NCT02543086

Effectiveness of KAE609 in Reducing Asexual & Sexual Blood-stage P.Falciparum Infection & Infectivity to Mosquitos

A Phase1 Interventional Sequential Single Site Study to Characterize the Effectiveness of Oral KAE609 in Reducing Asexual & Sexual Blood-stage P. Falciparum Following Inoculation in Healthy-volunteers & Subsequent Infectivity to Mosquitoes

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

This is a single-center open label study conducted in multiple sequential cohorts using Induced Blood Stage Malaria infection in healthy volunteers to characterize the effectiveness of KAE609 against sexual and asexual blood stage forms of Plasmodium falciparum. This study is divided in 2 parts (Part A and part B). A total of 8 healthy volunteers per cohort will be enrolled. Based on the results of Part A, Part B will be undertaken to evaluate the effect of KAE609 following pretreatment with Piperaquine on sexual stage/gametocytemia and its activity as an inhibitor of onward transmission to mosquito vectors using experimental mosquito feeding assays.

Detailed description

This is single center multiple sequential Cohort study divided in 2 parts (Part A and part B). A total of 8 healthy volunteers per cohort will be enrolled in Part A, which will focus on characterizing the antiparasitic activity of KAE609 after single dose administration in the human Induced Blood Stage Malaria model. Once Part A is completed, Part B will evaluate the effect of KAE609 following pre-treatment with Piperaquine on sexual stage/gametocytemia and its activity as an inhibitor of onward transmission to mosquito vectors using experimental mosquito feeding assays. For Part A the threshold for commencement of treatment for an individual subject will occur if Quantitative-Polymerase Chain Reaction quantification of all participants in that Cohort is ≥ 1,000 parasites/mL or if Quantitative-Polymerase Chain Reaction quantification of any participant is ≥ 5,000 parasites/mL, and there is clinical evidence of malaria, as defined by a Clinical symptom score ≥6. The First cohort will be dosed with a single dose of KAE609. During Part A, an additional second single-dose of KAE609 for subsequent cohorts may be tested (\~15 days after first dose of KAE609 but may vary) if sexual parasitemia is identified. Subsequent cohorts of part A (An) will be dosed based on the results of first cohort (A1). For Part B, the threshold for commencement of treatment for an individual subject will be when Polymerase Chain Reaction quantification of all participants is ≥ 5,000 parasites/mL or if the Polymerase Chain Reaction quantification of any participant is ≥ 5,000 parasites/mL and is accompanied by a clinical symptom score ≥6, before all participants have reached the treatment threshold (PCR quantification of ≥ 5,000), then treatment of that participant will begin within a 24 h period. Cohort B will receive a pre-treatment with Piperaquine (480 mg) followed by KAE609 (\~15 days) after Piperaquine. Following initial treatment with KAE609 (Part A) or Piperaquine (Part B) on Day 1, participants will be followed up as in-subjects for at least 72 hours to ensure tolerance of the treatment and clinical response. If subjects are clinically well as per judgment of the Investigator, they will be discharged and will be monitored on an outpatient basis for safety and clearance of malaria parasites via Quantitative-Polymerase Chain Reaction. If any study subjects in a cohort in Part A show evidence of gametocytemia after initial treatment with KAE609, a second single-dose of KAE609 will be administered to those subjects as out patient. In part B where significant gametocytemia is expected because the initial Piperaquine treatment is not expected to clear gametocytes, a single dose of KAE609 will be administered at the time of peak gametocytemia. The KAE609 dose for Part B will be selected during the study, based on Pharmacokinetic/Pharmacodynamic and safety analysis of Part A. If recrudescent asexual parasitemia is identified, compulsory commencement of rescue medication will be used. Treatment for recrudescence will be a single dose of Piperaquine only for Part A. In addition, compulsory terminal curative treatment will be administered to all participants at the end of study. Participants will be monitored for three days to ensure adherence to the rescue medication therapy. Adverse events will be monitored via telephone monitoring, within the clinical research unit, and on out-subject review after malaria challenge inoculation and antimalarial study drug administration. Blood samples for safety evaluation, malaria monitoring, and red blood cell antibodies will be drawn at screening and/ or baseline and at nominated times after malaria challenge.

Conditions

• Plasmodium Falciparum Malaria

Interventions

Type	Name	Description
DRUG	KAE609	Study drug
DRUG	Piperaquine Phosphate	Pre-administration of Piperaquine Phosphate will be done to eliminate the asexual form of the parasite and induce gametocytaemia before characterizing the activity of KAE609 in clearing sexual blood stage parasites from the blood of healthy subjects in the Induced Blood Stage Malaria Challenge model in Part B of study

Timeline

• Start date: 2015-07-01
• Primary completion: 2015-09-01
• Completion: 2015-09-01
• First posted: 2015-09-07
• Last updated: 2019-07-23

Locations

1 site across 1 country: Australia