Safety of KAE609 in Adults With Uncomplicated Plasmodium Falciparum Malaria.

Novartis

Status and phase: Completed; Phase 2

Conditions: Malaria

Treatments: Drug: KAE609; Drug: Coartem

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT03334747

CKAE609A2202

207813/Z/17/Z (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Enrollment: 188 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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188 participants in 9 patient groups

Treatment arm 1: KAE609 10 mg Single Dose (SD)

Experimental group

Description:

KAE609 10 mg once daily (QD) for 1 day

Treatment:

Drug: KAE609

Treatment arm 2:KAE609 25 mg SD

Experimental group

Description:

KAE609 25 mg once daily (QD) for 1 day

Treatment:

Drug: KAE609

Treatment arm 3:KAE609 10 mg 3 Days

Experimental group

Description:

KAE609 10 mg (QD) for 3 days

Treatment:

Drug: KAE609

Treatment arm 4:KAE609 50 mg SD

Experimental group

Description:

KAE609 50 mg once daily (QD) for 1 day

Treatment:

Drug: KAE609

Treatment arm 5:KAE609 25 mg 3 Days

Experimental group

Description:

KAE609 25 mg once daily (QD) for 3 days

Treatment:

Drug: KAE609

Treatment arm 6:KAE609 75 mg SD

Experimental group

Description:

KAE609 75 mg once daily (QD) for 1 day

Treatment:

Drug: KAE609

Treatment arm 7:KAE609 50 mg 3 Days

Experimental group

Description:

KAE609 50 mg once daily (QD) for 3 days

Treatment:

Drug: KAE609

Treatment arm 8: KAE609 150 mg SD

Experimental group

Description:

KAE609 150 mg once daily (QD) for 1 day

Treatment:

Drug: KAE609

Treatment arm 9: Coartem Control

Active Comparator group

Description:

Coartem® control

Treatment:

Drug: Coartem