ProjektA single center, randomized, double-blind, placebo-controlled, Phase Ib study to evaluate the chemoprotective…
Grunddaten
Titel:
A single center, randomized, double-blind, placebo-controlled, Phase Ib study to evaluate the chemoprotective antimalarial activity of a single dose of MMV390048 against controlled human malaria infection with Plasmodium falciparum sporozoite challenge in non-immune healthy adult volunteers
Laufzeit:
01.01.2018 bis 31.12.2018
Abstract / Kurz- beschreibung:
This study follows the First In Human dose-escalation study of MMV390048 (5 to 120 mg of MMV390048 as a powder-in-bottle formulation), a formulation bioavailability study to establish a suitable tablet formation, and a two-part dose-escalation (40 to 120 mg of MMV390048) / induced blood stage malaria (IBSM) challenge study with the new tablet formulation. After identification of the predicted efficacious MMV390048 plasma concentrations in the IBSM model, the current study will evaluate the efficacy of MMV390048 as a causal chemoprotective agent in a standardized and validated controlled human malaria infection (CHMI) model using direct venous inoculation (DVI) of aseptic, purified, cryopreserved, vialed P. falciparum sporozoites (PfSPZ Challenge).
Three sequential cohorts of healthy men and women of non-childbearing potential (WONCBP) are planned in order to investigate three conditions of administration of MMV390048 to provide proof-of-concept and identify prophylactic regimens for a Phase II program. In the first two cohorts, administration of the investigational medicinal product (IMP) will occur 1 and 7 days before DVI of PfSPZ Challenge. The timing of IMP administration and dose to be administered to the last cohort will be determined based on emerging data from the preceding cohorts, but will not exceed 28 days prior to the challenge nor 120 mg MMV390048.
Primary Objective:
• To assess the chemoprotective activity of a 120 mg or lower single-dose administration of MMV390048, as an early causative and suppressive intervention on P. falciparum infection in non-immune healthy volunteers after DVI of PfSPZ Challenge.
Secondary Objectives:
• To assess the safety and tolerability of MMV390048 for causal and suppressive chemoprotection in non-immune healthy volunteers during CHMI with PfSPZ Challenge
• To assess the safety and tolerability of PfSPZ Challenge to non-immune healthy volunteers after MMV390048 administration
• To assess the single dose pharmacokinetic profile of MMV390048 to 28 days post-dose when administered prior to DVI with PfSPZ Challenge in non-immune healthy volunteers
• To characterize the relationship between MMV390048 exposure and time to P. falciparum parasitaemia (as determined by TBS and qPCR) in non-immune healthy volunteers after DVI of PfSPZ Challenge
• To characterize the potential appearance of parasite following MMV390048 administration.
Exploratory Objectives:
• To estimate the effect of MMV390048 on liver-to-blood inoculum and multiplication rate during early asexual blood stage by qPCR and statistical modelling
• To measure the innate and early adaptive immune response against sporozoite, liver stage and asexual blood stage
To explore the transcriptional profile of the parasite and immune cell populations
Three sequential cohorts of healthy men and women of non-childbearing potential (WONCBP) are planned in order to investigate three conditions of administration of MMV390048 to provide proof-of-concept and identify prophylactic regimens for a Phase II program. In the first two cohorts, administration of the investigational medicinal product (IMP) will occur 1 and 7 days before DVI of PfSPZ Challenge. The timing of IMP administration and dose to be administered to the last cohort will be determined based on emerging data from the preceding cohorts, but will not exceed 28 days prior to the challenge nor 120 mg MMV390048.
Primary Objective:
• To assess the chemoprotective activity of a 120 mg or lower single-dose administration of MMV390048, as an early causative and suppressive intervention on P. falciparum infection in non-immune healthy volunteers after DVI of PfSPZ Challenge.
Secondary Objectives:
• To assess the safety and tolerability of MMV390048 for causal and suppressive chemoprotection in non-immune healthy volunteers during CHMI with PfSPZ Challenge
• To assess the safety and tolerability of PfSPZ Challenge to non-immune healthy volunteers after MMV390048 administration
• To assess the single dose pharmacokinetic profile of MMV390048 to 28 days post-dose when administered prior to DVI with PfSPZ Challenge in non-immune healthy volunteers
• To characterize the relationship between MMV390048 exposure and time to P. falciparum parasitaemia (as determined by TBS and qPCR) in non-immune healthy volunteers after DVI of PfSPZ Challenge
• To characterize the potential appearance of parasite following MMV390048 administration.
Exploratory Objectives:
• To estimate the effect of MMV390048 on liver-to-blood inoculum and multiplication rate during early asexual blood stage by qPCR and statistical modelling
• To measure the innate and early adaptive immune response against sporozoite, liver stage and asexual blood stage
To explore the transcriptional profile of the parasite and immune cell populations
Beteiligte Mitarbeiter/innen
Leiter/innen
Medizinische Fakultät
Universität Tübingen
Universität Tübingen
Lokale Einrichtungen
Abteilung VII, Tropenmedizin
Medizinische Universitätsklinik und Poliklinik (Department)
Kliniken und klinische Institute, Medizinische Fakultät
Kliniken und klinische Institute, Medizinische Fakultät
Geldgeber
Genf, Schweiz