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Completed

NCT Number: NCT03334747

Safety of KAE609 in Adults With Uncomplicated Plasmodium Falciparum Malaria.

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site, Lambaréné, Gabon

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

KEY Inclusion Criteria:

  • Male and female patients ≥ 18 years with a body weight ≥ 45 kg.
  • Microscopic confirmation of acute uncomplicated P. falciparum using by Giemsa-stained thick film.
  • P. falciparum parasitaemia of 500 to 50 000 parasites/µL.
  • Axillary temperature ≥ 37.5ºC or oral/tympanic/rectal temperature ≥ 38.0ºC; or history of fever during the previous 24 hours.
  • 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:

  • Mixed Plasmodium infections.
  • Signs and symptoms of severe malaria according to World Health Organization (WHO) 2016 criteria (WHO 2016).
  • 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.
  • Clinical or laboratory evidence of any of the following:
  • AST/ALT > 1.5 x the upper limit of normal range (ULN), regardless of the level of total bilirubin
  • AST/ALT > 1.0 and ≤ 1.5 x ULN and total bilirubin is > ULN
  • Total bilirubin > 2 x ULN, regardless of the level of AST/ALT
  • History of photodermatitis/increased sensitivity to sun.
  • Pregnant or nursing (lactating) women.
  • Known disturbances of electrolyte balance, e.g. hypokalemia, hypocalcemia or hypomagnesemia.
  • Moderate to severe anemia (Hemoglobin level <8 g/dL).

Other protocol-defined inclusion/exclusion criteria may apply

Treatment and study plan

KAE609

Drug

Exploration of different doses of KAE609 to establish safety profile.

Other names: Cipargamin

Coartem

Drug

Control Arm

Other names: Artemether Lumefantrine

Primary outcomes

  1. Number of Participants With at Least 2 CTCAE Grades Increase From Baseline in Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST)

    Time frame: Day 29

    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.

Secondary outcomes

  1. Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected and Uncorrected Adequate Clinical and Parasitological Response (ACPR) at Day 15 and Day 29

    Time frame: Day 15, 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.

  2. Parasite Clearance Time (PCT)

    Time frame: Day 29

    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.

  3. Fever Clearance Time (FCT)

    Time frame: Day 29

    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.

  4. Time to Recrudescence and Reinfection at Study Day 29

    Time frame: 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.

  5. Maximum Peak Observed Concentration (Cmax)

    Time frame: Day 1, Day 3

    Maximum Peak Observed Concentration (Cmax)

  6. Tmax

    Time frame: Day 1, Day 3

    Tmax

  7. AUC0-24

    Time frame: Day 1, Day 3

    AUC0-24

  8. Half-life (T^1/2)

    Time frame: Upto day 15 post dose

    Half-life (T^1/2)

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Collaborators

  • Wellcome Trust

Registry information

Official study 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.

Important dates

Study start
2017
Primary completion
2019
Study completion
2019
First posted
Nov 7, 2017
Registry last updated
Oct 11, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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