A safety and tolerability study in humans for chemically attenuated malaria parasites

Phase 1

Completed

• Conditions: Malaria; Infection - Studies of infection and infectious agents

• Registration Number: ACTRN12614000228684
• Lead Sponsor: Griffith University

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-03-04
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Completed
• Sex: Male
• Target Recruitment: 9

Inclusion Criteria

1. Volunteers will be males, aged 18-60 years of age who do not live alone for the duration of the study.
2. Volunteers must have a BMI within the range of 18-30.
3. Volunteers must understand the procedures involved and agree to participate in the study by giving fully informed, written consent.
4. Be contactable and available for the duration of their study schedule (maximum of 3 months)
5. Volunteers must be non-smokers and in good health, as assessed during pre-study medical examination and by review of screening results
6. Good peripheral venous access

Exclusion Criteria

1. Has increased cardiovascular disease risk (defined as >10%, 5 yr risk) as determined by the method of Gaziano et al. Risk factors include: sex, age, systolic blood pressure, smoking status, body mass index (BMI, kg/mm2), and reported diabetes status and blood pressure.
2. History of splenectomy
3. History of severe allergic reaction, anaphylaxis or convulsion following any vaccination, infusion or treatment with anti-malarial drugs artemether and/or lumefantrine.
4. Presence of current or suspected chronic diseases such as cardiac or autoimmune disease (HIV or other immunodeficiencies), insulin dependent diabetes, progressive neurological disease, severe malnutrition, acute or progressive hepatic disease, acute or progressive renal disease, psoriasis, rheumatoid arthritis, asthma, epilepsy, obsessive compulsive disorder, skin carcinoma excluding non-spreadable skin cancers such as basal cell and squamous cell carcinoma.
5. Known inherited genetic anomaly (known as cytogenic disorders) eg Down’s syndrome.
6. Individuals wishing to donate blood to the Australian Red Cross Blood Service in the future.
7. The volunteer has a diagnosis of schizophrenia, bi-polar disease, severe depression or other severe (disabling) chronic psychiatric disorder. Participants who are receiving a single anti-depressant drug and are stable for at least 3 months prior to enrollment without decompensating may be allowed to enroll in the study at the investigator’s discretion.
8. Has been hospitalised in the past 5 years prior to enrolment for psychiatric illness, history of suicide attempt or confinement for danger to self or others.
9. Known pre-existing prolongation of the QTc interval. Family history of congenital prolongation of the QTc interval on electrocardiograms or of sudden death or any other clinical conditions known to prolong the QTc interval eg volunteers with a history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease.
10. Recent or current therapy with antibiotic or drug with potential antimalarial activity (tetracycline, azithromycin, clindamycin, hydroxychloroquine etc).
11. Concomitant use of any drug which is metabolized by the cytochrome enzyme CYP2D6 (eg flecainide, metoprolol, imipramine, amitriptyline, clomipramine) OR drugs that are known to prolong the QTc interval e.g. antiarrhythmics of classes IA and III, neuroleptics, antidepressant agents, certain antibiotics (including some agents of the following classes: macrolides, fluoroquinolones, imidazole and triazole antifungal agents), certain nonsedating antihistamines (terfenadine, astemizole), cisapride.
12. Use of corticosteroids, anti-inflammatory drugs, any immunomodulators or anticoagulants. Currently receiving or have previously received immunosuppressive therapy, including systemic steroids including ACTH or inhaled steroids in dosages which are associated with hypothalamic-pituitary axis suppression such as 1mg/kg/day or prednisone or its equivalent or chronic use of inhaled high potency corticosteroids (budesonide 800 microgram per day or fluticasone 750 microgram).
13. Presence of acute infectious disease or fever (e.g. sub-lingual temperature greater than or equal to 38.5oC) within the five days prior to the study product administration.
14. Evidence of acute illness within the 4 weeks before trial prior to screening and enrollment.
15. Significant intercurrent disease of any type, in particular liver,

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary Outcome 1: To characterize the safety and tolerability in humans of P. falciparum 7G8 blood stage parasites attenuated with different doses of Tafuramycin-A.<br>[Active monitoring daily from inoculation (ie Day 0) until Day 28. The final visit on Day 90. Passive monitoring (ie participants contacting and reporting any potential adverse events to study staff outside of scheduled visits) from Day 0-Day 90.]