DSM265 Prophylaxis of Plasmodium Falciparum Malaria

Proof-of-concept, Single Center Study in Healthy Adult Volunteers to Investigate Safety, Tolerability, Pharmacokinetics and Prophylactic Activity of Single Dose DSM265 in a Controlled Human Malarial Infection Challenge Either by Direct Venous Inoculation of Plasmodium Falciparum Sporozoites or Mosquito-borne Plasmodium Falciparum

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).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: DSM265; Biological: Sporozoites; Drug: Placebo; Biological: Infective mosquito bite

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

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center - Prevention Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

• Good health based on medical history and physical examination
• body mass index >18 and <30kg/m2
• Laboratory results without clinically significant findings within 60 days
• Males must use medically acceptable form of contraception from the dose of DSM265/Placebo for 120 days
• Women must be of non-child bearing potential or willing and able to practice one of the required continuous acceptable methods of contraception and have negative pregnancy tests
• Able & willing to comply with all study requirements throughout the study
• Agree to undergo all study procedures, attend all study visits and stay overnight for observation if required, to last follow-up visit
• Willing to undergo a controlled human malaria infection by mosquito bites / inoculation
• Able and willing to answer all questions on informed consent correctly, and to sign the informed consent form
• Reachable constantly by mobile phone or email throughout the study period
• Refrain from blood donation throughout the study
• Willing to take atovaquone-proguanil, Chloroquine or other registered antimalarial

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1 Active DSM265	Drug: DSM265; DSM265 400 mg single oral dose; Biological: Sporozoites; Direct venous inoculation of 3200 cryopreserved Plasmodium falciparum (NF54 strain) sporozoites; Other Names: PfSPZ
PLACEBO_COMPARATOR: Cohort 1 Placebo	Biological: Sporozoites; Direct venous inoculation of 3200 cryopreserved Plasmodium falciparum (NF54 strain) sporozoites; Other Names: PfSPZ; Drug: Placebo; Placebo to match DSM265, single oral dose
EXPERIMENTAL: Cohort 2a Active DSM265	Drug: DSM265; DSM265 400 mg single oral dose; Biological: Sporozoites; Direct venous inoculation of 3200 cryopreserved Plasmodium falciparum (NF54 strain) sporozoites; Other Names: PfSPZ
PLACEBO_COMPARATOR: Cohort 2a Placebo	Biological: Sporozoites; Direct venous inoculation of 3200 cryopreserved Plasmodium falciparum (NF54 strain) sporozoites; Other Names: PfSPZ; Drug: Placebo; Placebo to match DSM265, single oral dose
EXPERIMENTAL: Cohort 2b Active DSM265	Drug: DSM265; DSM265 400 mg single oral dose; Biological: Infective mosquito bite; Five single bites by laboratory reared female Anopheles stephensi mosquitoes carrying Plasmodium falciparum
PLACEBO_COMPARATOR: Cohort 2b Placebo	Drug: Placebo; Placebo to match DSM265, single oral dose; Biological: Infective mosquito bite; Five single bites by laboratory reared female Anopheles stephensi mosquitoes carrying Plasmodium falciparum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with positive parasitemia	positive parasitemia detected by qRT-PCR	28 days
Time interval between challenge and the first positive parasitemia	Time from infection to peripheral parasitemia (qRT-PCR) in DSM265 / placebo treated subjects in each cohort given as a geometric mean [days]	28 days

Collaborators and Investigators

• Sponsor: Medicines for Malaria Venture
• Collaborators: United States Department of Defense; Fred Hutchinson Cancer Center; Center for Infectious Disease Research
• Investigators: Principal Investigator: James G Kublin, MD/MPH, Fred Hutchinson Cancer Research Centre

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2016
• Primary Completion (ACTUAL): May 1, 2017
• Study Completion (ACTUAL): May 1, 2017

Study Registration Dates

• First Submitted: September 28, 2015
• First Submitted That Met QC Criteria: September 28, 2015
• First Posted (ESTIMATE): September 29, 2015

Study Record Updates

• Last Update Posted (ACTUAL): January 14, 2022
• Last Update Submitted That Met QC Criteria: January 13, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Infection; Malaria; Healthy; Human; Volunteer; Controlled
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria
• Other Study ID Numbers: MMV_DSM265_14_03; CDMRP-PR130402 (OTHER_GRANT: US Department of Defense)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO