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AzTrials

Plasmodium Falciparum MalariaPhase 2NCT02123290

DSM265 Phase IIa Investigation Treating Plasmodium Falciparum or Vivax

A Phase 2 study testing DSM265 400mg, DSM265 xmg and DSM265 ymg in people with Plasmodium Falciparum Malaria and Plasmodium Vivax Malaria, run by Medicines for Malaria Venture at 1 site in Peru.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 60 years
What is being tested?
DSM265 400mg, DSM265 xmg and DSM265 ymg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
1 sitePeru
Study dates
Jan 2016to Jan 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Body weight between 45kg and 90kg
  • Mono-infection of P. falciparum or P. vivax confirmed by:
  • Fever, or history of fever in the previous 24 hours and,
  • Microscopically confirmed parasite infection: 1,000 to 35,000 asexual parasite count/µL blood
  • Written informed consent
  • Able to swallow oral medication
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

Peru1 site

  • Clínica de la Asociación Civil Selva Amazónica

    Iquitos, Departamento de Loreto (Amazonía Peruana)

Other trials in Peru

About this study

Official title: 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).

Being tested
DSM265 400mg, DSM265 xmg, DSM265 ymg
Keywords
Plasmodium, falciparum, malaria, vivax, DSM265, pharmacokinetics, adult
Medical subject headings
Malaria, Falciparum, Malaria, Vivax, Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DSM265 400mgDrug

  • DSM265 xmgDrug

    Dose of DSM265 to be determined based on the results of the first cohort

  • DSM265 ymgDrug

    Dose of DSM265 to be determined based on the results of the second cohort

Study groups in NCT02123290
Study groupRoleWhat they receive
Plasmodium falciparumExperimentalPatients with Plasmodium falciparum malaria
Receives: Drug: DSM265 400mg; Drug: DSM265 xmg; Drug: DSM265 ymg
Plasmodium vivaxExperimentalPatients with Plasmodium vivax malaria
Receives: Drug: DSM265 400mg; Drug: DSM265 xmg; Drug: DSM265 ymg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adequate Clinical and Parasitological Response rate at Day 14

    Day 14 clinical and parasitological response rate for Plasmodium falciparum and Plasmodium vivax cohorts

    Measured: Day 14

  2. Pharmacokinetic parameter for exposure up to 168 hours

    Area under the plasma concentration vs time curve from time zero up to and including Day 7 (AUC 0-168)

    Measured: Day 0 to 168 hours post-dose

  3. Pharmacokinetic parameter for exposure AUC (0-t)

    Area under the plasma concentration vs time curve from time zero to the time of the last measurable concentration post-dose

    Measured: Day 0 to Day 28

  4. Area under the plasma concentration vs time curve from time zero to infinity

    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.

    Measured: To Day 28

  5. Maximum plasma concentration (Cmax)

    Pharmacokinetic parameter maximum plasma concentration

    Measured: Day 0 to Day 28

  6. Time to reach maximum plasma concentration (tmax)

    Pharmacokinetic parameter: Time to reach maximum plasma concentration (tmax)

    Measured: Day 0 to Day 28

  7. Terminal half-life (t½)

    Pharmacokinetic parameter: Terminal half-life

    Measured: Day 0 to Day 28

  8. The plasma concentration at 168hours post-dose (C168h)

    Pharmacokinetic parameter C168 hours

    Measured: Day 7

  9. The terminal elimination rate constant

    Pharmacokinetic parameter: The terminal elimination rate constant (Lambda z)

    Measured: Day 0 to 28

Secondary outcomes (5)

  1. Parasite Clearance kinetics

    1. Parasite clearance time
    2. PRR (Parasite reduction rate) and parasitemia half life
    3. Times to microscopic clearance of asexual parasites
    4. Total reduction
    5. 99% reduction
    6. 90% reduction
    7. 50% reduction
    8. Percent reduction in asexual parasites from baseline (microscopically measured) at 24, 48 and 72 hours post-dose
    9. Proportion of aparasitemic patients at 24, 48 and 72 hours post-dose

    Measured: Day 0 to 28

  2. Endpoints concerning Safety and tolerability of DSM265 in patients

    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

    Measured: Day 0 to 28

  3. Endpoints concerning gametocytemia

    1. Percent microscopic reduction in gametocytes (stratified by gametocyte status at inclusion) from baseline at
    2. 24 hours after administration of study drug
    3. 72 hours after administration of study drug
    4. Proportion of subjects with gametocytes (stratified by gametocyte status at inclusion)
    5. Area under the curve (AUC) over 14 and 28 days for gametocyte density (stratified by gametocyte status at inclusion)

    Measured: Days 0 to 28

  4. The effect of DSM265 on signs and symptoms of malaria

    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

    Measured: Day 0 to Day 28

  5. Antimalarial pharmacodynamics - minimum parasiticidal concentration, Minimum Inhibitory Concentration, Time and concentration of parasitemia nadir

    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

    Measured: Day 0 to Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2014 (estimated)
  2. Study startJan 2016
  3. Primary completionJan 2016
  4. Study completionJan 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02123290
Sponsor's protocol ID
MMV_DSM265_13_02
Status last verified
Jun 2016
First submitted
15 Apr 2014
Last updated
22 Jun 2016
Results posted
No
Data monitoring committee
Yes

Publications

  • Llanos-Cuentas A, Casapia M, Chuquiyauri R, Hinojosa JC, Kerr N, Rosario M, Toovey S, Arch RH, Phillips MA, Rozenberg FD, Bath J, Ng CL, Cowell AN, Winzeler EA, Fidock DA, Baker M, Mohrle JJ, Hooft van Huijsduijnen R, Gobeau N, Araeipour N, Andenmatten N, Ruckle T, Duparc S. Antimalarial activity of single-dose DSM265, a novel plasmodium dihydroorotate dehydrogenase inhibitor, in patients with uncomplicated Plasmodium falciparum or Plasmodium vivax malaria infection: a proof-of-concept, open-label, phase 2a study. Lancet Infect Dis. 2018 Aug;18(8):874-883. doi: 10.1016/S1473-3099(18)30309-8. Epub 2018 Jun 13.

    PubMed 29909069

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DSM265 400mg, DSM265 xmg and DSM265 ymg in people with Plasmodium Falciparum Malaria and Plasmodium Vivax Malaria, run by Medicines for Malaria Venture at 1 site in Peru.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Peru. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adequate Clinical and Parasitological Response rate at Day 14 (time frame: Day 14). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02123290, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2016.

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