MAMS4CL comprises a clinical trial with three embedded sub-studies designed to comprehensively evaluate the administered treatments and assess the impact of CL treatment on patients and the healthcare system.
The multi-centre multi-arm multi-stage phase 3 clinical trial is designed to rigorously evaluate a total of 4 alternative treatment options for systemic CL against Sodium Stibugluconate (SSG) as the standard of care. The trial comprises two seamlessly linked stages. In stage 1, all four investigational arms will be evaluated against the control arm for efficacy to inform the selection of the arms, based on a pre-defined efficacy threshold that will advance to stage 2, in addition to the control arm. After stage 2, the experimental interventions will be compared with SSG similar to a standard superiority trial for efficacy. The general study design in stage 1 and stage 2 will be identical; only the number of investigational arms may differ.
Patients will be randomized into the respective treatment arms at the recruitment sites of Arba Minch hospital, Boru Meda hospital and ALERT hospital in Ethiopia. Individuals will be hospitalized during the entire course of their treatment. As different arms have different treatment duration, patient hospitalization period and visit schedules will differ between arms. In total, the study will last 180 days for each participant.
Parasitological (microscopy, culture or PCR) confirmation of leishmaniasis
Age ≥4 and ≤65 years old
Need systemic treatment based on meeting at least one of the following criteria: >4 lesions/ At least one with lesion size >4cm/ Mucosal involvement, or at risk for mucosal involvement (<1 cm from the nose, eyes or vermillion border of the lips)/ Previous failure of lesion-directed treatment /Lesions on areas not suitable for lesion-directed therapy (e.g. joints, eyelids, fingers)/ Deep or extensive lesion(s) with risk of functional impairment
Informed consent provided, as follows: For patients ≥18 years of age: Patient is willing and able to provide informed consent. / For patients aged 8 to 17 years (inclusive): Parent or caregiver is willing and able to provide informed consent, and patient is willing and able to provide assent / For patients aged 4 to 7 years (inclusive): Parent or caregiver is willing and able to provide informed consent.
Pregnant (positive pregnancy test at screening) or breastfeeding
Any known severe medical comorbidities, or signs and symptoms of severe disease, that in the opinion of the investigator disqualifies the patient of being enrolled in the trial or precludes evaluation of the patient's response to the study medication. Examples are: Severe known active infections such as tuberculosis, schistosomiasis, malaria, hepatitis B virus, active hepatitis C virus/ Serious underlying disease (e.g. cardiac, renal, hepatic (including diabetes mellitus) or chronic disease/ Immunocompromising conditions: transplant patients, or patients receiving immunosuppressant medication/ Pre-existing ocular conditions evaluated at baseline: e.g. keratitis, uveitis, scleritis/ Pre-existing sensorineural hearing loss evaluated at baseline, or previously diagnosed with ototoxicity
HIV Infection
Severe malnutrition: ≤5 years old: Mean upper arm circumference (MUAC) <115mm/ 6-10 years old: MUAC <135mm/ 11-17 years old: MUAC <160mm/ ≥ 18 years old: Body mass index (BMI) <16kg/m²
Institute of Tropical Medicine, Belgium
Lead sponsor
London School of Hygiene and Tropical Medicine
Collaborator
Uppsala University
Collaborator
University of Stellenbosch
Collaborator
Armauer Hansen Research Institute, Ethiopia
Collaborator
Wollo University
Collaborator
Arba Minch University
Collaborator