Severe Plasmodium falciparum Malaria MedDRA version: 26.0 Level: PT Classification code 10069722 Term: Complicated malaria System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Coartem
Product Name: Coartem
Product Code: COA566
Pharmaceutical Form: Tablet
INN or Proposed INN: Lumefantrine
CAS Number: 82186-77-4
Concentration unit: mg milligram(s)
Concentration ty
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants eligible for inclusion in this study must meet all of the following 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 - =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Participants meeting any of the following criteria are not eligible for inclusion in this study. 1. Exclusion criteria applying to all Cohorts 1 to 5: 1. Mixed Plasmodium infections 2. Treatment with quinine or artemisinin derivative or any other antimalarial drug or any antibiotic with known antimalarial activity within 12 hours of screening 3. 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, e.g. : • 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. 4. Known history of ECG abnormalities indicating significant risk of safety for participants such as: a. Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker b. History of familial long QT syndrome or known family history of Torsades de Pointes c. QTcF > 450 ms in males and QTcF > 460 ms in females aged = 12 years old and QTcF > 450 ms in females aged < 12 years. 5. 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 6. Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations 7. Participants taking prohibited medication defined as per Section 6.2.3 8. Pregnant or nursing (lactating) women 9. Female of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective contraception methods (listed below) during dosing and until one week after last IV dose or until start of next menstruation after last dose of oral standard of care (Coartem), whichever is later. Required highly effective contraception methods include: a. Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Periodic abstinence (i.e., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception b. Male partner sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that participant c. Female sterilization (have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To assess the efficacy of IV cipargamin;Secondary Objective: •To assess clinical outcome •To assess the presence/absence of individual signs of severe malaria •To assess the risk of hemolysis •To assess the risk of long term neurological sequelae •To evaluate parasite clearance dynamics •To assess other efficacy endpoints •To evaluate the safety and tolerability of IV cipargamin •To assess the plasma pharmacokinetics of IV cipargamin ;Primary end point(s): •Proportion of participants with = 90% P. falciparum parasite reduction at 12 hours;Timepoint(s) of evaluation of this end point: 12 hours | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Proportion of participants with clinical success over time. Clinical success at 48 hours is considered as the key secondary endpoint • Proportion of participants with individual signs of severe malaria over time • Proportion of participants developing hemolysis (early and delayed) after treatment • Proportion of participants with neurological sequelae at Day 29 • Proportions of participants with = 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 • Time (days and hours) to switch to oral therapy Day of discharge from hospital, Time (hours) to recover from prostration • Standard safety/tolerability assessments (incidence of serious adverse events (SAEs), mortality, in-hospital mortality, adverse events (AEs), and routine safety and laboratory assessments) • PK parameters of cipargamin: Cmax, T1/2, AUC, CL and Vz Alpha-1-acid glycoprotein level over time and correlation of AAG concentration with cipargamin PK parameters ;Timepoint(s) of evaluation of this end point: See above section E.5.2 | — |
Countries
Burkina Faso, Congo, The Democratic Republic of the, Côte d’Ivoire, Gabon, India, Kenya, Mozambique, Nigeria, Rwanda, Tanzania, United Republic of, Uganda
Contacts
Public ContactClinical Disclosure Office
Novartis Pharma AG
Outcome results
None listed