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DSM265 Prophylaxis of Plasmodium Falciparum Malaria

Phase 1
Completed
Conditions
Healthy
Interventions
Drug: Placebo
Biological: Sporozoites
Biological: Infective mosquito bite
Registration Number
NCT02562872
Lead Sponsor
Medicines for Malaria Venture
Brief Summary

The study is a single centre, randomised, placebo-controlled, double-blind study with DSM265 including up to two cohorts of healthy male and female volunteers aged 18 to 45 years.

The study will be conducted into two sequential parts (Cohort 1 and Cohorts 2a and 2b).

Detailed Description

Cohort 1:

* Controlled human malaria infection on Day 0 (Direct Venous Inoculation of 3200 cryopreserved Plasmodium falciparum sporozoites)

* Drug administration on Day -3

* 8 subjects: 6 DSM265 400 mg: 2 matching placebo Clinical safety review of Cohort 1 in order to proceed to Cohorts 2a and 2b

Cohort 2a:

* Controlled human malaria infection on Day 0 (Direct Venous Inoculation of 3200 cryopreserved Plasmodium falciparum sporozoites)

* Drug administration on Day -X (to be defined following safety and pharmacokinetic data)

* 8 subjects: 6 DSM265 400 mg: 2 matching placebo

Cohort 2b:

* Controlled human malaria infection on Day 0 (infected mosquito bite)

* Drug administration on Day -X (to be defined following safety and pharmacokinetic data)

* 8 subjects: 6 DSM265 400 mg: 2 matching placebo

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
Inclusion Criteria

Not provided

Exclusion Criteria
  • Any history of malaria; any severe reactions to mosquito or insect bites; any history of anaphylaxis
  • Plans to travel to malaria endemic region during the study period
  • Previous participation in any malaria vaccine study or controlled human malaria infection study
  • Participation in any other clinical study within 30 days of enrollment or plan to participate in another investigational vaccine/drug research during the study
  • Breastfeeding or planning to become pregnant during the time of the study
  • Positive Human Immunodeficiency Virus, Hepatitis B or C tests
  • Any confirmed/suspected immunosuppressive or immunodeficient state
  • History of serious psychiatric condition that may affect participation in the study, or history of convulsions, seizures, or of severe head trauma
  • Symptoms, physical signs or laboratory values suggestive of systemic disorders
  • History of cancer (except basal cell carcinoma of the skin)
  • History of arrhythmias or documented prolonged QTcF-interval (>450 msec) or 12-lead ECG demonstrating specific abnormalities
  • Moderate risk or higher for cardiovascular event within 5 years (>10%)
  • Positive family history in 1st or 2nd degree relative <50 years for cardiac disease, or history of, or known active cardiac disease
  • history of: psoriasis or porphyria which may be exacerbated by chloroquine; splenectomy, or sickle cell anaemia or other red blood cell disorders; allergy or contra-indication to chloroquine or atovaquone-proguanil
  • Treatment with an investigational drug within 28 days or 5 half-lives of study medication; use of any drugs or dietary supplements within 7 days or 5 half-lives prior to study medication. Herbal supplements must be discontinued at least 28 days prior to study medication. As an exception, acetaminophen or ibuprofen may be used as approved by the investigator
  • Use of any prohibited medication
  • Grapefruit or product containing grapefruit from28 days before study medication or throughout the study
  • History of drug or alcohol abuse within 12 months prior to dosing, or laboratory evidence of abuse
  • Current smoking of more than 10 cigarettes or equivalent per day
  • Plan for major surgery between enrolment and study completion

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort 2b PlaceboPlacebo-
Cohort 1 Active DSM265DSM265-
Cohort 1 PlaceboSporozoites-
Cohort 2a Active DSM265Sporozoites-
Cohort 2a PlaceboPlacebo-
Cohort 2a PlaceboSporozoites-
Cohort 2b Active DSM265Infective mosquito bite-
Cohort 1 Active DSM265Sporozoites-
Cohort 1 PlaceboPlacebo-
Cohort 2b PlaceboInfective mosquito bite-
Cohort 2a Active DSM265DSM265-
Cohort 2b Active DSM265DSM265-
Primary Outcome Measures
NameTimeMethod
Number of subjects with positive parasitemia28 days

positive parasitemia detected by qRT-PCR

Time interval between challenge and the first positive parasitemia28 days

Time from infection to peripheral parasitemia (qRT-PCR) in DSM265 / placebo treated subjects in each cohort given as a geometric mean \[days\]

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Fred Hutchinson Cancer Research Center - Prevention Center

🇺🇸

Seattle, Washington, United States

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