Sevuparin/DF02 as an Adjunctive Therapy in Subjects Affected With Uncomplicated Falciparum Malaria

Study Overview
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Brief Summary
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The purpose of this study is to determine the tolerability and pharmacokinetics of Sevuparin/DF02 when administered as an i.v. infusion in combination with Malanil® (atovaquone/proguanil) as anti-malarial treatment in subjects affected with uncomplicated malaria. The study will also assess the potential of Sevupatin/DF02 to reduce infected erythrocyte sequestration and rosette formation. The study consists of a dose escalation part (part 1) followed by an open labelled, randomized comparison of treatment with Sevuparin/DF02 and Malanil® versus Malanil® alone (part 2).

Official Title
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A Phase I/II, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study of Sevuparin/DF02, as an Adjunctive Therapy in Subjects Affected With Uncomplicated Falciparum Malaria

Conditions
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Malaria, Falciparum

Intervention / Treatment
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* Drug: Sevuparin sodium + atovaquone/proquanil
* Drug: atovaquone/proquanil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presence of acute uncomplicated P. falciparum malaria, confirmed by positive blood smear with asexual forms of a single species (P. falciparum) Counts of asexual forms of P. falciparum: 10 000- 100 000/ul with or without gametocytaemia Presence of fever defined as > 38°C tympanic temperature or a history of fever within the last 24 hours Exclusion Criteria: Mixed infection with other Plasmodium species Any criteria of severe or complicated malaria as defined by the WHO, 2010 Use of high doses aspirin (more than 100 mg/day) or dual anti-platelet therapy or use of heparin,Low Molecular Weight Heparin (LMWH) or warfarin Presence of significant anemia as defined by Hb <8 g/dL or Hct < 25% A platelet count < 50,000/μL Presence of febrile conditions caused by diseases other than malaria

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sevuparin/DF02<br>Sevuparin/DF02 plus anti-malarial regimen (Malanil®) | Drug: Sevuparin sodium + atovaquone/proquanil<br>* Sevuparin 4 times per day and malanil according to label<br>|
| Active Comparator: Control<br>Anti-malarial regimen (Malanil®) alone | Drug: atovaquone/proquanil<br>* malanil according to label<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicities according to specified criteria |  | During treatment and 14 days post treatment follow-up. | 
| Area under the curve of late stage peripheral blood parasitemia over time (Part 2). |  | 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uncomplicated Falciparum Malaria, Plasmodium falciparum, Antimalarial treatment, Sevuparin/DF02, Adjuvant therapy, Malanil, Peripheral blood parasitemia, Rosette formation, Maximum tolerated dose