Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201211000433272 Date of Registration: 10/10/2012
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Malaria Challenge Study
Official scientific title A pilot study to optimise controlled human malaria infections in humans with varying degrees of prior exposure to malaria using P. falciparum sporozoites administered by needle and syringe
Brief summary describing the background and objectives of the trial Controlled human malaria infection (CHMI) trials are carried out in a controlled environment, they allow unprecedented detailed evaluation of parasite growth and immunological responses, providing essential information for vaccine and drug development. This is a CHMI study of 28 healthy adults with varying degrees of prior exposure to malaria in Kenya. Assessing parasite growth dynamics post CHMI and examining the relationship between this and lab assays of functional immunity to P.falciparum
Type of trial CCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Prevention
Anticipated trial start date 06/05/2013
Actual trial start date 06/05/2013
Anticipated date of last follow up 08/08/2013
Actual Last follow-up date 13/03/2013
Anticipated target sample size (number of participants) 28
Actual target sample size (number of participants) 28
Recruitment status Completed
Publication URL http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0065960#s2
Secondary Ids Issuing authority/Trial register
SSC 2313 KEMRI Scientific Steering Committee
OxTREC Reference 161-12 Oxford Tropical Research Ethics Committee
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Non-randomised Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group P.falciparum sporozoites (Pf SPZ) Challenge 25,000 Sporozoites Stat dose Aseptic, purified, cryopreserved P. falciparum sporozoites (PfSPZ) for challenge (PfSPZ Challenge), two injections of 50µl containing 12,500 sporozoites in in two deltoid sites, administered to individuals with minimal prior exposure to malaria 2 Dose Comparison
Experimental Group P.falciparum sporozoites (Pf SPZ) Challenge 25,000 Sporozoites Stat dose Aseptic, purified, cryopreserved P. falciparum sporozoites (PfSPZ) for challenge (PfSPZ Challenge), two injections of 50µl containing 12,500 sporozoites in in two deltoid sites, administered to individuals with maximal prior exposure to malaria 2 Dose Comparison
Experimental Group P.falciparum sporozoites (Pf SPZ) Challenge 125,000 Sporozoites Stat dose Aseptic, purified, cryopreserved P. falciparum sporozoites (PfSPZ) for challenge (PfSPZ Challenge), two injections of 50µl containing 62,500 sporozoites in in two deltoid sites, administered to individuals with minimal prior exposure to malaria 10 Dose Comparison
Experimental Group P.falciparum sporozoites (Pf SPZ) Challenge 125,000 Sporozoites Stat dose Aseptic, purified, cryopreserved P. falciparum sporozoites (PfSPZ) for challenge (PfSPZ Challenge), receiving 125,000 sporozoites administered intramuscularly in 2 sites (one injection of 50µl containing 62,500 sporozoites in each deltoid), administered to individuals with maximal prior exposure to malaria 10 Dose Comparison
Experimental Group P.falciparum sporozoites (Pf SPZ) Challenge 75,000 Sporozoites Stat dose Aseptic, purified, cryopreserved P. falciparum sporozoites (PfSPZ) for challenge (PfSPZ Challenge), two injections of 50µl containing 37,500 sporozoites in two deltoid sites, administered to individuals with maximal prior exposure to malaria 2
Experimental Group P.falciparum sporozoites (Pf SPZ) Challenge 75,000 Sporozoites Stat dose Aseptic, purified, cryopreserved P. falciparum sporozoites (PfSPZ) for challenge (PfSPZ Challenge), two injections of 50µl containing 37,500 sporozoites in two deltoid sites, administered to individuals with minimal prior exposure to malaria 2 Dose Comparison
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Healthy adults aged 18 to 40 years. Minimum of 4 completed years (Form 4) of secondary education. Able and willing (in the Investigator¿s opinion) to comply with all study requirements. Informed consent to undergo CHMI. Answer all questions on the informed consent questionnaire correctly. Willingness to take a course of curative anti-malaria medication. Agreement to stay in an in-patient unit during a part of the study (from day of administration of PfSPZ Challenge until completion of curative course of atovaquone/ proguanil hydrochloride given either at malaria diagnosis or day 21 post administration of PfSPZ Challenge). Use of effective method of contraception for duration of study (women only). ¿ PCR positive for P. falciparum parasites at screening. ¿ Use of systemic antibiotics with known antimalarial activity within 30 days of administration of PfSPZ Challenge (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin). ¿ Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period. ¿ Current participation in another clinical trial or recent participation within 12 weeks of enrolment. ¿ Prior receipt of an investigational malaria vaccine. ¿ 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 (inhaled and topical steroids are allowed). ¿ Use of immunoglobulins or blood products within 3 months prior to enrolment. ¿ Haemoglobinopathy (sickle-cell trait) deemed to interfere with study endpoints ¿ A history of allergic disease or reactions likely to be exacerbated by malaria infection. ¿ Contraindications to atovaquone/proguanil hydrochloride. ¿ History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). ¿ History of serious psychiatric condition that may affect participation in the study. ¿ Any other serious chronic illness requiring hospital specialist supervision. ¿ Women only; pregnancy, intention to become pregnant or breast-feeding during study. ¿ Suspected or known current alcohol abuse. ¿ Suspected or known injecting drug abuse. ¿ Seropositive for hepatitis B surface antigen (HBsAg). ¿ Seropositive for hepatitis C virus (antibodies to HCV) with PCR positive for Hepatitis C. ¿ Positive family history in 1st and 2nd degree relatives < 50 years old for cardiac disease. ¿ Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination. ¿ Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data. Exclusion Criterion on Day of Challenge ¿ Acute disease, defined as moderate or severe illness with or without fever (temperature >37.5oC. 18 Year(s) 40 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 13/08/2012 Oxford Tropical Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
University of Oxford Joint Research Office, Block 60 Churchill Hospital Oxford OX3 7LE United Kingdom
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 30/10/2012 KEMRI Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
KEMRI, Mbagathi Road Nairobi 54840-00200 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The infectivity of PfSPZ Challenge in healthy Kenyan adults will be assessed using thick film microscopy and highly sensitive PCR for P. falciparum DNA. Day 6.5 to day 21 post enrollment
Secondary Outcome Volunteers' natural immunity to P. falciparum will be assessed by comparing parasite growth dynamics between volunteers with maximum and minimal prior exposure to malaria following CHMI. Day -1 to day 90 post enrollment
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
KEMRI CCR KEMRI Centre for Clinical Research, Mbagathi Road Nairobi 54840-00200 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
EDCTP Francie van Zijl Drive, Parowvallei Cape Town 7505 South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Secondary Sponsor Sanaria Inc 9800 Medical Center Drive, Suite A209 Rockville MD 20850 United States of America Commercial Sector/Industry
Primary Sponsor Univeristy of Oxford Joint Research Office Block 60, Churchill Hospital, Old Road, Headington Oxford OX3 7LE United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
KEMRI Wellcome Trust Research Programme Bofa Road, Off Hospital Grounds Kilifi 230-80108 Kenya
Sanaria Inc 9800 Medical Center Drive, Suite A209 Rockville, Maryland 20850 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Kevin Marsh kmarsh@kemri-wellcome.org +254(0)417522063 Bofa Road, Off Hospital Grounds
City Postal code Country Position/Affiliation
Kilifi 230-80108 Kenya Prinicpal Investigator
Role Name Email Phone Street address
Principal Investigator Bernhards Ogutu bernhards.ogutu@indepth-network.org +254(0)202722541 KEMRI Centre for Clinical Research, Mbagathi Road
City Postal code Country Position/Affiliation
Nairobi 54840-00200 Kenya Prinicpal Investigator
Role Name Email Phone Street address
Public Enquiries Elizabeth Juma jumaelizabeth@yahoo.com +254(0)202722541 KEMRI Centre for Clinical Research, Mbagathi Road
City Postal code Country Position/Affiliation
Nairobi 54840-00200 Kenya Investigator
Role Name Email Phone Street address
Scientific Enquiries Susanne Sheehy susanne.sheehy@balliol.ox.ac.uk +447811207338 Univeristy of Oxford, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Old Road Campus
City Postal code Country Position/Affiliation
Oxford OX3 7LJ United Kingdom Investigator
REPORTING
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