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

An Adaptive, Randomized, Active-controlled, Open-label, Sequential Cohort, Multicenter Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Intravenous Cipargamin (KAE609) in Adult and Pediatric Participants With Severe Plasmodium Falciparum Malaria (KARISMA - KAE609's Role In Severe Malaria)

ClinicalTrials.gov Identifier: NCT04675931

Novartis Reference Number: CKAE609B12201

Last Update: May 17, 2022

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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.

Condition 
Severe Malaria
Phase 
Phase 2
Overall status 
Recruiting
Start date 
Mar 07, 2022
Completion date 
Feb 26, 2024
Gender 
All
Age(s)
6 Years and older (Child, Adult, Older Adult)

Interventions

Drug
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.
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.
Drug
Coartem
Oral Standard of Care

Eligibility Criteria

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:

Exclusion criteria applying to all Cohorts 1 to 5:

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:

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
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:

neurological or neurodegenerative disorders,
cardiac, renal, or hepatic disease, diabetes,
epilepsy, cerebral palsy,
known or suspected to be HIV-1 positive and/or receiving antiretroviral treatment
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
known or suspected cases of active infections or concurrent febrile illness such as TB, Typhoid, COVID-19 etc.

Additional exclusion criteria are as follows:

Exclusion criteria for Cohort 1:

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

Exclusion criteria for Cohort 2:

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

Exclusion criteria for Cohorts 3 to 5:

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

Study Locations

Congo, The Democratic Republic of the
Novartis Investigative Site
Recruiting
Kinshasa, BP 7948
-
Congo, The Democratic Republic of the
Nigeria
Novartis Investigative Site
Recruiting
Ilorin,
-
Nigeria
Rwanda
Novartis Investigative Site
Recruiting
Kigali, BP 4560
-
Rwanda

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 

Have a question?

Call 1-888-669-6682 or email [email protected]