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

Phase 1

• Conditions: Healthy volunteers; controlled human malaria infection with PfSPZ; MedDRA version: 18.1Level: PTClassification code 10025494Term: Malaria prophylaxisSystem Organ Class: 10042613 - Surgical and medical procedures; Therapeutic area: Diseases [C] - Parasitic Diseases [C03]

• Registration Number: EUCTR2014-005510-34-DE
• Lead Sponsor: Medicines for Malaria Venture

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-03-19
• Last Update Posted: 17 July 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1.Age = 18 and = 45 years healthy volunteers (males or females)
2.Good health based on medical history and on a physical examination without clinically significant findings
3.A body mass index (BMI) >18 and < 30 kg/m2
4.Laboratory results without clinically significant findings within 28 days prior to enrolment
5.Negative urine drug screening test at screening visit (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates)
6.For female subjects, negative beta-HCG pregnancy test (urine or serum) at screening visit and on the day before first dose of DSM265 and PfSPZ Challenge injection
7.Sexually active male volunteers must agree to use a medically acceptable form of contraception from the day of enrolment in the study and continue it for 120 days after the last dose of study medication
8.Women may only be included if they are either
- Identified as women of non-child bearing potential (WNCBP): surgically sterile (by hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy) as documented by an operative report or by ultrasound or postmenopausal ( without use of oral contraceptive for >12 months and either spontaneous amenorrhea for = 12 months or spontaneous amenorrhea for 6-12months and FSH = 40 IU/mL)
or
- Identified as women of child bearing potential (WCBP) and willing and able to practice one of the below listed continuous acceptable methods of contraception (i.e. contraception method used must be one that results in a low failure rate; i.e. 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 prior to the first dose of the study drug + condoms
from the day of screening up to at least 60 days after the last dose of DSM265
9.Agreement to allow the investigators to discuss the volunteer's medical history with their General Practitioner and to sign a request to release medical information concerning contra-indications for participation in the study
10.Able and willing (in the Investigator's opinion) to comply with all study requirements for the duration of the study.
11.Agreement to undergo all study procedures, to attend all study visits and stay overnight for observation if required, up to last follow-up visit
12.Willingness to undergo a CHMI by DVI with PfSPZ Challenge
13.Able and willing to answer all questions on the informed consent quiz correctly demonstrating an understanding of the meaning and of the procedures associated to the study
14.Able and willing to sign the informed consent form for study protocol
15.Reachable (24/7) by mobile phone or electronic mail during the whole study period
16.Agreement to refrain from blood donation during the course of the study and after the end of their involvement in the study according to the local and national blood banking eligibility criteria
17.Willingness to take a curative regimen of artemether-lumefantrine (Riamet®) or another registered antimalarial if necessary

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1Any history of malaria
2.Plans to travel to malaria endemic region during the study period up to last follow-up visit
3.Plans to travel outside of Germany during the challenge period
4.Volunteers unable to be closely followed for social, geographic or psychological reasons
5.Previous participation in any malaria vaccine study vaccine or CHMI study
6.Participation in any other clinical study within 30 days prior to enrolment in the study, or plan to participate in another investigational vaccine/drug research during the study period.
7.Woman who is breast-feeding or planning to become pregnant during the time interval needed to complete the study.
8.Positive HIV, HBV (Seropositive for hepatitis B surface antigen (HBsAg)) or HCV tests
9.Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection, asplenia, recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months before enrolment (inhaled and topical steroids are allowed)
10.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 five years prior to enrolment, history of a suicide plan or attempt.
11.A history of convulsions or of severe head trauma in volunteer
12.Symptoms, physical signs and laboratory 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 the health of the volunteers
13.History of cancer (except basal cell carcinoma of the skin)
14.History of diabetes mellitus
15.History of arrhythmias or documented prolonged QTF-interval (>450msec)
16.Clinically significant abnormalities in electrocardiogram (ECG) 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)
17.Falling 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
18.Positive family history in 1st and 2nd degree relatives <50 years for cardiac disease
19.A history of psoriasis or porphyria, which may be exacerbated after treatment with chloroquine
20.A history of splenectomy
21.Sickle cell anaemia or other red blood cell disorders
22.A history of allergy or contra-indications to or having contraindications to the use of chloroquine phosphate, atovaquone-proguanil (cohort 1B only), artemether or lumefantrine
23.Use of any prescription drugs (except contraception), herbal supplements (Saint-John’s Wort), or over-the-counter (OTC) medication within 2 weeks prior to initial dosing or 5x half-lives, whichever is longer. [If necessary paracetamol, vitamins and topical treatments are acceptable after approval by the study Sponsor; these treatments will be documented in the case report form (CRF).]
24.Use or anticipated use of medications known to cause drug reactions with rescue medications or atovaquone-proguanil (Malarone) such as cimetidine, metoclopramide, antacids and taken at any point during the study period (Note: During the study, the use of metoclopramide as a rescue me

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified