Phase 2
N=254
To Evaluate Efficacy, Safety, Tolerability and PK of Intravenous Cipargamin in Participants With Severe Plasmodium Falciparum Malaria
Severe Malaria
Bottom Line
View on ClinicalTrials.gov: NCT04675931 ↗Enrolled (actual)
254
Serious AEs
3.6%
Results posted
Apr 2026
Primary outcome: Primary: Percentage of Participants Achieving at Least 90% Reduction in Plasmodium Falciparum (P. Falciparum) at 12 Hours — 80.0; 93.0; 39.3 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Cipargamin (Drug); IV Artesunate (Drug); Coartem (Drug)
- Age
- Pediatric, Adult, Older Adult · 0+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Jul 2025
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Achieving at Least 90% Reduction in Plasmodium Falciparum (P. Falciparum) at 12 Hours |
80.0; 93.0; 39.3 | — |
| SECONDARY Percentage of Participants Achieving Clinical Success at 48 Hours |
95.0; 85.1; 74.4 | — |
| SECONDARY Percentage of Participants With Individual Signs of Severe Malaria Over Time |
95.0; 98.2; 100.0; 35.0; 43.9; 45.3 | — |
| SECONDARY Percentage of Participants Developing Hemolysis (Early and Delayed) After Treatment |
55.0; 54.4; 62.1; 5.0; 3.5; 3.4 | — |
| SECONDARY Percentage of Participants With Neurological Sequelae at Day 29 |
0; 0; 0.9; 0; 0; 0.9 | — |
| SECONDARY Percentage of Participants Achieving at Least 90% Reduction in Plasmodium Falciparum (P. Falciparum) |
90.0; 100.0; 97.4; 100.0; 100.0; 99.1 | — |
| SECONDARY Time to Parasite Clearance (PCT) |
21.1; 18.0; 36.0 | — |
| SECONDARY Parasite Clearance Estimator (PCE) Slope Half-life |
1.63; 1.10; 2.21 | — |
| SECONDARY Time to Fever Clearance (FCT) |
6.2; 6.1; 17.8 | — |
| SECONDARY P. Falciparum Parasite Reduction Ratios (PRR) at 12, 24 and 48 Hours |
203.2; 1347.8; 7.5; 3772.6; 4092.5; 560.6 | — |
| SECONDARY Percentage of Participants With Recrudescence and Reinfection |
0; 2.7; 1.8; 0; 8.0; 7.9 | — |
| SECONDARY Time to Switch to Oral Therapy |
43.9; 43.3; 44.4 | — |
| SECONDARY Time to Discharge From Hospital |
73.2; 73.1; 73.1 | — |
| SECONDARY Time to Recover From Prostration |
18.2; 12.4; 18.3 | — |
| SECONDARY Number of Participants With Adverse Events or Serious Adverse Events, or Who Died |
12; 79; 73; 0; 5; 4 | — |
| SECONDARY Observed Maximum Plasma Concentration (Cmax) of IV Cipargamin |
1350; 3230; 1390; 3420; 1160; 2720 | — |
| SECONDARY Time of Maximum Observed Drug Concentration Occurrence (Tmax) of IV Cipargamin |
0.099; 0.106; 0.221; 0.158; 0.141; 0.05 | — |
| SECONDARY Area Under the Serum Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of IV Cipargamin |
8150; 18800; 19100; 38700; 18600; 40400 | — |
| SECONDARY Area Under the Concentration Time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUCinf) of IV Cipargamin |
21300; 40000; 18800; 40400 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From the Time 0 to 24 Hours (AUC0-24hours) of IV Cipargamin |
8170; 19200; 11900; 28500; 10100; 26500 | — |
| SECONDARY Terminal Elimination Half Life (T1/2) of IV Cipargamin |
18; 11.6; 16.2; 10.8 | — |
| SECONDARY Total Systemic Clearance for Intravenous Administration (CL) of IV Cipargamin |
0.939; 0.66; 1.06; 0.99 | — |
| SECONDARY Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) of IV Cipargamin |
24.5; 11; 24.9; 15.5 | — |
Summary
The purpose of this study was to identify the safe and effective dose of intravenous cipargamin in participants with moderately severe and severe malaria.
The study also intended 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 for another drug in malaria-endemic countries. Cipargamin treatment results in rapid clearance of parasites, including artemisinin-resistant parasites.
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 - 5 x the upper limit of normal range (ULN), regardless the level of total bilirubin
- Total bilirubin is > 3 mg/dL
- Body weight of 75 kg
Exclusion criteria for Cohort 2:
- Body weight of 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
Data sourced from ClinicalTrials.gov (NCT04675931). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.