Randomised Clinical Trial for New Treatment Modalities for Cutaneous Leishmaniasis Caused by Leishmania Tropica, in Pakistan

Randomised, Open Label, Multicentre, Non-inferiority Clinical Trial for New Treatment Modalities for Cutaneous Leishmaniasis Caused by Leishmania Tropica, in Pakistan

randomised control clinical trial to evaluate miltefosine, thermotherapy and the combination miltefosine-thermotherapy are effective, safe and tolerable alternative treatment options to treat cutaneous leishmaniasis caused by L. tropica, in Pakistan compared to the standard of care.

Study Overview

• Status: Unknown
• Conditions: Old World Cutaneous Leishmaniasis
• Intervention / Treatment: Combination product: drug: miltefosine with thermotherapy

Detailed Description

Until now, there is no well-established evidence based option to treat CL caused by the Leishmania tropica, besides antimonial injections. Alternative treatment options are not available in Pakistan, or there is limited evidence of the effectivity.

Effectiveness of thermotherapy in L. tropica is studied in only three studies in OWCL with a variable cure rate (54.1% - 98%). But it could be an attractive option, because only one treatment session is required and studies report less scarring tissue. Another promising treatment option is oral miltefosine. There is considerable evidence in the literature of the efficacy of miltefosine in treatment of CL caused by L. major, however no studies have been conducted to evaluate the efficacy in CL caused by L. tropica species. This oral treatment could have major benefits for CL patients as it can be provided in peripheral health facilities and to patients who have contraindications to antimony treatment (elderly, and patients with cardiac or renal disease, or diabetes). A combination of thermotherapy and miltefosine, the advantages offered by this combination are that a) the use of a topical plus a systemic treatment would hypothetically have an additive effect of two treatments with different modes of action. For the reason that systemic treatment could eliminate those circulating or remaining parasites located in the periphery of the lesion that topical treatment fails to remove, which might be the cause of a relapse, b) it may reduce the necessary length of treatment with miltefosine. For these above reasons, in a prospective trial we aim to evaluate the effectiveness and safety of thermotherapy, miltefosine and the combination of thermotherapy and miltefosine in CL caused by L. tropica, with the objective to find a treatment with an efficacy which is non-inferior to the standard of care with antimony injections.

• Study Type: Interventional
• Enrollment (Anticipated): 832
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Suzette Kämink; Phone Number: +31687680573; Email: s.s.kamink@gmail.com
• Study Contact Backup: Name: Koert Ritmeijer; Phone Number: +31205208767; Email: koert.ritmeijer@oca.msf.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female patients with clinical and laboratory confirmed CL, and who can be treated with localised intralesional antimonial injections and/or thermotherapy:
• lesion size ≥0.5 cm and ≤4 cm
• not located on the ear, nose, near to the eye or mucosal membranes, on joints, or on a location that in the opinion of the principle investigator (PI) is difficult to apply thermotherapy (TT) or intralesional (IL) injections
• patient with ≤4 lesions
• duration of lesions less than five months by patient history
• Patients who have signed the informed consent form.

Exclusion Criteria:

• Pregnant women and breast feeding women
• Non-pregnant women in reproductive age refusing effective (injectable) contraception for a period of five months
• Patients <10years old
• Patients who cannot be treated with localised IL antimonial injections or TT (patients with more than 4 lesions, lesions >4cm in diameter, or located on joints, lips, nose, ears or near eyes)
• History of clinically significant medical problems or treatment that might interact with the study treatment and interact with wound healing, such as diabetes, vascular diseases and any immunocompromising condition
• Within eight weeks of trial D1 received treatment for leishmaniasis with any medication
• History of known or suspected hypersensitivity of idiosyncratic reactions to trial medication or excipients
• Has laboratory values at screening: serum creatinine above normal level; ALT 3 times above normal range
• Patient who is not willing to attend the trial visits, or is not able to comply with follow-up visits up to three months.
• Known history of drug addiction and/or alcohol abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: monotherapy miltefosine; Miltefosine capsules (Impavido®) 2.5 mg/kg daily PO for 28 days <30 kg BW allometric miltefosine dose based on fat-free mass. (approx. 2.5 mg/kg); >30 - ≤44kg BW: 100 mg/day BID; ≥45kg BW 150mg TDS	Combination product: drug: miltefosine with thermotherapy; see previous; Other Names: device ThermoMed 1.8
EXPERIMENTAL: Thermotherapy; Thermotherapy (ThermoMed 1.8 ®) 50°C for 30 seconds, 1 session	Combination product: drug: miltefosine with thermotherapy; see previous; Other Names: device ThermoMed 1.8
EXPERIMENTAL: Combination miltefosine and thermotherapy; Miltefosine capsules 2.5 mg/kg daily PO for 21days, and thermotherapy 50°C for 30 seconds, one session on day 1 of the miltefosine.	Combination product: drug: miltefosine with thermotherapy; see previous; Other Names: device ThermoMed 1.8
ACTIVE_COMPARATOR: ° Meglumine antimoniate (Glucantime®) intralesional; Meglumine antimoniate (Glucantime®) intralesional injections 0.5-3ml, 8 sessions, bi-weekly	Combination product: drug: miltefosine with thermotherapy; see previous; Other Names: device ThermoMed 1.8

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The initial clinical cure rate in each study arm	Initial Cure: Ulcerated lesions: 100% re-epithelialization of the lesion(s) Non-Ulcerated lesions: flattening and/or no signs of induration of the lesion(s) by Day 91.	by Day 91.
Adverse events	Frequency, severity and seriousness of AEs by treatment group	by Day 91.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
initial cure and no relapse	The proportion of patients in each study arm who have fulfilled the criteria of initial cure and have no relapse	initial cure at D91 and have no relapse by D120.
100% re-epithelialized/ flattened	The number of patients with lesions 100% re-epithelialized/ flattened at each measurement time point.	at visit until D120

Collaborators and Investigators

• Sponsor: Medecins Sans Frontieres, Netherlands
• Investigators: Study Director: Koert Ritmeijer, Medecins Sans Frontieres, Netherlands

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): February 1, 2021
• Primary Completion (ANTICIPATED): July 31, 2022
• Study Completion (ANTICIPATED): December 30, 2022

Study Registration Dates

• First Submitted: February 11, 2020
• First Submitted That Met QC Criteria: February 11, 2020
• First Posted (ACTUAL): February 13, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 18, 2020
• Last Update Submitted That Met QC Criteria: June 17, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: miltefosine; Thermotherapy
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Euglenozoa Infections; Leishmaniasis; Leishmaniasis, Cutaneous; Anti-Infective Agents; Antineoplastic Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Miltefosine
• Other Study ID Numbers: CL_RCT_MF_vs_TT_2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Plan need to be made what wilkl be shared with whom (such as study protocol, SAP, ICF etc)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No