NCT03334747

Brief 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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
188

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Nov 2017

Geographic Reach
5 countries

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 27, 2017

Completed
11 days until next milestone

First Posted

Study publicly available on registry

November 7, 2017

Completed
9 days until next milestone

Study Start

First participant enrolled

November 16, 2017

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 23, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 23, 2019

Completed
10 months until next milestone

Results Posted

Study results publicly available

September 25, 2020

Completed
Last Updated

October 11, 2021

Status Verified

October 1, 2021

Enrollment Period

2 years

First QC Date

October 27, 2017

Results QC Date

September 3, 2020

Last Update Submit

October 7, 2021

Conditions

Malaria

Keywords

uncomplicated Plasmodium falciparum Malaria.

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (8)

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

    Day 15, Day 29

  • Parasite Clearance Time (PCT)

    Day 29

  • Fever Clearance Time (FCT)

    Day 29

  • Time to Recrudescence and Reinfection at Study Day 29

    Day 29

  • Maximum Peak Observed Concentration (Cmax)

    Day 1, Day 3

  • +3 more secondary outcomes

Study Arms (9)

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

EXPERIMENTAL

KAE609 10 mg once daily (QD) for 1 day

Drug: KAE609

Treatment arm 2:KAE609 25 mg SD

EXPERIMENTAL

KAE609 25 mg once daily (QD) for 1 day

Drug: KAE609

Treatment arm 3:KAE609 10 mg 3 Days

EXPERIMENTAL

KAE609 10 mg (QD) for 3 days

Drug: KAE609

Treatment arm 4:KAE609 50 mg SD

EXPERIMENTAL

KAE609 50 mg once daily (QD) for 1 day

Drug: KAE609

Treatment arm 5:KAE609 25 mg 3 Days

EXPERIMENTAL

KAE609 25 mg once daily (QD) for 3 days

Drug: KAE609

Treatment arm 6:KAE609 75 mg SD

EXPERIMENTAL

KAE609 75 mg once daily (QD) for 1 day

Drug: KAE609

Treatment arm 7:KAE609 50 mg 3 Days

EXPERIMENTAL

KAE609 50 mg once daily (QD) for 3 days

Drug: KAE609

Treatment arm 8: KAE609 150 mg SD

EXPERIMENTAL

KAE609 150 mg once daily (QD) for 1 day

Drug: KAE609

Treatment arm 9: Coartem Control

ACTIVE COMPARATOR

Coartem® control

Drug: Coartem

Interventions

KAE609DRUG

Exploration of different doses of KAE609 to establish safety profile.

Also known as: Cipargamin
Treatment arm 1: KAE609 10 mg Single Dose (SD)Treatment arm 2:KAE609 25 mg SDTreatment arm 3:KAE609 10 mg 3 DaysTreatment arm 4:KAE609 50 mg SDTreatment arm 5:KAE609 25 mg 3 DaysTreatment arm 6:KAE609 75 mg SDTreatment arm 7:KAE609 50 mg 3 DaysTreatment arm 8: KAE609 150 mg SD
CoartemDRUG

Control Arm

Also known as: Artemether Lumefantrine
Treatment arm 9: Coartem Control

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Novartis Investigative Site

Lambaréné, Gabon

Location

Novartis Investigative Site

Kintampo, Ghana

Location

Novartis Investigative Site

Navrango, Ghana

Location

Novartis Investigative Site

Bamako, Mali

Location

Novartis Investigative Site

Sotouba, Mali

Location

Novartis Investigative Site

Kigali, Rwanda

Location

Novartis Investigative Site

Bushenyi, Uganda

Location

Novartis Investigative Site

Kampala, Uganda

Location

Novartis Investigative Site

Tororo, Uganda

Location

Related Publications (2)

  • Ndayisaba G, Yeka A, Asante KP, Grobusch MP, Karita E, Mugerwa H, Asiimwe S, Oduro A, Fofana B, Doumbia S, Jain JP, Barsainya S, Kullak-Ublick GA, Su G, Schmitt EK, Csermak K, Gandhi P, Hughes D. Hepatic safety and tolerability of cipargamin (KAE609), in adult patients with Plasmodium falciparum malaria: a randomized, phase II, controlled, dose-escalation trial in sub-Saharan Africa. Malar J. 2021 Dec 20;20(1):478. doi: 10.1186/s12936-021-04009-1.

    PMID: 34930267DERIVED

  • Schmitt EK, Ndayisaba G, Yeka A, Asante KP, Grobusch MP, Karita E, Mugerwa H, Asiimwe S, Oduro A, Fofana B, Doumbia S, Su G, Csermak Renner K, Venishetty VK, Sayyed S, Straimer J, Demin I, Barsainya S, Boulton C, Gandhi P. Efficacy of Cipargamin (KAE609) in a Randomized, Phase II Dose-Escalation Study in Adults in Sub-Saharan Africa With Uncomplicated Plasmodium falciparum Malaria. Clin Infect Dis. 2022 May 30;74(10):1831-1839. doi: 10.1093/cid/ciab716.

    PMID: 34410358DERIVED

Related Links

MeSH Terms

Conditions

Malaria

Interventions

NITD 609Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

ArtemetherArtemisininsReactive Oxygen SpeciesFree RadicalsInorganic ChemicalsOrganic ChemicalsLumefantrineFluorenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSesquiterpenesTerpenesPolycyclic CompoundsDrug CombinationsPharmaceutical Preparations

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals
Novartis.email@novartis.com
862-778-8300

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Patients were randomized to KAE609 and Coartem in parallel treatment arms. Increasing doses of KAE609 (single dose and multiple dose) were evaluated in dose escalated manner in sequential cohorts
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 27, 2017

First Posted

November 7, 2017

Study Start

November 16, 2017

Primary Completion

November 23, 2019

Study Completion

November 23, 2019

Last Updated

October 11, 2021

Results First Posted

September 25, 2020

Record last verified: 2021-10

Data Sharing

IPD Sharing
Will share

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Locations

RW(1)GA(1)GH(2)UG(3)MA(2)