Health Condition 1: B508- Other severe and complicated Plasmodium falciparum malaria
Conditions
Interventions
Intervention1: KAE609 20 mg: Minimum of two doses
q24h (to be administered at 0 hour and 24 hours) and not exceeding three doses (Dose 3 at 48 hours) followed by oral medication (Coartem® bid for 3 days)
Intervention2: KAE609 40 mg: Minimum of two d
q24h (to be administered at 0 hour and 24 hours) and not exceeding three doses (Dose 3 at 48 hours) followed by oral medication (Coartem® bid for 3 days)
Control Intervention1: Artesunate 60 mg/vial:
Sponsors
Novartis Healthcare Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1. Cohort 1: Participants aged >= 12 years with moderately severe malaria as defined in Barnes et al 2004 (prostration and/or repeated vomiting) without presence of other signs of severe malaria (Section 16.4) 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 Section 16.4 (modified version of severe malaria criteria in WHO 2014) and P. falciparum parasite count of >= 5000 per μl Cohort 2: Participants aged >= 12 years Cohort 3: Participants aged 6 - Cohort 4: Participants aged 2 - Cohort 5: Participants aged >=6 months - 2. Written informed consent form must be obtained prior to any study related procedure. If the participant is unable to read and write or otherwise incapable of signing an informed consent, then a witnessed consent according to local ethical standards is permitted (formally documented and witnessed, ideally via an independent trusted witness). Participants aged with parental/legal guardian consent or as per local ethical guidelines. The participant or parent/legal guardian (in case of pediatric participants) is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions for their child and is likely to complete the study as planned.
Exclusion criteria
Exclusion criteria: 1 Mixed plasmodium infections 2 Treatment with any antimalarial drug (including quinine or artemisinin derivative) or any antibiotic with known antimalarial activity within 12 hours of screening 3 Known underlying illness, surgical or medical condition not related to ongoing episode of malaria which might jeopardize the patientâ??s health 4 Known or suspected case of active infections or concurrent febrile illness such as HIV, TB, Typhoid, COVID-19 etc. 5 Known h/o ECG abnormalities indicating significant risk to safety of participants-Clinically significant cardiac arrhythmias-H/o familial long QT syndrome or Torsades de Pointes-QTcF > 450 ms in males and QTcF > 460 ms in females aged >= 12 years old and QTcF > 450 ms in females aged 6 Severe malnutrition â?? In accordance with WHO guidelines 7 Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer 8 Participants taking prohibited medications as per protocol 9 Pregnant or nursing (lactating) women 10 Female of child bearing potential and sexually active males unless they are using one of the highly effective contraception methods (refer protocol section 5.2) during dosing and one week after last IV dose Exclusion criteria for Cohort 1: 1. ALT > 5 x the upper limit of normal range (ULN), regardless the level of total bilirubin 2. ALT > 3 x ULN and total bilirubin is > 3 mg/dL 3. Body weight of 75 kg Exclusion criteria for Cohort 2: 1. Body weight of 75 kg 2. 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: 1. Body weight of 2. Participants diagnosed as moderately severe malaria due to repeated vomiting without presence of any of the symptoms of severe malaria.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the efficacy of IV cipargaminTimepoint: Variable: A binary outcome indicating â?¥ 90% reduction in P. falciparum parasite at 12 hours (H12) after first IV dose as compared to baseline. | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess clinical outcomeTimepoint: Proportion of participants with clinical success over time. Clinical success at 48 hours is considered as the key secondary endpoint,for the secondary estimand.;To assess the presence/absence of individual signs of severe malariaTimepoint: Proportion of participants with individual signs of severe malaria over time;To assess the risk of hemolysisTimepoint: Proportion of participants developing hemolysis (early and delayed) after treatment;To assess the risk of long term neurological sequelaeTimepoint: Proportion of participants with neurological sequelae at Day 29;To evaluate parasite clearance dynamicsTimepoint: Proportions of participants with â?¥ 90% parasite reduction at 24 and 48 hours PCE slope half-life Time to P. falciparum parasite clearance (PCT) P. falciparum parasite reduction ratios (PRR) at 12, 24 and 48 hours Proportion of participants with recrudescence and reinfection by Day 29 | — |
Countries
Burkina Faso, Democratic Republic of the Congo, Gabon, India, Kenya, Malawi, Mozambique, Nigeria, Rwanda, Tanzania, Uganda
Contacts
Public ContactMurugananthan K
Novartis Healthcare PVTLTD
Outcome results
None listed