Study Comparing Several Drugs to Understand Which Work Against Cutaneous Leishmaniasis (CL)

Официальное название

A Multi-Arm, Multi-Stage Randomized Controlled Clinical Trial Evaluating Systemic Therapeutic Regimens for the Treatment of Cutaneous Leishmaniasis in Ethiopia

Обзор

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.

Вмешательства

• Препарат Sodium Stibogluconate (SSG)
  Intramuscular Administration - once daily for 28 days
• Препарат Miltefosine
  Miltefosine - Oral Administration, daily for 28 days
• Препарат Miltefosine + Paromomycin
  Miltefosine - Oral Administration, daily for 28 days + Paromomycine - Intramuscular Administration, once daily for 14 days
• Препарат Liposomal Amphotericin B (LAmB)
  Intravenous Administration, once daily on days 1, 3, 5, 7, 10, 12, 14, 17, 19, 21
• Препарат Pentamidine isethionate
  Intravenous Administration - once daily on days 1, 3, 5, 7, 9, 11, 13

Первичные конечные точки

• For each of the investigational arms (miltefosine/miltefosine + paromomycin / liposomal amphotericin B/pentamidine isethionate), to determine whether it has superior efficacy to the control arm in terms of achieving cure of all lesions at Day 90 [Срок оценки: Day 90]

Вторичные конечные точки (6)

• For each investigational arm, to determine whether it has superior efficacy to the control arm, in terms of achieving cure of all lesions at Day 180. [Срок оценки: Day 180]
• To compare between the control arm and each of the investigational arms: proportion of participants with all lesions cured, cure for all lesions considered individually, the proportion of participants whose index lesion is cured. [Срок оценки: End of Treatment, Day 42, Day 90 and Day 180]
• To compare between the control arm and each of the investigational arms: proportion of participants that reach at least substantial improvement of all lesions and the index lesion + at least substantial improvement for all lesions individually, [Срок оценки: End of Treatment, Day 42, Day 90, Day 180]
• To compare between the control arm and each of the investigational arms, the proportion of participants with treatment failure at Day 42, Day 90, and Day 180. [Срок оценки: Day 42, Day 90, Day 180]
• To assess safety by describing safety & tolerability of each arm by listing number, proportion & severity of AEs/Comparing number, proportion & reason of withdrawals and number & proportion of patients with SAEs between control and investigational arm [Срок оценки: Day 180]
• To compare between control arm and each investigational arm, the change in patient-reported outcomes over time between treatment arms [Срок оценки: Day 1, Day 42, Day 90, Day 180]

Критерии участия

Критерии включения

• 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.
• Willing and able to be hospitalized for the duration of treatment
• Willing and able to attend all follow-up visits
• If female and of child-bearing age: willing to take contraceptives during treatment and for 5 months after EoT (parenteral, intrauterine device (IUD) or implant). Note that actually taking the contraceptives is only required when randomized in an investigational arm containing miltefosine.

Критерии исключения

• 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
• (History of) ECG abnormalities: Clinically significant cardiac arrythmias: e.g. 2nd degree or 3rd degree AV block without pacemaker, sustained ventricular tachycardia/ Prolonged QTc interval >450ms
• Lab abnormalities: Haemoglobin <5.0g/dL/ Platelets <50 x 10\^9/L/ White blood count <1 x 10\^9/L / Alanine aminotransferase (AST) / aspartate aminotransferase (ALT) >3x upper limit of normal (ULN)/ Serum creatinine >1.5 x ULN/ Bilirubin >1.5 x ULN/ Fasting blood glucose (preferred) >7mmol/L (126mg/dl) or blood glucose >11.1 mmol/L (200mg/dl) at any time/ Potassium <3.5mmol/L
• Having received any allopathic treatment for CL lesion(s) in the past 6 months: cryotherapy, thermotherapy, SSG, meglumine antimoniate, paromomycin, pentamidine, liposomal amphotericin B, non-liposomal amphotericin B, miltefosine
• Diffuse cutaneous leishmaniasis (DCL)
• Patients on treatment with any of the prohibited medications, which are any treatments with the potential to influence lesion healing, skin condition, or participant safety. This includes any form of chemotherapy, antituberculosis medication, systemic antibiotics or antifungals, antivirals, corticosteroids and immunosuppressants. Topical antibiotics or antifungals are allowed as long as they are not applied on any of the CL lesions.
• Onset of lesions >24 months ago
• Known allergies or serious adverse reactions to one of the study components/medications
• Any other condition for which participation in the trial, as judged by the investigator, could compromise the well-being of the patient or prevent, limit or confound protocol-specified assessments

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Ethiopia · 3 центра

• ALERT Hospital — Addis Ababa
• Arba Minch General Hospital — Arba Minch
• Boru Meda General Hospital — Boru

Идентификаторы

NCT: NCT07463040 · MAMS4CL

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗