<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03294161</url>
  </required_header>
  <id_info>
    <org_study_id>Immucillin DI4GTrial</org_study_id>
    <nct_id>NCT03294161</nct_id>
  </id_info>
  <brief_title>Fourth-generation Immucillin Derivative DI4G Associated Therapy in Cutaneous Leishmaniasis</brief_title>
  <official_title>Transition-state Analog Inhibitor of Human Purine Nucleoside Phosphorylase as an Adjunct in Cutaneous Leishmaniasis Therapy: a Randomized and Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Universitário Professor Edgard Santos</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Conselho Nacional de Desenvolvimento Científico e Tecnológico</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Federal University of Bahia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pontificia Universidade Católica do Rio Grande do Sul</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital Universitário Professor Edgard Santos</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A clinical trial to asses efficacy and safety of Transition-state Analog Inhibitor of Human&#xD;
      Purine Nucleoside Phosphorylase for topical use associated standard antimonial in the&#xD;
      treatment of Cutaneous Leishmaniasis in Bahia, Brazil.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The treatment of cutaneous leishmaniasis caused by L. braziliensis in Brazil with pentavalent&#xD;
      antimony is associated with a high rate of failure, reaching up to 45% of cases.&#xD;
      Additionally, pentavalent antimony is only administered by parenteral route with important&#xD;
      toxicity and ulcer lesion healing takes a long time, from 2 to 3 months.&#xD;
&#xD;
      So, this randomized and controlled clinical trial was designed to compare the efficacy and&#xD;
      safety of standard antimonial (20mg/day /kg for 20 days) associated with Transition-state&#xD;
      Analog Inhibitor of Human Purine Nucleoside Phosphorylase for topical use versus standard&#xD;
      antimonial (20mg/kg/day for 20 days) associated with placebo for topical use in the treatment&#xD;
      of Cutaneous Leishmaniasis and Early Cutaneous Leishmaniasis caused by L. braziliensis in the&#xD;
      endemic area of Corte de Pedra, Bahia, Brazil.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2014</start_date>
  <completion_date type="Actual">June 2017</completion_date>
  <primary_completion_date type="Actual">April 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cure rate or complete cicatrization of the ulcer.</measure>
    <time_frame>6 months after treatment</time_frame>
    <description>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.&#xD;
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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Initial cure rate or complete cicatrization of the ulcer.</measure>
    <time_frame>2 months after treatment</time_frame>
    <description>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.&#xD;
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.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Leishmaniasis</condition>
  <condition>Leishmaniasis, Cutaneous</condition>
  <condition>Leishmaniasis; American</condition>
  <arm_group>
    <arm_group_label>Immucillin DI4G</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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 .</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Meglumine Antimoniate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Immucillin DI4G</intervention_name>
    <description>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.</description>
    <arm_group_label>Immucillin DI4G</arm_group_label>
    <other_name>Fourth-generation Immucillin Derivative</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Meglumine antimoniate</intervention_name>
    <description>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.</description>
    <arm_group_label>Meglumine Antimoniate</arm_group_label>
    <other_name>Glucantime</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Newly diagnosed (untreated) cutaneous leishmaniasis or early cutaneous leishmaniasis&#xD;
             with localized lesions and a positive culture or diagnosed by polymerase chain&#xD;
             reaction (PCR) methods or by intradermal skin testing (Montenegro test).&#xD;
&#xD;
          -  Number of lesions: 1 to 3 ulcerative lesions.&#xD;
&#xD;
          -  Lesion´s diameter: 1 to 5 cm.&#xD;
&#xD;
          -  Disease duration: up to three months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Aspartate aminotransferase, alanine aminotransferase &gt;3 times upper limit of normal&#xD;
             range&#xD;
&#xD;
          -  Serum creatinine or blood urea nitrogen &gt;1.5 times upper limit of normal range&#xD;
&#xD;
          -  Evidence of serious underlying disease (cardiac, renal, hepatic or pulmonary)&#xD;
&#xD;
          -  Immunodeficiency or antibody to HIV&#xD;
&#xD;
          -  Any non-compensated or uncontrolled condition, such as active tuberculosis, malignant&#xD;
             disease, severe malaria, HIV, or other major infectious diseases&#xD;
&#xD;
          -  Lactation, pregnancy (to be determined by adequate test) or inadequate contraception&#xD;
             in females of childbearing potential for treatment period plus 2 months&#xD;
&#xD;
          -  Negative parasitology (aspirate/biopsy/PCR) or negative Montenegro test&#xD;
&#xD;
          -  Any history of prior anti-leishmania therapy&#xD;
&#xD;
          -  Any condition which compromises ability to comply with the study procedures&#xD;
&#xD;
          -  Lack of ability or willingness to give informed consent (patient and/or parent / legal&#xD;
             representative)&#xD;
&#xD;
          -  Anticipated non-availability for study visits/procedure&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Edgar M Carvalho, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Federal University of Bahia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Paulo RL Machado, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Federal University of Bahia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Corte de Pedra Health Post</name>
      <address>
        <city>Corte de Pedra</city>
        <state>Bahia</state>
        <zip>40000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 22, 2017</study_first_submitted>
  <study_first_submitted_qc>September 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 26, 2017</study_first_posted>
  <last_update_submitted>September 25, 2017</last_update_submitted>
  <last_update_submitted_qc>September 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 26, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Universitário Professor Edgard Santos</investigator_affiliation>
    <investigator_full_name>Fernanda V Prates, MD, MSc</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Meglumine antimoniate</keyword>
  <keyword>L.Braziliensis</keyword>
  <keyword>Immunotherapy</keyword>
  <keyword>Immucillin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leishmaniasis</mesh_term>
    <mesh_term>Leishmaniasis, Cutaneous</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Meglumine Antimoniate</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03294161
org study id: Immucillin DI4GTrial
nct id: NCT03294161
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Cure rate or complete cicatrization of the ulcer.
time frame: 6 months after treatment
description: 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.
measure: Initial cure rate or complete cicatrization of the ulcer.
time frame: 2 months after treatment
description: 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.
arm group label: Immucillin DI4G
arm group type: Experimental
description: 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 .
arm group label: Meglumine Antimoniate
arm group type: Active Comparator
description: 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.
intervention type: Drug
intervention name: Immucillin DI4G
description: 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.
arm group label: Immucillin DI4G
other name: Fourth-generation Immucillin Derivative
intervention type: Drug
intervention name: Meglumine antimoniate
description: 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.
arm group label: Meglumine Antimoniate
other name: Glucantime
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Edgar M Carvalho, MD, PhD
role: Principal Investigator
affiliation: Federal University of Bahia
last name: Paulo RL Machado, MD, PhD
role: Study Chair
affiliation: Federal University of Bahia
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Hospital Universitário Professor Edgard Santos
investigator full name: Fernanda V Prates, MD, MSc
investigator title: Principal Investigator
mesh term: Leishmaniasis
mesh term: Leishmaniasis, Cutaneous
mesh term: Meglumine Antimoniate