Fourth-generation Immucillin Derivative DI4G Associated Therapy in Cutaneous Leishmaniasis

Transition-state Analog Inhibitor of Human Purine Nucleoside Phosphorylase as an Adjunct in Cutaneous Leishmaniasis Therapy: a Randomized and Controlled Trial

A clinical trial to asses efficacy and safety of Transition-state Analog Inhibitor of Human Purine Nucleoside Phosphorylase for topical use associated standard antimonial in the treatment of Cutaneous Leishmaniasis in Bahia, Brazil.

Study Overview

• Status: Completed
• Conditions: Leishmaniasis; Leishmaniasis, Cutaneous; Leishmaniasis; American
• Intervention / Treatment: Drug: Immucillin DI4G; Drug: Meglumine antimoniate

Detailed Description

The treatment of cutaneous leishmaniasis caused by L. braziliensis in Brazil with pentavalent antimony is associated with a high rate of failure, reaching up to 45% of cases. Additionally, pentavalent antimony is only administered by parenteral route with important toxicity and ulcer lesion healing takes a long time, from 2 to 3 months.

So, this randomized and controlled clinical trial was designed to compare the efficacy and safety of standard antimonial (20mg/day /kg for 20 days) associated with Transition-state Analog Inhibitor of Human Purine Nucleoside Phosphorylase for topical use versus standard antimonial (20mg/kg/day for 20 days) associated with placebo for topical use in the treatment of Cutaneous Leishmaniasis and Early Cutaneous Leishmaniasis caused by L. braziliensis in the endemic area of Corte de Pedra, Bahia, Brazil.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Bahia
    • Corte de Pedra, Bahia, Brazil, 40000
      • Corte de Pedra Health Post

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Newly diagnosed (untreated) cutaneous leishmaniasis or early cutaneous leishmaniasis with localized lesions and a positive culture or diagnosed by polymerase chain reaction (PCR) methods or by intradermal skin testing (Montenegro test).
• Number of lesions: 1 to 3 ulcerative lesions.
• Lesion´s diameter: 1 to 5 cm.
• Disease duration: up to three months.

Exclusion Criteria:

• Aspartate aminotransferase, alanine aminotransferase >3 times upper limit of normal range
• Serum creatinine or blood urea nitrogen >1.5 times upper limit of normal range
• Evidence of serious underlying disease (cardiac, renal, hepatic or pulmonary)
• Immunodeficiency or antibody to HIV
• Any non-compensated or uncontrolled condition, such as active tuberculosis, malignant disease, severe malaria, HIV, or other major infectious diseases
• Lactation, pregnancy (to be determined by adequate test) or inadequate contraception in females of childbearing potential for treatment period plus 2 months
• Negative parasitology (aspirate/biopsy/PCR) or negative Montenegro test
• Any history of prior anti-leishmania therapy
• Any condition which compromises ability to comply with the study procedures
• Lack of ability or willingness to give informed consent (patient and/or parent / legal representative)
• Anticipated non-availability for study visits/procedure

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immucillin DI4G; Meglumine Antimoniate by intravenous route at 20mg/kg/day during 20 days + Immucillin DI4G 2% by topical use once a day at the ulcer for 20 days .	Drug: Immucillin DI4G; Immucillin DI4G was administered by topical use at 2% concentration once a day for 20 days associated with Meglumine antimoniate administered by intravenous route at a dosage of 20mg/kg/day, during 20 days.; Other Names: Fourth-generation Immucillin Derivative
Active Comparator: Meglumine Antimoniate; Meglumine Antimoniate by intravenous route at 20mg/kg/day during 20 days + placebo for topical use once a day at the ulcer for 20 days.	Drug: Meglumine antimoniate; Placebo for topical use once a day at the ulcer for 20 days associated with Meglumine antimoniate administered as the standard treatment for cutaneous leishmaniasis by intravenous route at a dosage of 20mg/kg/day, during 20 days.; Other Names: Glucantime

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cure rate or complete cicatrization of the ulcer.	Bidirectional measurements of ulcers will be taken of the patients' lesions at the initial visit, and at each follow-up visit with standardized caliper. The area involved will be calculated as the product of the two measurements. All lesions will be categorized as either active or healed (cured) at follow-up visits. Only lesions with complete re-epithelialization, without raised borders, infiltrations or crusts will be considered healed. Evaluation of the lesions will be performed by 2 clinicians who will be unaware of the group assignment of all patients.	6 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Initial cure rate or complete cicatrization of the ulcer.	Bidirectional measurements of ulcers will be taken of the patients' lesions at the initial visit, and at each follow-up visit with standardized caliper. The area involved will be calculated as the product of the two measurements. All lesions will be categorized as either active or healed (cured) at follow-up visits. Only lesions with complete re-epithelialization, without raised borders, infiltrations or crusts will be considered healed. Evaluation of the lesions will be performed by 2 clinicians who will be unaware of the group assignment of all patients.	2 months after treatment

Collaborators and Investigators

• Sponsor: Hospital Universitário Professor Edgard Santos
• Collaborators: Conselho Nacional de Desenvolvimento Científico e Tecnológico; Pontificia Universidade Católica do Rio Grande do Sul; Federal University of Bahia
• Investigators: Principal Investigator: Edgar M Carvalho, MD, PhD, Federal University of Bahia; Study Chair: Paulo RL Machado, MD, PhD, Federal University of Bahia

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: September 22, 2017
• First Submitted That Met QC Criteria: September 25, 2017
• First Posted (Actual): September 26, 2017

Study Record Updates

• Last Update Posted (Actual): September 26, 2017
• Last Update Submitted That Met QC Criteria: September 25, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Immunotherapy; Meglumine antimoniate; L.Braziliensis; Immucillin
• 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; Antiprotozoal Agents; Antiparasitic Agents; Meglumine Antimoniate
• Other Study ID Numbers: Immucillin DI4GTrial

Drug and device information, study documents

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