Controlled Human Malaria Infection Model for Evaluation of Transmission-Blocking Interventions - Study 1
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This is a single-center, open label study. The primary aim of this project is to develop a
      controlled human malaria infection transmission model ("CHMI-trans") or "challenge model" to
      evaluate the capacity of vaccines, biologics (monoclonal antibodies, or mAbs), and drugs to
      block malaria parasite transmission by assessing infectiousness of Plasmodium falciparum (Pf)
      gametocyte carriers for Anopheles mosquitoes.
    

Detailed description: 
      A total of 32 volunteers will be randomly assigned to four groups (n=8) and subjected to a
      standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes
      (3D7 clone). Treatment is subsequently initiated to induce gametocytaemia (treatment 1, DT1)
      and to clear pathogenic asexual parasites whilst leaving gametocytes unaffected (treatment 2,
      DT2). At the end of the study, treatment of all parasite stages is provided following
      national treatment guidelines (end treatment, ET).

      Once malaria infections are detected by 18S qPCR positive (day of treatment 1 [DT1]), groups
      1 and 2 will be treated with a course of subcurative sulfadoxine-pyrimethamine (SP) (SP low,
      500mg/25mg). Groups 3 and 4 will receive piperaquine (Pip) in a low-dose (Pip low, 480 mg).
      After DT1, volunteers will receive a curative treatment (DT2) when a recrudescence of asexual
      parasitaemia occurs or on day 21 post challenge infection, whichever comes first. Volunteers
      in group 1 (SP low/SP high) will be treated with sulfadoxine-pyrimethamine (1000mg/50mg) and
      group 2 (SP low/Pip high) with piperaquine (960mg). Volunteers in group 3 (Pip low/Pip high)
      will be treated with piperaquine (960mg) and group 4 (Pip low/SP high) with
      sulfadoxine-pyrimethamine (1000mg/50mg). To ensure the radical clearance of all parasite
      stages, all volunteers will receive a final treatment (ET) according to national guidelines
      with atovaquone/proguanil (Malarone®) on day 42. Daily blood samples will allow detailed
      quantification of gametocytes, gametocyte sex ratio and ex vivo assessments of gametocyte
      fitness.
    

Intervention name(s): Sulfadoxine-pyrimethamine (low dose); Piperaquine (low dose); Sulfadoxine-pyrimethamine (high dose); Piperaquine (high dose); malaria challenge infection, P. falciparum 3D7; Atovaquone-proguanil
Intervention type(s): Drug; Drug; Drug; Drug; Biological; Drug
Intervention description(s): - subcurative regimen (500mg/25mg); - subcurative regimen (480 mg); - curative regimen (1000mg/50mg); - curative regimen (960 mg); malaria challenge infection by P. falciparum 3D7-infected mosquito bites; - curative regimen: 1000/400 mg, for 3 days
Other intervention name(s): Fansidar; piperaquine phosphate; Fansidar; piperaquine phosphate; 3D7 Plasmodium falciparum; Malarone
Intervention MeSH terms: Pyrimethamine; Piperaquine; Sulfadoxine; Fanasil, pyrimethamine drug combination; Atovaquone; Proguanil; Atovaquone, proguanil drug combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other