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To Evaluate Efficacy, Safety, Tolerability and PK of Intravenous Cipargamin in Participants With Severe Plasmodium Falciparum Malaria

NCT ID: NCT04675931

Last Updated: 2025-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

254 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-07

Study Completion Date

2025-08-20

Brief Summary

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The purpose of this study is to identify the safe and effective dose of intravenous cipargamin in participants with moderately severe and severe malaria.

The study also intends to evaluate clinical treatment success using a novel clinical endpoint for drug development in severe malaria.

Severe malaria is a medical emergency and is affecting primarily young children in Africa. Injectable artesunate is the standard of care for the treatment of severe malaria and is highly efficacious. However, the spread of artemisinin-resistance in Plasmodium falciparum in Asian countries poses a threat for future treatment of patients with this life-threatening disease. To mitigate this risk, there is a need of another drug in malaria endemic countries. Cipargamin treatment results in rapid clearance of parasites including artemisinin resistant parasites.

Detailed Description

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Conditions

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Severe Malaria

Keywords

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KAE609 cipargamin artesunate intravenous i.v. pediatric dose-finding safety tolerability pharmacokinetics

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

This will be an adaptive, multicenter, randomized, open label, sequential cohort study in participants aged ≥ 12 years old in Cohorts 1-2 and \< 12 years old to ≥ 6 months in Cohorts 3-5 with a diagnosis of moderately severe and severe P. falciparum malaria. In Cohorts 1-2, participants will get randomized to one of the three treatment arms (2 dose of intravenous cipargamin or intravenous artesunate - comparator ). After Cohort 2, interim analysis will be performed to take one best dose of intravenous cipargamin forward for Cohorts 3-5. Participants in Cohorts 3-5 with be randomized to one of two treatments arms ( intravenous cipargamin or intravenous artesunate - comparator).
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Although the study is open label however in order to minimize the potential impact of treatment knowledge, treatment allocation, dose information, PK/AAG assessment schedule and concentration data, as well as other data that may result in systematic unblinding will not be available to the Clinical Trial Team (CTT) (particularly clinicians, trial statisticians, trial programmers) until the database is locked after IA of Cohorts 1-2. After interim database lock, the CTT would be unblinded with the results, however, the blinding will then be continued for Cohorts 3-5 until the final database is locked.

Study Groups

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IV KAE609 Dose regimen 1

Intravenous KAE609 (cipargamin) 20 mg

Group Type EXPERIMENTAL

KAE609

Intervention Type DRUG

Two doses of Intravenous Cipargamin will be evaluated in the initial phase of the study (Cohorts 1-2).

These doses will cover a wider exposure range and facilitate the selection of an appropriate dose for later Cohorts 3-5.

IV KAE609 Dose regimen 2

Intravenous KAE609 (cipargamin) 40 mg

Group Type EXPERIMENTAL

KAE609

Intervention Type DRUG

Two doses of Intravenous Cipargamin will be evaluated in the initial phase of the study (Cohorts 1-2).

These doses will cover a wider exposure range and facilitate the selection of an appropriate dose for later Cohorts 3-5.

IV KAE609 Dose regimen 3

Intravenous KAE609 (cipargamin) Dose regimen 3 (dose will be evaluated post Interim analysis from Cohort 1 and Cohort 2.

Group Type EXPERIMENTAL

KAE609

Intervention Type DRUG

Two doses of Intravenous Cipargamin will be evaluated in the initial phase of the study (Cohorts 1-2).

These doses will cover a wider exposure range and facilitate the selection of an appropriate dose for later Cohorts 3-5.

IV Artesunate

IV Artesunate 2.4 mg/kg (for participants weighing at least 20 kg) IV Artesunate 3 mg/kg (for participants weighing less than 20 kg)

Group Type ACTIVE_COMPARATOR

IV Artesunate

Intervention Type DRUG

Parenteral artesunate is the WHO recommended first line treatment for severe malaria. Hence IV artesunate is used as comparator. Also, this will be used as rescue medication for participants where IV KAE609 is not working.

Coartem

Standard of care (Coartem) will be given to all participants for 3 days as part of treatment.

Group Type OTHER

Coartem

Intervention Type DRUG

Oral Standard of Care

Interventions

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KAE609

Two doses of Intravenous Cipargamin will be evaluated in the initial phase of the study (Cohorts 1-2).

These doses will cover a wider exposure range and facilitate the selection of an appropriate dose for later Cohorts 3-5.

Intervention Type DRUG

IV Artesunate

Parenteral artesunate is the WHO recommended first line treatment for severe malaria. Hence IV artesunate is used as comparator. Also, this will be used as rescue medication for participants where IV KAE609 is not working.

Intervention Type DRUG

Coartem

Oral Standard of Care

Intervention Type DRUG

Other Intervention Names

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Cipargamin Artesunate Artemether Lumefantrine

Eligibility Criteria

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Inclusion Criteria

* Cohort 1: Participants aged ≥ 12 years with moderately severe malaria as defined in (prostration and/or repeated vomiting) without presence of other signs of severe malaria (and with high P. falciparum parasitemia (60,000-250,000 parasites per µl)

* Subsequent Cohorts 2 to 5: Participants diagnosed with severe malaria as defined in modified version of WHO criteria and P. falciparum parasite count of ≥ 5000 per µl
* Cohort 2: Participants aged ≥ 12 years
* Cohort 3: Participants aged 6 - \< 12 years
* Cohort 4: Participants aged 2 - \< 6 years
* Cohort 5: Participants aged ≥ 6 months - \< 2 years

Exclusion Criteria

* Mixed Plasmodium infections
* Treatment with quinine or artemisinin derivative or any other antimalarial drug or any antibiotic with known antimalarial activity within 12 hours of screening.
* Signs/symptoms of severe malnutrition in general accordance with WHO guidelines:

1. Under 18 years: \<-3 Z-scores of WHO growth standard for weight-for-height/length (in children \< 5 years) or BMI for age (5-18 years), or very low mid-upper arm circumference (MUAC \< 115 mm in children \< 12 years, \< 160mm 12-18 years), or bilateral pitting edema
2. Over 18 years: BMI \< 16 kg/m2 or MUAC \< 160mm or bilateral pitting edema
* Known underlying illness, surgical or medical condition, which is not related to ongoing event of severe malaria and which might jeopardize the participant's health in case of participation in the study or which might alter the distribution, metabolism or excretion of study treatment. For example:

1. neurological or neurodegenerative disorders,
2. cardiac, renal, or hepatic disease, diabetes,
3. epilepsy, cerebral palsy,
4. known or suspected to be HIV-1 positive and/or receiving antiretroviral treatment
5. malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
6. known or suspected cases of active infections or concurrent febrile illness such as TB, Typhoid, COVID-19 etc.



* ALT \> 5 x the upper limit of normal range (ULN), regardless the level of total bilirubin
* Total bilirubin is \> 3 mg/dL
* Body weight of \< 35 kg or \>75 kg


* Body weight of \< 35 kg or \>75 kg
* Participants diagnosed as moderately severe malaria due to repeated vomiting without presence of any of the symptoms of severe malaria


* Body weight of \< 5 kg
* Participants diagnosed as moderately severe malaria due to repeated vomiting without presence of any of the symptoms of severe malaria
Minimum Eligible Age

6 Months

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Wellcome Trust

OTHER

Sponsor Role collaborator

European and Developing Countries Clinical Trials Partnership (EDCTP)

OTHER_GOV

Sponsor Role collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Burkina Faso, , Burkina Faso

Site Status

Novartis Investigative Site

Ouagadougou, , Burkina Faso

Site Status

Novartis Investigative Site

Abidjan, , Côte d’Ivoire

Site Status

Novartis Investigative Site

Agboville, , Côte d’Ivoire

Site Status

Novartis Investigative Site

Kinsasha, Democratic Republic of Congo, Democratic Republic of the Congo

Site Status

Novartis Investigative Site

Siaya, , Kenya

Site Status

Novartis Investigative Site

Manhiça, Maputo Province, Mozambique

Site Status

Novartis Investigative Site

Kigali, , Rwanda

Site Status

Novartis Investigative Site

Tororo, , Uganda

Site Status

Countries

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Gabon India Nigeria Republic of the Congo Tanzania Burkina Faso Côte d’Ivoire Democratic Republic of the Congo Kenya Mozambique Rwanda Uganda

Other Identifiers

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217692/Z/19/Z

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2020-005035-70

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CKAE609B12201

Identifier Type: -

Identifier Source: org_study_id