Clinical trial NCT02198807: Evaluation of Fosmidomycin and Piperaquine in the Treatment of Acute Falciparum Malaria
Official title: A Phase IIa Proof of Concept Study to Explore the Efficacy, Tolerability and Safety of Fosmidomycin Sodium When Administered With Piperaquine Tetraphosphate to Adults and Older Children With Acute Uncomplicated Plasmodium Falciparum Malaria
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Oral Treatment of Acute Uncomplicated Plasmodium Falciparum Malaria
Lead sponsor: Jomaa Pharma GmbH
Sponsor class: INDUSTRY
Collaborators: name: Centre de Recherche Médicale de Lambaréné
First posted: 2014-07-24
Enrollment: 100
Sex: ALL
Minimum age (years): 1
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this study is to explore the role of fosmidomycin and piperaquine as non-artemisinin-based combination therapy for acute uncomplicated Plasmodium falciparum when administered over three days.

Together, fosmidomycin and piperaquine fulfil the WHO criteria for combination therapy by meeting the three key parameters of having different modes of action and different biochemical targets while exhibiting independent blood schizonticidal activity. Like the artemisinins, fosmidomycin is fast-acting, has an excellent safety record and is active against existing drug-resistant parasites. Piperaquine has a long half life protecting fosmidomycin as a much shorter lived molecule against selection of resistant parasites and will provide post-treatment prophylaxis.


Eligibility criteria: Inclusion Criteria:

* Male and female subjects aged 1 to 60 years inclusive
* Body weight between 5kg and 90kg inclusive
* Acute manifestations of a mono-infection with Plasmodium falciparum as determined by either a rapid diagnostic test for adults or microscopically confirmed by an asexual parasitaemia of 1,000 to 150,000/uL and fever with an axillary temperature of \> 37.5 degress C or oral/rectal/tympanic temperature of \> 38.0 degrees C or history of fever during the previous 72 hours
* Compliance with contraceptive measures throughout the study period of 63 days in females of child bearing potential

Exclusion Criteria:

To be eligible for inclusion in the study, subjects must NOT meet any of the following criteria:

* Signs of severe/complicated malaria according to WHO criteria
* Pregnancy as excluded by negative serum human chorionic gonadotrophin (hCG) test
* Lactation
* Mixed Plasmodium infection
* Severe vomiting on three or more occasions in the previous 24 hours
* Severe diarrhoea on four or more occasions in the previous 24 hours
* Concomitant disease masking assessment of response including

  * abnormal liver function tests with bilirubin \> 40 µmol/L, aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) levels \> x 2 upper limit of normal
  * impaired renal function with creatinine level \> x 2 upper limit of normal
  * haemoglobin level \< 7.5g/dl
  * white cell count \> 12000/µL
* History of cardiovascular disease including arrhythmia with QTc interval ≥ 450msec, respiratory disease including active tuberculosis, hepatic disease including jaundice, renal failure, malignancy, neurological disorders including convulsions and psychiatric disturbances
* History of immunological disease including Hepatitis A, B and C and HIV-AIDS
* Severe malnutrition
* History of hypersensitivity or adverse reactions to fosmidomycin, piperaquine, artesunate and mefloquine
* Treatment with antimalarial and antibacterial agents within the previous 28 days

Primary outcomes:
measure: Per protocol, PCR-corrected cure rate on Day 28
timeFrame: 28 days
Secondary outcomes:
measure: Per protocol, PCR-corrected cure rates on Day 7 and Day 63
timeFrame: 63 days
measure: Derived parasite reduction ratio at 48 hours
timeFrame: 2 days
measure: Parasite clearance time
timeFrame: 96 hours
measure: Fever clearance time
timeFrame: 96 hours
measure: Proportion of subjects with gametocytes on Day 7
timeFrame: 7 days
measure: Adverse event recording
timeFrame: 28 days
Other outcomes:
Locations:
Study officials:
References:
citation: Mombo-Ngoma G, Remppis J, Sievers M, Zoleko Manego R, Endamne L, Kabwende L, Veletzky L, Nguyen TT, Groger M, Lotsch F, Mischlinger J, Flohr L, Kim J, Cattaneo C, Hutchinson D, Duparc S, Moehrle J, Velavan TP, Lell B, Ramharter M, Adegnika AA, Mordmuller B, Kremsner PG. Efficacy and Safety of Fosmidomycin-Piperaquine as Nonartemisinin-Based Combination Therapy for Uncomplicated Falciparum Malaria: A Single-Arm, Age De-escalation Proof-of-Concept Study in Gabon. Clin Infect Dis. 2018 Jun 1;66(12):1823-1830. doi: 10.1093/cid/cix1122.