To Evaluate Efficacy, Safety, Tolerability and PK of Intravenous Cipargamin in Participants With Severe Plasmodium Falciparum Malaria - KAE609B12201(KARISMA)

Phase 2

• Conditions: Malaria

• Registration Number: PACTR202102626263606
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-22
• Last Update Posted: 29 May 2023

Recruitment & Eligibility

• Status: Pending
• Sex: All
• Target Recruitment: 252

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

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 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.

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

for Cohort 2:
- Body weight of < 35 kg or >75 kg
- moderately severe malaria due to repeated vomiting without presence of any of the symptoms of severe malaria

for Cohorts 3 to 5:
- Body weight of < 5 kg
- moderately severe malaria due to repeated vomiting without presence of any of the symptoms of severe malaria

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Percentage of participants achieving at least 90% reduction in Plasmodium falciparum (P. falciparum) at 12 hours [ Time Frame: Day 1 (12 Hours) ]<br>A blood draw will be performed at each collection time point for parasitemia assessment.