DSM265 Phase IIa Investigation Treating Plasmodium Falciparum or Vivax

June 21, 2016 updated by: Medicines for Malaria Venture

A Proof-of-Concept, Open Label Study to Assess the Efficacy, Safety, Tolerability and Pharmacokinetics of Single Doses of DSM265 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-Infection Over a 35-Day-Extended Observation Period

This will be a Proof-of-concept / Phase IIa, open label study to examine the efficacy of DSM265 in uncomplicated Plasmodium vivax and Plasmodium falciparum blood-stage malaria in adult patients. A minimum of two cohorts (20 patients) and a maximum of 6 cohorts (60 patients, 3 dose levels) will be tested. The starting dose of DSM265 for the first P. vivax and P. falciparum cohorts will be 400 mg. This dose is expected to show complete clearance of parasites by microscopy by Day 7 and a decrease in recrudescence rate assessed at Day 14 (success criteria for dose de-escalation and continuation of the study).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
45

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Peru
    • Departamento de Loreto (Amazonía Peruana)
      • Iquitos, Departamento de Loreto (Amazonía Peruana), Peru
        • Clínica de la Asociación Civil Selva Amazónica

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 56 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Body weight between 45kg and 90kg

  • Mono-infection of P. falciparum or P. vivax confirmed by:

    1. Fever, or history of fever in the previous 24 hours and,
    2. Microscopically confirmed parasite infection: 1,000 to 35,000 asexual parasite count/µL blood
  • Written informed consent
  • Able to swallow oral medication
  • Able and willing to participate and to comply with the study requirements
  • Agree to hospitalisation for at least 72 hours and until malarial parasites are not detected by microscopy on 2 consecutive occasions
  • Agree to return to clinic on Day 5 (in addition to the other study days), if by Day 3 malarial parasites have not fallen below level of detection on at least two consecutive occasions. If there are no longer any signs or symptoms of malaria then to be available every 3-4 days for blood sampling for microscopy and Quantitative Polymerase Chain Reaction, and re-hospitalisation for standard treatment in the event of levels being detectable

Exclusion Criteria:

  • Signs and symptoms of severe / complicated malaria according to the World Health Organisation Criteria 2010
  • Mixed Plasmodium infection
  • Severe vomiting, (more than three times in the 24 hours prior to inclusion) or inability to tolerate oral treatment, or severe diarrhoea
  • Presence of other serious or chronic clinical condition requiring hospitalisation
  • Severe malnutrition
  • Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, QTcB or QTcF interval greater than or equal to 450 msec, personal or family history of long QT syndrome, PR interval >200msec; any degree of heart block), respiratory (including active tuberculosis), history of jaundice, hepatic, renal, gastrointestinal, immunological, neurological (including auditory), endocrine including any type of diabetes mellitus (controlled or not), diabetes insipidus, uncontrolled hypo- or hyperthyroidism, endocrine reproductive disorders not requiring concurrent medication, disorders of adrenal function, infectious conditions other than minor skin or soft tissue infections or confirmed lower urinary tract infection, malignancy, psychiatric, history of convulsions or other neurological or psychiatric abnormality; any other disorder or condition that may render the patient unfit for participation or place him/her at increased risk
  • Known active Hepatitis A, Hepatitis B or Hepatitis C antibody

  • Any antimalarial treatment in the past:

    • a piperaquine-based compound, mefloquine, naphthoquine or sulphadoxine / pyrimethamine in the previous 6 weeks
    • amodiaquine or chloroquine in the previous 4 weeks
    • quinine, halofantrine, lumefantrine-based compounds and any other anti-malarial treatment or antibiotics with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones, and azithromycin) in the past 14 days
    • any herbal products or traditional medicines, in the past 7 days
  • Have received antibacterial treatment with known antimalarial activity in the preceding 14 days
  • Have received an investigational drug in the 4 weeks prior to screening
  • (a) Aspartate Aminotransferase / Alanine Aminotransferase at least twice the upper limit of normal range and total bilirubin is normal (b) Aspartate Aminotransferase / Alanine Aminotransferase more than 1.5 times the upper limit of normal range and total bilirubin is greater than 1 and less than or equal to 1.5 times the upper limit of normal range
  • Hemoglobin level less than or equal to 8g/dL
  • Total bilirubin greater than 1.5 times the upper limit of normal range
  • Serum creatinine levels more than twice the upper limit of normal range
  • Female patients must be neither lactating nor pregnant as demonstrated by a negative pregnancy test at screening and pre-dose and must be willing to take measures not to become pregnant during the study period and safety follow-up period (abstinence or oral contraceptives or double barrier contraception, such as male condom, female condom or diaphragm)
  • Any prohibited medication

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Plasmodium falciparum
Patients with Plasmodium falciparum malaria
Drug: DSM265 400mg
Drug: DSM265 xmg
Dose of DSM265 to be determined based on the results of the first cohort
Drug: DSM265 ymg
Dose of DSM265 to be determined based on the results of the second cohort
Experimental: Plasmodium vivax
Patients with Plasmodium vivax malaria
Drug: DSM265 400mg
Drug: DSM265 xmg
Dose of DSM265 to be determined based on the results of the first cohort
Drug: DSM265 ymg
Dose of DSM265 to be determined based on the results of the second cohort

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Adequate Clinical and Parasitological Response rate at Day 14
Time Frame: Day 14
Day 14 clinical and parasitological response rate for Plasmodium falciparum and Plasmodium vivax cohorts
Day 14
Pharmacokinetic parameter for exposure up to 168 hours
Time Frame: Day 0 to 168 hours post-dose
Area under the plasma concentration vs time curve from time zero up to and including Day 7 (AUC 0-168)
Day 0 to 168 hours post-dose
Pharmacokinetic parameter for exposure AUC (0-t)
Time Frame: Day 0 to Day 28
Area under the plasma concentration vs time curve from time zero to the time of the last measurable concentration post-dose
Day 0 to Day 28
Area under the plasma concentration vs time curve from time zero to infinity
Time Frame: To Day 28
Area under the plasma concentration vs time curve from time zero to the infinity. Participants will be followed for 28 days, data will be extrapolated.
To Day 28
Maximum plasma concentration (Cmax)
Time Frame: Day 0 to Day 28
Pharmacokinetic parameter maximum plasma concentration
Day 0 to Day 28
Time to reach maximum plasma concentration (tmax)
Time Frame: Day 0 to Day 28
Pharmacokinetic parameter: Time to reach maximum plasma concentration (tmax)
Day 0 to Day 28
Terminal half-life (t½)
Time Frame: Day 0 to Day 28
Pharmacokinetic parameter: Terminal half-life
Day 0 to Day 28
The plasma concentration at 168hours post-dose (C168h)
Time Frame: Day 7
Pharmacokinetic parameter C168 hours
Day 7
The terminal elimination rate constant
Time Frame: Day 0 to 28
Pharmacokinetic parameter: The terminal elimination rate constant (Lambda z)
Day 0 to 28

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Parasite Clearance kinetics
Time Frame: Day 0 to 28
  1. Parasite clearance time
  2. PRR (Parasite reduction rate) and parasitemia half life

  3. Times to microscopic clearance of asexual parasites

    1. Total reduction
    2. 99% reduction
    3. 90% reduction
    4. 50% reduction
  4. Percent reduction in asexual parasites from baseline (microscopically measured) at 24, 48 and 72 hours post-dose
  5. Proportion of aparasitemic patients at 24, 48 and 72 hours post-dose
Day 0 to 28
Endpoints concerning Safety and tolerability of DSM265 in patients
Time Frame: Day 0 to 28

For P. falciparum and for P. vivax:

  1. Incidence, severity, drug-relatedness, seriousness of adverse events
  2. Laboratory values (biochemistry and haematology)
  3. Vital signs
  4. ECG findings, including heart rate, ECG intervals (PR, QTcB, QTcF), conduction changes or abnormalities
Day 0 to 28
Endpoints concerning gametocytemia
Time Frame: Days 0 to 28

  1. Percent microscopic reduction in gametocytes (stratified by gametocyte status at inclusion) from baseline at

    1. 24 hours after administration of study drug
    2. 72 hours after administration of study drug
  2. Proportion of subjects with gametocytes (stratified by gametocyte status at inclusion)
  3. Area under the curve (AUC) over 14 and 28 days for gametocyte density (stratified by gametocyte status at inclusion)
Days 0 to 28
The effect of DSM265 on signs and symptoms of malaria
Time Frame: Day 0 to Day 28
  1. 28 day Adequate Clinical and Parasitological Response (for P. vivax and P. falciparum)
  2. Kaplan Meier survival analysis for rate of recurrence, recrudescence and new infection over 28 days in comparison to historical controls
Day 0 to Day 28
Antimalarial pharmacodynamics - minimum parasiticidal concentration, Minimum Inhibitory Concentration, Time and concentration of parasitemia nadir
Time Frame: Day 0 to Day 28
  1. Minimum Parasiticidal Concentration
  2. Minimum Inhibitory Concentration
  3. Time and concentration of parasitemia nadir (if observed)
  4. A model based link between observed pharmacokinetics and observed parasite density over time
Day 0 to Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medicines for Malaria Venture

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Asociacion Civil Selva Amazonica

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Alejandro Llanos, Professor, Clínica de la Asociación Civil Selva Amazónica

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 15, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 23, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 25, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 22, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 21, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MMV_DSM265_13_02

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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