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

NCT02543086 | Terminated Phase 1

• 1 other identifier: CKAE609A2109
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Plasmodium Falciparum Malaria

Keywords

Phase 1, malaria, inoculum, P. falciparum, KAE609, Piperaquine

Outcome Measures

Primary Outcomes (1)

• Parasitic count in blood by Polymerase Chain Reaction

  Clearance of Plasmodium falciparum asexual and sexual blood stage parasites from the blood of healthy subjects in the Induced Blood Stage Malaria Challenge model

  36 days

Secondary Outcomes (2)

• Plasma Pharmacokinetics (PK) of KAE609: Area Under the Plasma Concentration-time Curve (AUC)

  Day 1: 0, 1, 2, 3, 4, 8, 12, 16 hours, then 24, 36, 48, 72, 96 and 120 hours post dose Days 2 to 6, Day 15 0, 12 hours post dose then 24, 48, 72, 96 and 120 hours post dose Day 16 to Day 20

• Safety and Tolerability as measured by adverse events (including serious) for incidence, KAE609 (and inoculum) relatedness and severity

  From day of screening until end of study (day 36)

Study Arms (1)

Multiple Sequential Cohort

EXPERIMENTAL

This study is divided in 2 parts (Part A and part B). Each participant in each of the cohorts will be inoculated with viable parasites of Plasmodium falciparum-infected human erythrocytes administered intravenously. For Part A \& Part B, commencement of treatment will be determined by Quantitative-Polymerase Chain Reaction results. The First cohort of Part A (A1) will be dosed with a single dose of KAE609. During Part A, an additional second single-dose of KAE609 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). Subjects enrolled in Cohort B will receive a pre-treatment with Piperaquine followed by KAE609 (\~15 days).

Drug: KAE609; Drug: Piperaquine Phosphate

Interventions

KAE609 DRUG

Study drug

Multiple Sequential Cohort

Piperaquine Phosphate DRUG

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

Multiple Sequential Cohort

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Written informed consent must be obtained before any assessment is performed.
• Male and females participants between 18 and 55 years of age. Female participants between 18 and 55 years of age have to be of non-child bearing potential.
• Body weight, minimum 50.0 kg, body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive.
• Certified as healthy by a comprehensive clinical assessment.
• Normal standard 12-lead electrocardiogram (ECG).
• Laboratory parameters within the normal range.

You may not qualify if:

• Any history of malaria or participation to a previous malaria challenge study
• Spent more than four weeks in a malaria-endemic country during the past 12 months or planned travel to a malaria endemic area during the course of the study
• Has evidence of increased cardiovascular disease risk
• History of splenectomy
• Presence or history of drug hypersensitivity, or allergic disease diagnosed
• Presence of current or suspected serious chronic diseases
• History of malignancy of any organ system
• Presence of acute infectious disease or fever (e.g., sub-lingual temperature
• °C) within the five days prior to inoculation with malaria parasites.
• Participation in any investigational product study within the 12 weeks preceding the study.
• Participant who has ever received a blood transfusion.
• History or presence of alcohol abuse
• Any vaccination within the last 28 days.
• Any corticosteroids, anti-inflammatory drugs, immunomodulators or anticoagulants.
• Any recent (\< 1 month) or current systemic therapy with an antibiotic or drug with potential antimalarial activity (including chloroquine, piperaquine, tetracycline, azithromycin, clindamycin, hydroxychloroquine,).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• Medicine for Malaria Venture: collaborator

Study Sites (1)

Novartis Investigative Site

Brisbane, Queensland, 4006, Australia

Location

Related Publications (1)

• McCarthy JS, Abd-Rahman AN, Collins KA, Marquart L, Griffin P, Kummel A, Fuchs A, Winnips C, Mishra V, Csermak-Renner K, Jain JP, Gandhi P. Defining the Antimalarial Activity of Cipargamin in Healthy Volunteers Experimentally Infected with Blood-Stage Plasmodium falciparum. Antimicrob Agents Chemother. 2021 Jan 20;65(2):e01423-20. doi: 10.1128/AAC.01423-20. Print 2021 Jan 20.

  PMID: 33199389 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Interventions

NITD 609; piperaquine

Condition Hierarchy (Ancestors)

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

Study Officials

• James McCarthy, MD FRACP

  Q-Pharm Pty Limited

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2015
• First Posted: September 7, 2015
• Study Start: July 1, 2015
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: July 23, 2019

Record last verified: 2019-07

Locations

AU (1)