Safety of KAE609 in Adults With Uncomplicated Plasmodium Falciparum Malaria.

Malaria Clinical Trial

Official title:

A Phase 2, Multi-center, Randomized, Open-label, Dose-escalation Study to Determine Safety of Single (QD) and Multiple (3 QD) Doses of KAE609, Given to Adults With Uncomplicated Plasmodium Falciparum Malaria.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03334747
• Other study ID #: CKAE609A2202
• Secondary ID: 207813/Z/17/Z
• Status: Completed
• Phase: Phase 2
• Start date: November 16, 2017
• Est. completion date: November 23, 2019

Study information

• Verified date: October 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

KAE609 will be evaluated primarily for hepatic safety of single and multiple doses in sequential cohorts with increasing doses.This study aims to determine the maximum safe dose of the investigational drug KAE609 in malaria patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 188
• Est. completion date: November 23, 2019
• Est. primary completion date: November 23, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

KEY Inclusion Criteria:

1. Male and female patients = 18 years with a body weight = 45 kg.

2. Microscopic confirmation of acute uncomplicated P. falciparum using by Giemsa-stained thick film.

3. P. falciparum parasitaemia of 500 to 50 000 parasites/µL.

4. Axillary temperature = 37.5ºC or oral/tympanic/rectal temperature = 38.0ºC; or history of fever during the previous 24 hours.

5. Written informed consent must be obtained before any study assessment is performed. If the patient is unable to write, then a witnessed consent according to local ethical standards is permitted.

KEY Exclusion Criteria:

1. Mixed Plasmodium infections.

2. Signs and symptoms of severe malaria according to World Health Organization (WHO) 2016 criteria (WHO 2016).

3. Known liver abnormalities, liver cirrhosis (compensated or decompensated), known active or history of hepatitis B or C (testing not required), known gallbladder or bile duct disease, acute or chronic pancreatitis.

4. Clinical or laboratory evidence of any of the following:

5. AST/ALT > 1.5 x the upper limit of normal range (ULN), regardless of the level of total bilirubin

6. AST/ALT > 1.0 and = 1.5 x ULN and total bilirubin is > ULN

7. Total bilirubin > 2 x ULN, regardless of the level of AST/ALT

8. History of photodermatitis/increased sensitivity to sun.

9. Pregnant or nursing (lactating) women.

10. Known disturbances of electrolyte balance, e.g. hypokalemia, hypocalcemia or hypomagnesemia.

11. Moderate to severe anemia (Hemoglobin level <8 g/dL).

Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum

Intervention

Drug:
• KAE609
Exploration of different doses of KAE609 to establish safety profile.
• Coartem
Control Arm

Locations

Country	Name	City	State
Gabon	Novartis Investigative Site	Lambarene
Ghana	Novartis Investigative Site	Kintampo
Ghana	Novartis Investigative Site	Navrango
Mali	Novartis Investigative Site	Bamako
Mali	Novartis Investigative Site	Sotuba
Rwanda	Novartis Investigative Site	Kigali
Uganda	Novartis Investigative Site	Bushenyi
Uganda	Novartis Investigative Site	Kampala
Uganda	Novartis Investigative Site	Tororo

Sponsors (2)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals	Supported by Wellcome Trust via Grant # Grant Number 207813/Z/17/Z

Countries where clinical trial is conducted

Gabon,  Ghana,  Mali,  Rwanda,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With at Least 2 CTCAE Grades Increase From Baseline in Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST)	The occurrence of at least 2 CTCAE grades increase from baseline in ALT or AST during the 4 weeks study period was evaluated to characterize hepatic safety aspects of single and multiple ascending doses of KAE609 in adult malaria subjects for treatment of uncomplicated malaria caused by plasmodium falciparum. If 2 patients in a 10 patient cohort (Cohorts 1 and 2) or 3 patients in a 20 patient cohort (Cohorts 3, 4 and 5) had at least 2 CTCAE grades increase from Baseline in ALT or AST, recruitment was suspended and a review of liver safety (and any other relevant data) by safety review committee was initiated. Any further progression of the study was based on the decision by the safety review committee.	Day 29
Secondary	Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected and Uncorrected Adequate Clinical and Parasitological Response (ACPR) at Day 15 and Day 29	PCR-corrected and PCR-uncorrected were evaluated at Days 15 and 29 (i.e., 14 and 28 days post-dose). The presence of parasitaemia after 7 days due to reinfection was considered as PCR-corrected ACPR. Missing blood smear data at Day 15 visit and thereafter were not considered as responder for the visit unless there was a later blood smear test indicating no parasitaemia.	Day 15, Day 29
Secondary	Parasite Clearance Time (PCT)	Parasite Clearance Time (PCT) is defined as the time from the first dose until the first total and continued disappearance of asexual parasite forms which remained at least a further 48 hours. In case a patient received rescue medication before (parasite) clearance, the time to event was censored at the first use of rescue medication.	Day 29
Secondary	Fever Clearance Time (FCT)	Fever Clearance Time (FCT) is defined as the time from the first dose until the first time the axillary body temperature decreased below and remained below 37.5°C axillary or 38.0°C oral/tympanic/rectal for at least a further 24 hours. In case a patient received rescue medication before (fever) clearance, the time to event was censored at the first use of rescue medication.	Day 29
Secondary	Time to Recrudescence and Reinfection at Study Day 29	Time to recrudescence is calculated from the date of first study medication to the date of first event. Participants without recrudescence/reinfection after Day 7 are censored at the time of treatment failure or at the time of last parasite assessment if no treatment failure occured.	Day 29
Secondary	Maximum Peak Observed Concentration (Cmax)	Maximum Peak Observed Concentration (Cmax)	Day 1, Day 3
Secondary	Tmax	Tmax	Day 1, Day 3
Secondary	AUC0-24	AUC0-24	Day 1, Day 3
Secondary	Half-life (T^1/2)	Half-life (T^1/2)	Upto day 15 post dose

External Links

•   A Plain Language Trial Summary is available on novartisclinicaltrials.com