DSM265 Phase IIa Investigation Treating Plasmodium Falciparum or Vivax

NCT ID: NCT02123290

Last Updated: 2016-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2016-01-31

Brief 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. 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).

Conditions

Plasmodium Falciparum Malaria; Plasmodium Vivax Malaria

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Plasmodium falciparum

Patients with Plasmodium falciparum malaria

Group Type: EXPERIMENTAL

DSM265 400mg

Intervention Type: DRUG

DSM265 xmg

Intervention Type: DRUG

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

DSM265 ymg

Intervention Type: DRUG

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

Plasmodium vivax

Patients with Plasmodium vivax malaria

Group Type: EXPERIMENTAL

DSM265 400mg

Intervention Type: DRUG

DSM265 xmg

Intervention Type: DRUG

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

DSM265 ymg

Intervention Type: DRUG

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

Interventions

DSM265 400mg

Intervention Type: DRUG

DSM265 xmg

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

Intervention Type: DRUG

DSM265 ymg

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Asociacion Civil Selva Amazonica

OTHER

Sponsor Role: collaborator

Medicines for Malaria Venture

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alejandro Llanos, Professor

Role: PRINCIPAL_INVESTIGATOR

Clínica de la Asociación Civil Selva Amazónica

Locations

Clínica de la Asociación Civil Selva Amazónica

Iquitos, Departamento de Loreto (Amazonía Peruana), Peru

Countries

Peru

References

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.

Reference Type: DERIVED

PMID: 29909069 (View on PubMed)

Other Identifiers

MMV_DSM265_13_02

Identifier Type: -

Identifier Source: org_study_id