DSM265 Chemoprophylaxis of Plasmodium Falciparum Malaria
Evaluation of the Prophylactic Antimalarial Activity of a Single Dose of DSM265 in Non-immune Healthy Adult Volunteers by Controlled Human Malaria Infection With PfSPZ Challenge
1 other identifier
interventional
22
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Oct 2015
Shorter than P25 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 16, 2015
CompletedFirst Posted
Study publicly available on registry
May 21, 2015
CompletedStudy Start
First participant enrolled
October 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2016
CompletedResults Posted
Study results publicly available
December 3, 2020
CompletedJanuary 13, 2021
January 1, 2021
6 months
March 16, 2015
July 22, 2019
January 7, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Infection Rate
The infection rate is the number (percentage) of subjects in a cohort who became positive for parasitemia. Complete protection = Subjects with pre-patent period equal to 28 days.
Day 0 to Day 28 post-inoculum (daily)
Pre-patent Period
The pre-patent period is defined as the time (days) from inoculation with PfSPZ to first occurrence of a positive TBS. If no positive TBS is seen by Day 28, this variable is set to 28 days. Complete protection = Subjects showing with pre-patent period equal to 28 days.
Day 0 to Day 28 post-inoculum (daily)
Secondary Outcomes (14)
Number of Participants With Adverse Events as a Measure of Safety & Tolerability of DSM265
From first dose (Day -1 in Cohort 1A and Day -7 in Cohort 2) to Day 60 post-inoculum
Number of Participants With Treatment Emergent Adverse Events (TEAE) as a Measure of Safety & Tolerability of Malarone
From first dose (Day -1, Cohort 1b) to Day 60 post-inoculum
Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Plasmodium Falciparum Sporozoite Challenge Inoculum
Day 0 to Day 60 post-inoculum
DSM265 Pharmacokinetics Profile - T Max
From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum
DSM265 Pharmacokinetics Profile - T 1/2
From pre-dose of DSM265 (Day -1 in Cohort 1a and Day -7 in Cohort 2) to Day 28 post-inoculum
- +9 more secondary outcomes
Study Arms (4)
Cohort 1a: DSM265/placebo, sporozoite inoculum
EXPERIMENTALDSM265 400mg / placebo Day -1, sporozoite inoculum Day 0
Cohort 1b: Malarone, sporozoite inoculum
ACTIVE COMPARATORMalarone daily for 9 days from Day -1 to Day 7, sporozoite inoculum Day 0
Cohort 2: DSM265/placebo, sporozoite inoculum
EXPERIMENTALDSM265 400mg / placebo Day -7, sporozoite inoculum Day 0
Cohort 3: DSM265 / placebo, sporozoite inoculum (Optional)
EXPERIMENTALDSM265 400mg / placebo Day -X, sporozoite inoculum Day 0
Interventions
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
Eligibility Criteria
You may qualify if:
- 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
- +3 more criteria
You may not qualify if:
- 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
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Universitätsklinikum Tübingen, Institut für Tropenmedizin
Tübingen, 72074, Germany
Related Publications (1)
Sulyok M, Ruckle T, Roth A, Murbeth RE, Chalon S, Kerr N, Samec SS, Gobeau N, Calle CL, Ibanez J, Sulyok Z, Held J, Gebru T, Granados P, Bruckner S, Nguetse C, Mengue J, Lalremruata A, Sim BKL, Hoffman SL, Mohrle JJ, Kremsner PG, Mordmuller B. DSM265 for Plasmodium falciparum chemoprophylaxis: a randomised, double blinded, phase 1 trial with controlled human malaria infection. Lancet Infect Dis. 2017 Jun;17(6):636-644. doi: 10.1016/S1473-3099(17)30139-1. Epub 2017 Mar 28.
PMID: 28363637RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Jörg Möhrle
- Organization
- Medicines for Malaria Venture
Study Officials
- PRINCIPAL INVESTIGATOR
Benjamin Mordmüller, Dr. med
Institut für Tropenmedizin, Uni. of Tübingen
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 16, 2015
First Posted
May 21, 2015
Study Start
October 1, 2015
Primary Completion
April 1, 2016
Study Completion
April 1, 2016
Last Updated
January 13, 2021
Results First Posted
December 3, 2020
Record last verified: 2021-01
Data Sharing
- IPD Sharing
- Will not share