Pharmacy and Poisons Board
Protocol No: ECCT/23/03/07 Date of Protocol: 15-12-2022
Study Title:

(PLATINUM): A multi-part, multi-center PLATform study to assess the efficacy, safety, tolerability and pharmacokinetics of anti-malarial agents administered as monotherapy and/or combination therapy IN patients with Uncomplicated Plasmodium falciparum Malaria
Study Objectives:

Primary objective(s)

Part A:

• To assess the parasite clearance time (PCT) of oral doses of an anti-malarial agent

administered as monotherapy in patients with uncomplicated P. falciparum malaria

 

Part B:

• To assess the 28-day cure rate of an anti-malarial agent administered orally as

combination therapy versus the standard of care (SoC) in patients with uncomplicated

P. falciparum malaria

 

Secondary objective(s)

  • Part A:
    • To assess the 28-day cure rate of an anti-malarial agent administered orally as monotherapy in patients with uncomplicated P. falciparum malaria
  • Part B:
    • To assess the parasite clearance time (PCT) of oral combinations of anti-malarial agents versus the standard of care (SoC) in patients with uncomplicated P. falciparum malaria
    • To assess the 28-day cure rate of an anti-malarial agent administered orally as combination therapy versus the SoC in patients with uncomplicated P. falciparum malaria

 

  • For all parts:
    • To characterize PK of each anti-malarial agent administered orally as monotherapy

[Part A] and/or as combination therapy

[Part B] in patients with uncomplicated P. falciparum malaria

  • To assess the safety and tolerability of each anti-malarial agent administered orally as monotherapy [Part A] and/or as combination therapy versus SoC [Part B] in patients with  uncomplicated P. falciparum malaria

 

 

 

 

Exploratory objective(s)

  • For Part B:
    • To assess the 42-day cure rate of an anti-malarial agent administered as combination therapy versus the SoC in patients with uncomplicated P. falciparum malaria
  • For all parts:
  • To assess the effect of each anti-malarial agent administered orally as monotherapy and/or as combination therapy on parasite clearance dynamics
  • To assess the effect of each anti-malarial agent on drug resistance development
  • To assess the effect of each anti-malarial agent administered orally as monotherapy and as combination therapy on fever clearance time
  • To explore the exposure-response and/ or exposure-protein levels (e.g., alpha-1 glycoprotein) relationship of anti-malarial agent administered as monotherapy and/or as combination therapy
  • To explore the effect of each anti-malarial agent on gametocytes and transmission-blocking potential
  • To explore potential association of biomarker and differential clinical response to each anti-malarial agent
  • Optional DNA collection: To perform genetic research to investigate drug related response mechanisms, to better understand the disease and/or safety and efficacy of each anti-malarial agent

 
Laymans Summary:

Platform study to evaluate the efficacy and safety of anti-malarial agents in patients with uncomplicated Plasmodium falciparum malaria (PLATINUM
Abstract of Study:

Purpose and rationale:

The purpose of this platform study is to evaluate the parasiticidal effect and potential for cure with different anti-malarial agents administered as monotherapy and/or in combination therapy with other anti-malarial agents in adult and adolescent patients with uncomplicated Plasmodium

falciparum malaria. Additionally, the safety, tolerability, and pharmacokinetics of these anti-malarial agents will be evaluated for dose selection for future studies..

 

Primary Objective(s):

Part A: To assess the parasite clearance time (PCT) of oral doses of an antimalarial

agent administered as monotherapy in patients with uncomplicated P. falciparum malaria

Part B: To assess the effect on adjusted 28-day cure rate of an anti-malarial agent administered orally as combination therapy versus the standard of care (SoC) in patients with uncomplicated P. falciparum malaria.

 

Secondary Objective(s)

Part A: To assess the effect on adjusted 28-day cure rate of an anti-malarial agent administered orally as monotherapy in patients with uncomplicated P. falciparum malaria

 

Part B: To assess the parasite clearance time (PCT) of oral combinations of anti-malarial agents versus SoC in patients with uncomplicated P. falciparum malaria

 

All parts:

To characterize PK of each anti-malarial agent administered orally as monotherapy [Part A] and/or as combination therapy [Part B] in patients with uncomplicated P. falciparum malaria

To assess the safety and tolerability of each anti-malarial agent administered orally as monotherapy [Part A] and/or as combination therapy versus SoC [Part B] in patients with uncomplicated P. falciparum malaria

 

Study design

This is a multi-part, multi-center, open-label platform study, including a parallel and adaptive sequential dose level design in Part A followed by an open-label, randomized, controlled design 

in Part B in patients with uncomplicated P. falciparum malaria. Part A will evaluate anti-malarial agents as monotherapy. Part B will evaluate anti-malarial agents as combination therapy.

 

Study Population

 

The study population will consist of male and female patients aged ≥18 years

for Part A and aged ≥12 years for Part B