Tofacitinib Associated With Meglumine Antimoniate in Cutaneous Leishmaniasis (CLTofa23)

Tofacitinib Associated With Meglumine Antimoniate in the Control of American Tegumentary Leishmaniasis. A Randomized and Controlled Clinical Trial.

Phase 2/3 randomized and controlled clinical trial, which will evaluate the effectiveness of the association meglumine antimoniate (Glucantime) with tofacitinib in the cure of CL and the capacity of this association to reduce the time of cure of the disease.

Study Overview

• Status: Not yet recruiting
• Conditions: Cutaneous Leishmaniasis, American
• Intervention / Treatment: Drug: Parenteral meglumine antimoniate; Drug: Oral tofacitinib

Detailed Description

1. STUDY AREA The southeastern region of the State of Bahia, Brazil, where the village of Corte de Pedra and adjacent towns are located, is one of the most important American Tegumentary Leishmaniasis (ATL) endemic area in Latin America. The Corte de Pedra Health Center, in the municipality of Tancredo Neves, is located 280km from Salvador and is a Reference Center for Diagnosis and Treatment of ATL. Yearly, more than 500 cases of patients with ATL are diagnosed and treated at this Center.

   The Health Center was established in 1986 and clinical physicians, dermatologists, otorhinolaryngologists and immunologists from the Immunology Service of the Federal University of Bahia, the Gonçalo Moniz Institute (IGM) and the Federal University of Recôncavo Bahiano (UFRB) visit the area every two weeks. The Post also has the support of 4 trained health agents, all residents of the region. They assist patients, visit families, and participate in research activities.

2. STUDY DESIGN

   A. Type of study:

   This project is a phase 2/3 randomized and controlled clinical trial, which will evaluate the effectiveness of the association meglumine antimoniate (Glucantime) with tofacitinib in the cure of CL. the main objectives are: 1. To compare the cure rate of meglumine antimoniate associated with tofacitinib with meglumine antimoniate alone in the treatment of CL caused by L. braziliensis; 2. To determine whether combined treatment with meglumine antimoniate associated with tofacitinib reduces CL healing time.

   B. Definition of cases:

   Cutaneous Leishmaniasis: Presence of a typical ulcerated lesion on the skin, without evidence of mucosal involvement, with a positive skin test and disease duration between 30 and 90 days. The diagnosis will be made by identifying amastigotes in the histopathological study with immunohistochemistry and/or documentation of DNA for L.braziliensis by polymerase chain reaction (PCR).

   C. Methodology:

   The rate of cure or treatment failure is only defined on day 90 after starting therapy. We estimate that combining Glucantime with tofacitinib will increase the healing rate and reduce the healing time of CL. The present proposal is a proof of concept with the participation of patients with CL with disease duration between 30 and 90 days and with ulcer size between 10 and 60mm. Patients will be randomized, group 1 will receive Glucantime at a dose of 20mg/Kg/weight /day with a maximum dose of 1200mg intravenously for 20 days, and group 2 will be treated with Glucantime at the dose and time period described above associated with tofacitinib at a dose of 10mg/day for 30 days. Patients will be evaluated on day 0, day 30, day 60 and day 90 to determine the size and characteristics of the ulcers and the occurrence of wound healing.

   Sample size calculation: Considering that healing of ulcers up to 60mm in diameter in patients with CL with Glucantime will occur in 50% of patients while the cure rate in patients receiving Glucantime combined with tofacitinib will be 90% with a power of 80% and P< 0.05, 22 patients will be needed, 11 in each group.

   Subjects will be allocated in the 2 study arms after randomization at www.randomization.com.

3. ETHICAL CONSIDERATIONS Participation in the study is voluntary and all participants must, after reading and understanding the nature of the study, benefits and risks, sign the attached Free and Informed Consent Form (TCLE). This study was approved by the ethics committee of the Faculty of Medicine of Bahia, Federal University of Bahia.

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: EDGAR L CARVALHO, MD, PhD; Phone Number: 7132377353; Email: imuno@ufba.br
• Study Contact Backup: Name: PAULO R LIMA MACHADO, MD, PhD; Phone Number: 7132377353; Email: 19pmachado@gmail.com

Study Locations

• Brazil
  • Bahia
    • Presidente Tancredo Neves, Bahia, Brazil, 40000
      • Corte de Pedra Health Post

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects with CL of both sexes with disease duration between 30 and 90 days. Patients with CL will be treatment-naïve for leishmaniasis. Individuals will be explained about the nature of the study and will only be included if they agree to participate and sign the Free and Informed Consent Form.

Exclusion Criteria:

• Patients under the age of 18 and pregnant women will not participate in the study considering the need to withdraw 30 ml of blood to carry out the studies of the immune response. Patients over 60 years old, debilitating chronic diseases such as heart failure, liver failure, kidney failure, HIV infection and use of immunosuppressant drugs will also not participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo and Sbv; Eleven CL patients will receive meglumine antimoniate by EV route at 20mg/kg/day, for 20 days.	Drug: Parenteral meglumine antimoniate; Meglumine antimoniate
Experimental: Tofacitinib and Sbv; Eleven CL patients will receive oral tofatinib (10mg daily for 30 days) associated to meglumine antimoniate by EV route at 20mg/kg/day, for 20 days.	Drug: Parenteral meglumine antimoniate; Meglumine antimoniate; Drug: Oral tofacitinib; Association of tofacitinib and meglumine antimoniate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cure at 90 days	Healing will be defined by complete healing of the ulcer and re-epithelialization of the skin on day 90, in the absence of infiltrated borders. Failure will be defined as persistence of the ulcer at day 90 with ulcer healing occurring but persistent infiltration at the edges.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cure at 180 days	Absence of relapse after 180 days	180 days
Time to cure	Time (in days) until complete healing of the ulcer and re-epithelialization of the skin in the absence of infiltrated borders.	Days
Adverse events	Adverse events will be recorded and graded	45 dyas

Collaborators and Investigators

• Sponsor: Hospital Universitário Professor Edgard Santos
• Collaborators: Instituto Gonçalo Muniz FIOCRUZ BA
• Investigators: Principal Investigator: EDGAR CARVALHO, MD, PhD, Federal University of Bahia

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: August 21, 2023
• First Submitted That Met QC Criteria: August 21, 2023
• First Posted (Actual): August 25, 2023

Study Record Updates

• Last Update Posted (Actual): August 25, 2023
• Last Update Submitted That Met QC Criteria: August 21, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Cutaneous Leishmaniasis, meglumine antimoniate, tofacitinib
• 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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Protein Kinase Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Janus Kinase Inhibitors; Tofacitinib; Meglumine Antimoniate
• Other Study ID Numbers: CL Tofa23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is not a plan to make IPD available.

Drug and device information, study documents

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