (SP)

AS (Guilin Pharmaceuticals) DRUG

Children will receive 4 mg/kg/day for 7 days

Also known as: Artesunate

Artesunate monotherapy (AS)

Eligibility Criteria

• Age: 3 Years - 5 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Be 3-5 years old
• Exhibit no symptoms of malaria
• Have parents/guardians willing to have their child participate in all follow-up visits and seek care from study staff
• Reside in the study catchment area

You may not qualify if:

• Have evidence of acute illness as determined by clinical examination
• Exhibit symptoms of malaria (axillary fever ≥ 37.5 °C and / or history of fever in past 48 hours)
• Have known allergy to study medications
• Have received antimalarial treatment or azithromycin within 28 days prior to screening
• Be concomitantly receiving co-trimoxazole (trimethoprim-sulfamethoxazole)
• Be categorised as severely malnourished according to WHO child growth standards

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead

Study Sites (1)

Nchelenge District

Nchelenge, Luapula Province, Zambia

Location

Related Publications (16)

• World Health Organization. WHO guidelines for malaria, 3 June 2022: World Health Organization, 2022.

  BACKGROUND

• Aponte JJ, Schellenberg D, Egan A, Breckenridge A, Carneiro I, Critchley J, Danquah I, Dodoo A, Kobbe R, Lell B, May J, Premji Z, Sanz S, Sevene E, Soulaymani-Becheikh R, Winstanley P, Adjei S, Anemana S, Chandramohan D, Issifou S, Mockenhaupt F, Owusu-Agyei S, Greenwood B, Grobusch MP, Kremsner PG, Macete E, Mshinda H, Newman RD, Slutsker L, Tanner M, Alonso P, Menendez C. Efficacy and safety of intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in African infants: a pooled analysis of six randomised, placebo-controlled trials. Lancet. 2009 Oct 31;374(9700):1533-42. doi: 10.1016/S0140-6736(09)61258-7. Epub 2009 Sep 16.

  PMID: 19765816 BACKGROUND

• Schellenberg D, Menendez C, Kahigwa E, Aponte J, Vidal J, Tanner M, Mshinda H, Alonso P. Intermittent treatment for malaria and anaemia control at time of routine vaccinations in Tanzanian infants: a randomised, placebo-controlled trial. Lancet. 2001 May 12;357(9267):1471-7. doi: 10.1016/S0140-6736(00)04643-2.

  PMID: 11377597 BACKGROUND

• Chandramohan D, Owusu-Agyei S, Carneiro I, Awine T, Amponsa-Achiano K, Mensah N, Jaffar S, Baiden R, Hodgson A, Binka F, Greenwood B. Cluster randomised trial of intermittent preventive treatment for malaria in infants in area of high, seasonal transmission in Ghana. BMJ. 2005 Oct 1;331(7519):727-33. doi: 10.1136/bmj.331.7519.727.

  PMID: 16195288 BACKGROUND

• Macete E, Aide P, Aponte JJ, Sanz S, Mandomando I, Espasa M, Sigauque B, Dobano C, Mabunda S, DgeDge M, Alonso P, Menendez C. Intermittent preventive treatment for malaria control administered at the time of routine vaccinations in Mozambican infants: a randomized, placebo-controlled trial. J Infect Dis. 2006 Aug 1;194(3):276-85. doi: 10.1086/505431. Epub 2006 Jun 30.

  PMID: 16826474 BACKGROUND

• Kobbe R, Kreuzberg C, Adjei S, Thompson B, Langefeld I, Thompson PA, Abruquah HH, Kreuels B, Ayim M, Busch W, Marks F, Amoah K, Opoku E, Meyer CG, Adjei O, May J. A randomized controlled trial of extended intermittent preventive antimalarial treatment in infants. Clin Infect Dis. 2007 Jul 1;45(1):16-25. doi: 10.1086/518575. Epub 2007 May 29.

  PMID: 17554695 BACKGROUND

• Mockenhaupt FP, Reither K, Zanger P, Roepcke F, Danquah I, Saad E, Ziniel P, Dzisi SY, Frempong M, Agana-Nsiire P, Amoo-Sakyi F, Otchwemah R, Cramer JP, Anemana SD, Dietz E, Bienzle U. Intermittent preventive treatment in infants as a means of malaria control: a randomized, double-blind, placebo-controlled trial in northern Ghana. Antimicrob Agents Chemother. 2007 Sep;51(9):3273-81. doi: 10.1128/AAC.00513-07. Epub 2007 Jul 16.

  PMID: 17638703 BACKGROUND

• Grobusch MP, Lell B, Schwarz NG, Gabor J, Dornemann J, Potschke M, Oyakhirome S, Kiessling GC, Necek M, Langin MU, Klein Klouwenberg P, Klopfer A, Naumann B, Altun H, Agnandji ST, Goesch J, Decker M, Salazar CL, Supan C, Kombila DU, Borchert L, Koster KB, Pongratz P, Adegnika AA, Glasenapp Iv, Issifou S, Kremsner PG. Intermittent preventive treatment against malaria in infants in Gabon--a randomized, double-blind, placebo-controlled trial. J Infect Dis. 2007 Dec 1;196(11):1595-602. doi: 10.1086/522160. Epub 2007 Oct 25.

  PMID: 18008242 BACKGROUND

• Mayor A, Serra-Casas E, Sanz S, Aponte JJ, Macete E, Mandomando I, Puyol L, Berzosa P, Dobano C, Aide P, Sacarlal J, Benito A, Alonso P, Menendez C. Molecular markers of resistance to sulfadoxine-pyrimethamine during intermittent preventive treatment for malaria in Mozambican infants. J Infect Dis. 2008 Jun 15;197(12):1737-42. doi: 10.1086/588144.

  PMID: 18419347 BACKGROUND

• Gupta H, Macete E, Bulo H, Salvador C, Warsame M, Carvalho E, Menard D, Ringwald P, Bassat Q, Enosse S, Mayor A. Drug-Resistant Polymorphisms and Copy Numbers in Plasmodium falciparum, Mozambique, 2015. Emerg Infect Dis. 2018 Jan;24(1):40-48. doi: 10.3201/eid2401.170864.

  PMID: 29260689 BACKGROUND

• Gosling RD, Gesase S, Mosha JF, Carneiro I, Hashim R, Lemnge M, Mosha FW, Greenwood B, Chandramohan D. Protective efficacy and safety of three antimalarial regimens for intermittent preventive treatment for malaria in infants: a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Oct 31;374(9700):1521-32. doi: 10.1016/S0140-6736(09)60997-1. Epub 2009 Sep 16.

  PMID: 19765815 BACKGROUND

• Naidoo I, Roper C. Mapping 'partially resistant', 'fully resistant', and 'super resistant' malaria. Trends Parasitol. 2013 Oct;29(10):505-15. doi: 10.1016/j.pt.2013.08.002. Epub 2013 Sep 9.

  PMID: 24028889 BACKGROUND

• Oguike MC, Falade CO, Shu E, Enato IG, Watila I, Baba ES, Bruce J, Webster J, Hamade P, Meek S, Chandramohan D, Sutherland CJ, Warhurst D, Roper C. Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V. Int J Parasitol Drugs Drug Resist. 2016 Dec;6(3):220-229. doi: 10.1016/j.ijpddr.2016.08.004. Epub 2016 Sep 29.

  PMID: 27821281 BACKGROUND

• ACCESS-SMC Partnership. Effectiveness of seasonal malaria chemoprevention at scale in west and central Africa: an observational study. Lancet. 2020 Dec 5;396(10265):1829-1840. doi: 10.1016/S0140-6736(20)32227-3.

  PMID: 33278936 BACKGROUND

• World Health Organisation. Malaria chemoprevention efficacy study protocol. Geneva: World Health Organisation, 2022.

  BACKGROUND

• Martinez-Vega R, Chaponda M, Mousa A, Gwasupika J, Chaponda EB, Daka V, Mwanza S, Chipunga M, Beshir KB, Chopo-Pizarro A, Kaur H, Okell L, Hansson H, Hocke EF, Alifrangis M, Gosling R, Roper C, Sutherland C, Chico RM. Parasite clearance and protection from Plasmodium falciparum infection (PCPI): a two-arm, parallel, double-blinded, placebo-controlled, randomised trial of presumptive sulfadoxine-pyrimethamine versus artesunate monotherapy among asymptomatic children 3-5 years of age in Zambia. BMC Infect Dis. 2025 Nov 11;25(1):1547. doi: 10.1186/s12879-025-11975-3.

  PMID: 41219832 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

fanasil, pyrimethamine drug combination; Artesunate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons

Study Officials

• R Matthew Chico, MPH, PhD

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Fully placebo controlled
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Children assigned to group 1-SP will receive a 7-day course of placebo artesunate, whereas children in the group 2-AS will be given a 7-day course of active artesunate. This will span Day -7, -6, -5, -4, -3, -2, and -1. Then, on Day 0, children who had been given placebo artesunate will receive SP, whereas children in the AS group will receive placebo SP.

Study Record Dates

• First Submitted: November 29, 2023
• First Posted: December 12, 2023
• Study Start: July 24, 2024
• Primary Completion: December 19, 2024
• Study Completion: March 5, 2025
• Last Updated: March 12, 2025

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)