DSM265 Chemoprophylaxis of Plasmodium Falciparum Malaria
Condition: Plasmodium Falciparum, Malaria
MeSH terms: Malaria
Intervention: DSM265 400mg; Placebo to DSM265 400 mg; Plasmodium falciparum sporozoite challenge; Malarone
Intervention description: DSM265 400mg, single oral administration in a fed state; Placebo to DSM265 400mg, single oral administration in a fed state; IV Plasmodium falciparum sporozoites (3200) by direct venous inoculation; 250 mg atovaquone, 100 mg proguanil hydrochloride
Intervention MeSH terms: Atovaquone; Proguanil; Atovaquone, proguanil drug combination
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Malaria, Plasmodium falciparum sporozoite challenge, DSM265

Summary:

      Study to evaluate the efficacy of DSM265 as a causal prophylactic in a standardized and
      validated Human Challenge model using direct venous inoculation of aseptic, purified,
      cryopreserved, vialed Plasmodium falciparum sporozoites.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Good health based on medical history and physical examination- Body mass index >18 and
             <30 kg/m2

          -  Lab results without clinically significant findings in 28 days prior to enrolment

          -  Negative drug screening test

          -  Females: negative pregnancy test at screening and on the day before first dose of
             DSM265 and sporozoite challenge injection

          -  Sexually active males must agree to use a medically acceptable form of contraception
             from enrolment and continue for 12 weeks after the dose of DSM265

          -  Women may only be included if they are either Identified as not of child bearing
             potential, or if of child bearing potential and willing and able to practice one of
             the continuous acceptable methods of contraception (must be one with failure rate less
             than 1% per year) with double barrier protection:

               -  Intrauterine device+condoms,

               -  Diaphragms+spermicidal gel/foam+condoms,

               -  Hormonal contraceptives (oral, depot, patch, injectable or vaginal ring)
                  stabilized for at least 30 days before the study drug + condoms from screening to
                  at least 60 days after dose of DSM265

          -  Agree to allow the investigators to discuss the medical history with General
             Practitioner and to sign a request to release medical information concerning
             contra-indications for participation in the study

          -  Able and willing to comply with all study requirements for the duration of the study

          -  Agree to undergo all study procedures, to attend all study visits and stay overnight
             for observation if required, up to last follow up visit

          -  Willing to undergo a sporozoite challenge

          -  Able and willing to answer all questions on the informed consent quiz correctly
             demonstrating an understanding of the meaning and of the study procedures

          -  Able and willing to sign the informed consent form

          -  Reachable (24/7) by mobile phone or email during the whole study period

          -  Agree to refrain from blood donation during the course of the study and after the end
             of involvement in the study according to the local and national blood banking
             eligibility criteria (currently 4 years in Germany)

          -  Willing to take a curative regimen of Riamet or another registered antimalarial if
             necessary

        Exclusion Criteria:

          -  Any history of malaria

          -  Plans to travel to malaria endemic region during the study period up to last follow up
             visit or plans to travel outside of Germany during the challenge period

          -  unable to be closely followed for social, geographic or psychological reasons

          -  Previous participation in any malaria vaccine study or controlled human malaria
             infection study

          -  Participation in any other clinical study within 30 days before enrolment in the
             study, or plan to participate in another investigational vaccine/drug research during
             the study period.

          -  Woman who is breast-feeding or planning to become pregnant during the study

          -  Positive human immunodeficiency virus, seropositive for hepatitis B surface antigen or
             Hepatitis C virus tests

          -  Any confirmed/suspected immunosuppressive or immunodeficient state, including human
             immunodeficiency virus infection, asplenia, recurrent, severe infections and chronic
             (more than 14 days) immunosuppressant medication within the 6 months before enrolment
             (inhaled and topical steroids are allowed)

          -  History of serious psychiatric condition that may affect participation in the study,
             precludes compliance with the protocol; past or present psychoses; disorder requiring
             lithium; or within 5 years prior to enrolment, history of a suicide plan or attempt.

          -  History of convulsions or severe head trauma

          -  Symptoms, physical signs and lab values suggestive of systemic disorders including
             renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, and other
             conditions which could interfere with the interpretation of the study results or
             compromise health

          -  History of cancer (except basal cell carcinoma of the skin), or diabetes mellitus or
             of arrhythmias or documented prolonged QTF-interval (>450msec)

          -  Clinically significant abnormalities in electrocardiogram at screening: pathologic Q
             wave, prolonged QT interval, and significant ST-T wave changes, left ventricular
             hypertrophy, non-sinus rhythm except isolated premature atrial contractions, right or
             left bundle branch block, advanced A-V heart block (type 2 or type 3)

          -  In moderate risk or higher categories for fatal or non-fatal cardiovascular event
             within 5 years (>10%) determined by non-invasive criteria for cardiac risk

          -  Positive family history in relatives <50 years for cardiac disease

          -  History of psoriasis or porphyria, which may be exacerbated by chloroquine

          -  History of splenectomy

          -  Sickle cell anaemia or other red blood cell disorders

          -  History of allergy or contra-indications to or having contraindications to the use of
             chloroquine phosphate, atovaquone-proguanil (cohort 1B), artemether or lumefantrine

          -  Use of any prescription drugs (except contraception), herbal supplements or
             over-the-counter medication in 4 weeks before dosing or 5x half-lives, whichever is
             longer

          -  Use or anticipated use of medications known to cause drug reactions with rescue
             medications or Malarone, such as cimetidine, metoclopramide, antacids and taken at any
             point during the study period.

          -  Intake of grapefruit, grapefruit juice, Seville orange or other products containing
             these ingredients within 7 days of the first drug administration

          -  Use of chronic immunosuppressive drugs, or other immune modifying drugs within 6
             months of enrolment (inhaled and topical corticosteroids and oral anti-histaminic are
             allowed) and/or during the study period

          -  Use of systemic antibiotics with known antimalarial activity within 30 days of study
             enrolment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin,
             erythromycin, fluoroquinolones, or azithromycin ) and/or during the study period

          -  Use of immunoglobulins or blood products in 3 months prior to enrolment

          -  Suspected/known injecting drug abuse in 5 years preceding enrolment

          -  Current smoking more than 10 cigarettes or equivalent per day

          -  Plan for major surgery between enrolment and follow up