search
Back to results

Evaluation of Fosmidomycin and Piperaquine in the Treatment of Acute Falciparum Malaria (FOSPIP)

Primary Purpose

Oral Treatment of Acute Uncomplicated Plasmodium Falciparum Malaria

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Fosmidomycin-Piperaquine
Sponsored by
Jomaa Pharma GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oral Treatment of Acute Uncomplicated Plasmodium Falciparum Malaria

Eligibility Criteria

1 Year - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Fosmidomycin-Piperaquine

    Arm Description

    Fosmidomycin sodium capsules 450 mg, dosage: 30mg/kg twice daily for 3 days Piperaquine phosphate tablets 320 mg, dosage: 16 mg/kg once a day for 3 days

    Outcomes

    Primary Outcome Measures

    Per protocol, PCR-corrected cure rate on Day 28
    Six-hourly asexual counts until negative on three successive occasions. Weekly smears on days 7, 14, 21 and 28

    Secondary Outcome Measures

    Per protocol, PCR-corrected cure rates on Day 7 and Day 63
    Weekly smears on days 35 +/- 3 days, 42 +/- 3 days and 63 +/- 3 days
    Derived parasite reduction ratio at 48 hours
    Six-hourly asexual counts until negative on three successive occasions
    Parasite clearance time
    Six-hourly asexual counts until negative on three successive occasions
    Fever clearance time
    Six hourly temperature recordings until normal on three successisve occasions
    Proportion of subjects with gametocytes on Day 7
    Smear on Day 7
    Adverse event recording
    Recording of vital signs and ECG monitoring Recording of incidence, severity, drug-relatedness and seriousness of AEs and laboratory abnormalites

    Full Information

    First Posted
    July 22, 2014
    Last Updated
    June 12, 2015
    Sponsor
    Jomaa Pharma GmbH
    Collaborators
    Centre de Recherche Médicale de Lambaréné
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT02198807
    Brief Title
    Evaluation of Fosmidomycin and Piperaquine in the Treatment of Acute Falciparum Malaria
    Acronym
    FOSPIP
    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

    2. Study Status

    Record Verification Date
    June 2015
    Overall Recruitment Status
    Unknown status
    Study Start Date
    March 2014 (undefined)
    Primary Completion Date
    July 2014 (Actual)
    Study Completion Date
    December 2015 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Jomaa Pharma GmbH
    Collaborators
    Centre de Recherche Médicale de Lambaréné

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Oral Treatment of Acute Uncomplicated Plasmodium Falciparum Malaria

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    100 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Fosmidomycin-Piperaquine
    Arm Type
    Experimental
    Arm Description
    Fosmidomycin sodium capsules 450 mg, dosage: 30mg/kg twice daily for 3 days Piperaquine phosphate tablets 320 mg, dosage: 16 mg/kg once a day for 3 days
    Intervention Type
    Drug
    Intervention Name(s)
    Fosmidomycin-Piperaquine
    Primary Outcome Measure Information:
    Title
    Per protocol, PCR-corrected cure rate on Day 28
    Description
    Six-hourly asexual counts until negative on three successive occasions. Weekly smears on days 7, 14, 21 and 28
    Time Frame
    28 days
    Secondary Outcome Measure Information:
    Title
    Per protocol, PCR-corrected cure rates on Day 7 and Day 63
    Description
    Weekly smears on days 35 +/- 3 days, 42 +/- 3 days and 63 +/- 3 days
    Time Frame
    63 days
    Title
    Derived parasite reduction ratio at 48 hours
    Description
    Six-hourly asexual counts until negative on three successive occasions
    Time Frame
    2 days
    Title
    Parasite clearance time
    Description
    Six-hourly asexual counts until negative on three successive occasions
    Time Frame
    96 hours
    Title
    Fever clearance time
    Description
    Six hourly temperature recordings until normal on three successisve occasions
    Time Frame
    96 hours
    Title
    Proportion of subjects with gametocytes on Day 7
    Description
    Smear on Day 7
    Time Frame
    7 days
    Title
    Adverse event recording
    Description
    Recording of vital signs and ECG monitoring Recording of incidence, severity, drug-relatedness and seriousness of AEs and laboratory abnormalites
    Time Frame
    28 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    1 Year
    Maximum Age & Unit of Time
    60 Years
    Accepts Healthy Volunteers
    No
    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

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    29293893
    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.
    Results Reference
    derived

    Learn more about this trial

    Evaluation of Fosmidomycin and Piperaquine in the Treatment of Acute Falciparum Malaria

    We'll reach out to this number within 24 hrs