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 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: www.pactr.org
Trial no.: PACTR202010540737215 Date of Approval: 01/10/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Assessing Safety and Tolerability of artemether-lumefantrine+atovaquone-proguanil tri-therapy for malaria treatment in Adults and Adolescents in Gabon
Official scientific title Assessing Safety and Tolerability of artemether-lumefantrine+atovaquone-proguanil tri-therapy for malaria treatment in Adults and Adolescents in Gabon
Brief summary describing the background and objectives of the trial Artemisinin-based combination therapies (ACTs), combining a fast-acting artemisinin derivative with a longer half-life partner drug, are currently the first-line treatment for malaria. Their efficacy has declined in South-East Asia because of the emergence of parasite resistance that has the potential to spread through Africa. Although susceptibility to ACTs remains high among the African Plasmodium falciparum population, previous first line antimalarials have been lost quickly due to the spread of resistant parasites. To mitigate this risk and to have a highly efficacious, safe and well tolerated treatment for uncomplicated malaria at hand in the foreseeable scenario of ACT resistance in Africa, more efficacious antimalarial drug combinations need to be explored urgently for quick deployment in Africa.The most vulnerable and affected population by malaria are African children younger than 5 years. Yet, relatively few published studies specifically described the safety of antimalarial triple-therapies in this age group in Africa. We are aware of one triple-ACT trial currently in progress in Kenyan children (https://clinicaltrials.gov/ct2/show/record/NCT03452475) and another one not yet recruiting (https://clinicaltrials.gov/ct2/show/NCT03923725). Before evaluating the suggested treatment in this very vulnerable population, an age step down approach is sought to mitigate potential risks. The aim of this pilot study is to detect in an early phase potential yet unforeseen tolerability and safety issues of this new triple-ACT (AL+AP) in an adolescent and adult African population prior to an age-step down decision for the main clinical trial in young African children.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) ASAAP study I
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/09/2020
Actual trial start date
Anticipated date of last follow up 31/01/2021
Actual Last follow-up date
Anticipated target sample size (number of participants) 60
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
N 005 2020 CNER SG P National Research Ethics Committee of Gabon
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 Randomised Permuted block randomization Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group artemether lumefantrine and atovaquone proguanil artemether-lumefantrine twice daily + atovaquone-proguanil, once daily 3 consecutive days Artemether-lumefantrine is an approved drug combination, can be found on the WHO list of essential medicines, and it is registered in the country where the trial will take place. Atovaquone-proguanil is an approved drug combination but is not registered in the country where the trial will take place. 40
Control Group artemether lumefantrine and placebo artemether-lumefantrine twice daily placebo once daily over 3 consecutive days Artemether-lumefantrine is an approved drug combination, can be found on the WHO list of essential medicines, and it is registered in the country where the trial will take place. Placebo: P-Dragees rosa Lichtenstein, Artesan Pharma GmbH & Co. KG, approval number (Germany): 6927257.00.00 20 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Adults and adolescents aged 15 years and older • Body weight ≥40kg • Fever (≥37.5°C axillary body temperature) or history of fever in the preceding 24 hours • Uncomplicated P. falciparum monoinfection with equal or more than 1,000 and less than 200,000 asexual P. falciparum parasites per µl of blood. • Signed written informed consent • Ability to comply with study procedures and follow-up schedules • Ability to take oral medication • Reported intake of any antimalarial drug including halofantrine within the previous month • Intake of drugs with some antimalarial activity or that interference with tolerability assessment (including cotrimoxazole/bactrim, tetracyclines, quinolones and fluoroquinolones, and azithromycin) within the previous month • Presence of severe malaria following WHO definition (see Annex 2: WHO definitions for severe malaria) • Known history or evidence of clinically significant medical disorders • Severe malnutrition assessed by BMI • Previous participation in a malaria vaccine study • Screening haemoglobin level <7 g/dL • Known hypersensitivity or contraindications to any AL+AP components • Administration of strong inducers of CYP3A4 such as rifampin, carbamazepine, phenytoin, millepertuis/St. John’s wort (hypericum perforatum) • Known QT prolongation (e.g. hypokalaemia, hypomagnesemia) • Pregnant or lactating women • Participation in other interventional studies 80 and over: 80+ Year,Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 15 Year(s) 120 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 30/06/2020 Comite National d Ethique de la Recherche au Gabon
Ethics Committee Address
Street address City Postal code Country
BP 2217 Libreville 000000 Gabon
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Frequency and severity of adverse events by treatment arm in general and related to the administered study drugs in adolescents and adults aged 15 years and older continuously during the conduct of the study
Secondary Outcome Exploratory efficacy in terms of Adequate Clinical and Parasitological Response (ACPR) of participants treated with artemether-lumefantrine+atovaquone-proguanil and participants treated with artemether-lumefantrine for uncomplicated P. falciparum malaria continuously during the conduct of the study
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Centre de Recherches Medicale de Lambarene BP 242 Lambarene 00000 Gabon
FUNDING SOURCES
Name of source Street address City Postal code Country
European and Developing Countries Clinical Trials Partnership Anna van Saksenlaan 51 HW The Hague 2593 Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Kwame Nkrumah University of Science and Technology UPO, PMB Kumasi 00000 Ghana University
COLLABORATORS
Name Street address City Postal code Country
Bernhard Nocht Institute for Tropical Medicine Bernhard Nocht Strasse 74 Hamburg 20359 Germany
Universite Paris Descartes MERIT UMR 261 4, Avenue de l Observatoire Paris 75006 France
Institut de Recherche pour le Developpement MIVEGEC UMR 44, Boulevard de Dunkerque, CS 90009 Marseille cedex 2 13572 France
Institut des Sciences et Techniques P.O. Box 2779 Bobo Dioulasso 01 00000 Burkina Faso
Universite des Sciences des Techniques et des Technologies de Bamako P.O. Box 1805 Point G Bamako 00000 Mali
Institut de Recherche Clinique du Benin 04 BP 1114 Cotonou 00000 Benin
CONTACT PEOPLE
Role Name Email Phone Street address
Scientific Enquiries Oumou Maiga Ascofare maiga@kccr.de +233322060351 KCCR, UPO, PMB, KNUST
City Postal code Country Position/Affiliation
Kumasi 00000 Ghana KCCR KNUST
Role Name Email Phone Street address
Principal Investigator Ghyslain Mombo Ngoma ghyslain.mombongoma@cermel.org +24166072578 BP 242
City Postal code Country Position/Affiliation
Lambarene 00000 Gabon CERMEL
Role Name Email Phone Street address
Public Enquiries John Amuasi amuasi@kccr.de +233322060351 KCCR, UPO, PMB, KNUST
City Postal code Country Position/Affiliation
Kumasi 00000 Ghana KCCR KNUST
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes In line with the funding conditions, IPD is to be shared. However, this will be de-identified IPD that used to generate the results reported (text, tables, figures and appendices). IPD sharing will begin after publication of primary results and will be available for a period which is aligned with the data sharing agreements approved by the research ethics committees of the counties/sites participating in the trial. The IPD shall be made available via a request and evaluation process to investigators whose proposed research has received IRB approval. All investigators to whom this IPD is made available will be required to be part of the execution of a data use agreement. The below mentioned URL will carry information on how to access the IPD at the end of the study and addresses that contain additional information about the plan to share IPD. This will include the repository in which the IPD will be deposited. The website shall also explain the eligibility criteria and internal review processes for reviewing data requests. Clinical Study Report,Informed Consent Form,Study Protocol From the time of publication and for a period which is aligned with the data sharing agreements approved by the research ethics committees of the counties/sites participating in the trial. This IPD shall be made available via a request and evaluation process to investigators whose proposed research has received IRB approval. All investigators to whom this IPD is made available will be required to be part of the execution of a data use agreement. The data shall be made available through a governed data access process which includes a transparent, accountability and decision-making process: Completion of data request form Evaluation by a data access committee Data sharing Agreement Secure transfer of data
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://asaap-malaria.org/ No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 20/10/2020 Full approval obtained of Comite National d Ethique de la Recherche au Gabon TRUE, Comite National d Ethique de la Recherche au Gabon, BP 2217, Libreville, 000000, Gabon, , 30 Jun 2020, +24107791200, xxx@xxx.xxx, 12242_11569_4737.pdf TRUE, Comite National d Ethique de la Recherche au Gabon, BP 2217, Libreville, 000000, Gabon, , 30 Jun 2020, +24107791200, xxx@xxx.xxx, 12242_11569_4737.pdf