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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02543086




Registration number
NCT02543086
Ethics application status
Date submitted
23/07/2015
Date registered
7/09/2015
Date last updated
23/07/2019

Titles & IDs
Public title
Effectiveness of KAE609 in Reducing Asexual & Sexual Blood-stage P.Falciparum Infection & Infectivity to Mosquitos
Scientific title
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
Secondary ID [1] 0 0
CKAE609A2109
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Plasmodium Falciparum Malaria 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - KAE609
Treatment: Drugs - Piperaquine Phosphate

Experimental: Multiple Sequential Cohort - 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).


Treatment: Drugs: KAE609
Study drug

Treatment: Drugs: 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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
36 days
Secondary outcome [1] 0 0
Plasma Pharmacokinetics (PK) of KAE609: Area Under the Plasma Concentration-time Curve (AUC) - It will be measured by Area Under the Concentration-Time Curve (AUC) from the time of dosing to the last quantifiable concentration
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
Safety and Tolerability as measured by adverse events (including serious) for incidence, KAE609 (and inoculum) relatedness and severity - Adverse events (including serious) will be recorded during the study and will be rated according to incidence, relation to study drug (inoculum) and severity
Timepoint [2] 0 0
From day of screening until end of study (day 36)

Eligibility
Key inclusion criteria
1. Written informed consent must be obtained before any assessment is performed.

2. 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.

3. Body weight, minimum 50.0 kg, body mass index (BMI) between 18.0 and 32.0 kg/m2,
inclusive.

4. Certified as healthy by a comprehensive clinical assessment.

5. Normal standard 12-lead electrocardiogram (ECG).

6. Laboratory parameters within the normal range.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Any history of malaria or participation to a previous malaria challenge study

2. 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

3. Has evidence of increased cardiovascular disease risk

4. History of splenectomy

5. Presence or history of drug hypersensitivity, or allergic disease diagnosed

6. Presence of current or suspected serious chronic diseases

7. History of malignancy of any organ system

8. Presence of acute infectious disease or fever (e.g., sub-lingual temperature

- 38.5°C) within the five days prior to inoculation with malaria parasites.

9. Participation in any investigational product study within the 12 weeks preceding the
study.

10. Participant who has ever received a blood transfusion.

11. History or presence of alcohol abuse

12. Any vaccination within the last 28 days.

13. Any corticosteroids, anti-inflammatory drugs, immunomodulators or anticoagulants.

14. Any recent (< 1 month) or current systemic therapy with an antibiotic or drug with
potential antimalarial activity (including chloroquine, piperaquine, tetracycline,
azithromycin, clindamycin, hydroxychloroquine,).

15. Medicinal products that are known to prolong the QTc interval.

16. Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen,
antihepatitis B core antibodies (anti-HBc Ab), anti-hepatitis C virus (anti-HCV)
antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti
HIV2 Ab).

17. Known severe reaction to mosquito bites other than local itching and redness

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Novartis Investigative Site - Brisbane
Recruitment postcode(s) [1] 0 0
4006 - Brisbane

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Medicine for Malaria Venture
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02543086
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
James McCarthy, MD FRACP
Address 0 0
Q-Pharm Pty Limited
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02543086