A Study to Find the Minimum Inhibitory Concentration of KAE609 in Adult Male Patients With P. Falciparum Monoinfection

An Open-label Study to Find the Minimum Inhibitory Concentration(MIC) of KAE609 in Adult Male Patients With Acute, Uncomplicated Malaria Due to Plasmodium Falciparum Monoinfection

This study aims to determine the Minimum Inhibitory Concentration of KAE609 in adult male patients with acute, uncomplicated malaria due to P.falciparum monoinfection after single dosing with KAE609

Study Overview

• Status: Completed
• Conditions: Malaria
• Intervention / Treatment: Drug: KAE609

Detailed Description

There will be a total of approximately 45 patients recruited into this study and six doses of KAE609 and will be investigated.The dose groups will run in sequence. Patient will be given a single dose of KAE609 and be followed up for 42 days.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• Vietnam
  • Ho Chi Minh, Vietnam
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Monoinfection with P. falciparum confirmed by microscopy
• Asexual P. falciparum parasitemia count of 5,000 to 50,000/µL
• Axillary temperature ≥37.5 ºC or oral/tympanic/rectal temperature ≥38 ºC; or similar documented temperature during the previous 24 hours
• Body weight between 40 to 90 kg

Key Exclusion Criteria:

• Signs and symptoms of severe malaria according to World Health Organization (WHO) 2010 criteria
• Mixed Plasmodium infection, i.e. infection with more than one species of malaria parasites
• Use of other investigational drugs within 30 days or within 5 half-lives of enrollment, whichever is longer
• History of antimalarial use within 2 months of screening
• Use of any antibiotics with antimalarial activity or other prohibited medication within 14 days of screening
• Long QT syndrome or QTc using Fridericia's formula >430 msec
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
• Hemoglobin level <10 g/dL
• Liver disease or injury as indicated by elevated liver tests such as SGPT (ALT) or SGOT (AST) >2 times the upper limit of normal
• Renal dysfunction as indicated by serum creatinine >2 times the upper limit of normal in the absence of dehydration; in case of dehydration, serum creatinine should be <2 times the upper limit of normal after oral or parental rehydration
• Known to be immunocompromised (including HIV infection) or are receiving immunosuppressive therapy at the time or enrollment; HIV testing is not required
• Known history of hepatitis B or C; testing is not required
• Febrile condition due to diseases other than malaria (e.g. acute lower respiratory tract infection), known underlying chronic or severe disease (e.g. cardiac, hepatic, renal, gastrointestinal, neurologic, or psychiatric disease), or any condition precluding enrollment into this study according to the investigator
• Severe vomiting defined as >3 times during the previous 24 hours or inability to tolerate oral medication; severe diarrhea defined as ≥3 watery stools during the previous 24 hours
• Severe malnutrition defined by a body mass index (BMI) <18.5 kg/m2 or unintentional loss of weight ≥10% with evidence of suboptimal intake resulting in loss of subcutaneous fat and/or severe muscle wasting
• Active tuberculosis or history of taking anti-tuberculosis medications within 24 months prior to screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose 1: 30 mg; Single dose of KAE609 30 mg	Drug: KAE609; Patients will receive KAE609 single dose at a different dose level in each cohort.
Experimental: Dose 2: 20 mg; Single dose of KAE609 20 mg	Drug: KAE609; Patients will receive KAE609 single dose at a different dose level in each cohort.
Experimental: Dose 3: 10 mg; Single dose of KAE609 10 mg	Drug: KAE609; Patients will receive KAE609 single dose at a different dose level in each cohort.
Experimental: Dose 4: 15 mg; Single dose of KAE609 15 mg	Drug: KAE609; Patients will receive KAE609 single dose at a different dose level in each cohort.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimum Inhibitory Concentration (MIC) of KAE609	To observe the exposure-response (PK/PD) relationship for a single dose of KAE609. The key parameter is MIC, defined as the concentration at which the relative rate of change in parasitemia is equal to zero. Approximation of MIC will assist in identifying the optimal dose of KAE609, which will be one component of a future combination antimalarial. MIC could not be determined due to small sample size no data was collected from any participants.	Up to Day 8 after a single dose of KAE609

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Time to Parasite Clearance	Parasite clearance time will be estimated using thick/thin blood films.	pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 54, 60, 66, 72 hours post dose of KAE609
Median Time to Fever Clearance	Fever is monitored on participants every 4 hours for the first 24 hours, then every 6 hours until negative reading obtained.	Day 1 to Day 5
Percentage of Patients PCR-corrected Cure Rate by Day 28, Day 35 & Day 42	PCR-corrected cure rate after a single dose of KAE609 by Day 28, Day 35 & Day 42. PCR-corrected cure rate accounts for failures due to reappearance of parasites that were present in the blood before treatment (i.e. recrudescent infection) but not for failures due to a post-treatment inoculation (i.e. new infection).	Day 28, Day 35 & Day 42

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Hien TT, White NJ, Thuy-Nhien NT, Hoa NT, Thuan PD, Tarning J, Nosten F, Magnusson B, Jain JP, Hamed K. Estimation of the In Vivo MIC of Cipargamin in Uncomplicated Plasmodium falciparum Malaria. Antimicrob Agents Chemother. 2017 Jan 24;61(2):e01940-16. doi: 10.1128/AAC.01940-16. Print 2017 Feb.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: April 17, 2013
• First Submitted That Met QC Criteria: April 17, 2013
• First Posted (Estimate): April 19, 2013

Study Record Updates

• Last Update Posted (Estimate): October 31, 2016
• Last Update Submitted That Met QC Criteria: September 14, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Malaria, KAE609
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria
• Other Study ID Numbers: CKAE609A2201