<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/NCT03829917</url>
  </required_header>
  <id_info>
    <org_study_id>AB-2018-02</org_study_id>
    <nct_id>NCT03829917</nct_id>
  </id_info>
  <brief_title>Oral Miltefosine Plus Topical Paromomycin In American Cutaneous Leishmaniasis</brief_title>
  <official_title>Oral Miltefosine Plus Topical Paromomycin In American Cutaneous Leishmaniasis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundacion Nacional de Dermatologia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hospital Dermatológico de Jorochito</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ministerio de Salud de Bolivia, Programa Nacional de Leishmaniasis</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Alfred Berman Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Fundacion Nacional de Dermatologia</source>
  <oversight_info>
    <has_dmc>No</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>
      Cure rate for L braziliensis bolivian CL has been 70%-80% for standard systemic and local&#xD;
      monotherapies. It would benefit patients if cure rates could be consistently &gt;90%, so testing&#xD;
      a combination of two treatments is proposed. The most attractive systemic therapy is the only&#xD;
      oral agent, miltefosine during 28 days, and the most attractive local therapy is application&#xD;
      of Paromomycin cream for 28 days.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cutaneous leishmaniasis (CL) is endemic in the New World from approximately the US-Mexican&#xD;
      border through Central America and the Northern part of South America down to the level of&#xD;
      Rio de Janeiro.&#xD;
&#xD;
      L braziliensis CL is perhaps the most important of these diseases, since its natural cure&#xD;
      rate is low and it may metastasize, and our group has been evaluating therapies for L&#xD;
      braziliensis in Bolivia for some time.&#xD;
&#xD;
      In recent studies at investigator's Bolivian site for the years 2013-2016, the cure rate for&#xD;
      L braziliensis CL has been 70%-80% for standard systemic and local therapies. Systemic agents&#xD;
      intramuscular pentavalent antimony cured 80% (114 of 143) and oral miltefosine cured 81% (47&#xD;
      of 58). Local injections with pentamidine cured 72% (43 of 60); intralesional antimony cured&#xD;
      70% (21 of 30). In contrast, cryotherapy was ineffective [20% (4 of 20) cured and placebo&#xD;
      creams cured 17% (5 of 30) in one report and 10% more recently.&#xD;
&#xD;
      Investigator's have recently evaluated treatment with topical paromomycin cream.&#xD;
      Paromomycin-in-Aquaphilic had a cure rate of 77.5% (31 of 40 patients) compared to a cure&#xD;
      rate of only 10% (2 of 20 patients) for the Aquaphilic vehicle alone. This remarkably high&#xD;
      cure rate, combined with essentially no adverse events (both Paromomycin-Aquaphilic and&#xD;
      Aquaphilic vehicle had only grade 1 adverse reactions in 5-10% of patients), makes&#xD;
      Paromomycin-Aquaphilic very attractive for Bolivian CL.&#xD;
&#xD;
      It would benefit patients if cure rates could be consistently &gt;90%. Since all the individual&#xD;
      therapies, whether systemic, local injections, or local cream, have an approximately 75% cure&#xD;
      rate, we propose testing a combination of two treatment. The most attractive systemic therapy&#xD;
      is the only oral agent, miltefosine, and the most attractive local therapy is simple&#xD;
      application of Paromomycin cream. Thus the present protocol proposes to evaluate the efficacy&#xD;
      of miltefosine, 2.5 mg/kg (50 mg tid) for 28 days, plus Paromomycin-Aquaphilic daily for 28&#xD;
      days. The controls will be the two components of this combination used separately:&#xD;
      miltefosine alone, Paromomycin-Aquaphilic alone.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2019</start_date>
  <completion_date type="Actual">December 31, 2020</completion_date>
  <primary_completion_date type="Actual">December 1, 2020</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Size of cutaneous ulcers</measure>
    <time_frame>2, 3, 4 and 6 months after the begining of therapy.</time_frame>
    <description>Complete healing of all lesions by 6 months after the beginning of therapy. Thus for a patient to be cured: no lesion could enlarge by 50%, relapse, or heal incompletely; and no new Leishmania-positive lesion can have appeared.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Cutaneous Leishmaniasis, American</condition>
  <arm_group>
    <arm_group_label>Paromomycin and Miltefosine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Paromomycin-Aquaphilic cream applied topically once daily for 28 days plus oral miltefosine pills 2.5 mg/day [50 mg tid] for 28 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Miltefosine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Miltefosine pills alone [2.5 mg/day [50 mg tid] for 28 days. This group will also receive Aquaphilic-vehicle cream for 28 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Paromomycin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Paromomycin-Aquaphilic cream applied topically once daily for 28 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Miltefosine and Paromomycin</intervention_name>
    <description>28 days of miltefosine plus 28 days of Paromomycin cream</description>
    <arm_group_label>Paromomycin and Miltefosine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>miltefosine</intervention_name>
    <description>28 days of miltefosine</description>
    <arm_group_label>Miltefosine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>paromomycin</intervention_name>
    <description>28 days of paromomycin creaam</description>
    <arm_group_label>Paromomycin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion and exlusion Criteria:&#xD;
&#xD;
          -  Gender: Male or female&#xD;
&#xD;
          -  Age: &gt;12 yrs of age&#xD;
&#xD;
          -  Presentation: 1-to-2 ulcerative lesions, each &lt; 30 mm in largest diameter and with a&#xD;
             total lesion area &lt;900 mm2.&#xD;
&#xD;
          -  Parasitology: Parasitological confirmation of the lesion will be made by visualization&#xD;
             or culture of Leishmania from the biopsy or aspirate of the lesion.&#xD;
&#xD;
          -  Previous treatment for leishmaniasis:&#xD;
&#xD;
          -  No specific or putatively specific therapy (Sb, pentamidine, amphotericin B,&#xD;
             miltefosine, imidazoles, allopurinol) in the last 3 months&#xD;
&#xD;
          -  Other diseases: No concomitant diseases by history that would be likely in the PI's&#xD;
             opinion to interact, either positively or negatively, with treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>JAIME SOTO, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fundación Nacional de Dermatología</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hopital, Dermatologico</name>
      <address>
        <city>Jorochito</city>
        <state>SC</state>
        <zip>00000</zip>
        <country>Bolivia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bolivia</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>January 30, 2019</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>February 1, 2021</last_update_submitted>
  <last_update_submitted_qc>February 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Paromomycin</mesh_term>
    <mesh_term>Miltefosine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03829917
org study id: AB-2018-02
nct id: NCT03829917
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Cure rate for L braziliensis bolivian CL has been 70%-80% for standard systemic and local
      monotherapies. It would benefit patients if cure rates could be consistently >90%, so testing
      a combination of two treatments is proposed. The most attractive systemic therapy is the only
      oral agent, miltefosine during 28 days, and the most attractive local therapy is application
      of Paromomycin cream for 28 days.
Cutaneous leishmaniasis (CL) is endemic in the New World from approximately the US-Mexican
      border through Central America and the Northern part of South America down to the level of
      Rio de Janeiro.

      L braziliensis CL is perhaps the most important of these diseases, since its natural cure
      rate is low and it may metastasize, and our group has been evaluating therapies for L
      braziliensis in Bolivia for some time.

      In recent studies at investigator's Bolivian site for the years 2013-2016, the cure rate for
      L braziliensis CL has been 70%-80% for standard systemic and local therapies. Systemic agents
      intramuscular pentavalent antimony cured 80% (114 of 143) and oral miltefosine cured 81% (47
      of 58). Local injections with pentamidine cured 72% (43 of 60); intralesional antimony cured
      70% (21 of 30). In contrast, cryotherapy was ineffective [20% (4 of 20) cured and placebo
      creams cured 17% (5 of 30) in one report and 10% more recently.

      Investigator's have recently evaluated treatment with topical paromomycin cream.
      Paromomycin-in-Aquaphilic had a cure rate of 77.5% (31 of 40 patients) compared to a cure
      rate of only 10% (2 of 20 patients) for the Aquaphilic vehicle alone. This remarkably high
      cure rate, combined with essentially no adverse events (both Paromomycin-Aquaphilic and
      Aquaphilic vehicle had only grade 1 adverse reactions in 5-10% of patients), makes
      Paromomycin-Aquaphilic very attractive for Bolivian CL.

      It would benefit patients if cure rates could be consistently >90%. Since all the individual
      therapies, whether systemic, local injections, or local cream, have an approximately 75% cure
      rate, we propose testing a combination of two treatment. The most attractive systemic therapy
      is the only oral agent, miltefosine, and the most attractive local therapy is simple
      application of Paromomycin cream. Thus the present protocol proposes to evaluate the efficacy
      of miltefosine, 2.5 mg/kg (50 mg tid) for 28 days, plus Paromomycin-Aquaphilic daily for 28
      days. The controls will be the two components of this combination used separately:
      miltefosine alone, Paromomycin-Aquaphilic alone.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change in Size of cutaneous ulcers
time frame: 2, 3, 4 and 6 months after the begining of therapy.
description: Complete healing of all lesions by 6 months after the beginning of therapy. Thus for a patient to be cured: no lesion could enlarge by 50%, relapse, or heal incompletely; and no new Leishmania-positive lesion can have appeared.
arm group label: Paromomycin and Miltefosine
arm group type: Experimental
description: Paromomycin-Aquaphilic cream applied topically once daily for 28 days plus oral miltefosine pills 2.5 mg/day [50 mg tid] for 28 days.
arm group label: Miltefosine
arm group type: Active Comparator
description: Miltefosine pills alone [2.5 mg/day [50 mg tid] for 28 days. This group will also receive Aquaphilic-vehicle cream for 28 days
arm group label: Paromomycin
arm group type: Active Comparator
description: Paromomycin-Aquaphilic cream applied topically once daily for 28 days.
intervention type: Drug
intervention name: Miltefosine and Paromomycin
description: 28 days of miltefosine plus 28 days of Paromomycin cream
arm group label: Paromomycin and Miltefosine
intervention type: Drug
intervention name: miltefosine
description: 28 days of miltefosine
arm group label: Miltefosine
intervention type: Drug
intervention name: paromomycin
description: 28 days of paromomycin creaam
arm group label: Paromomycin
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: JAIME SOTO, MD
role: Principal Investigator
affiliation: Fundación Nacional de Dermatología
facility: 
country: Bolivia
responsible party type: Sponsor
mesh term: Leishmaniasis
mesh term: Leishmaniasis, Cutaneous
mesh term: Paromomycin
mesh term: Miltefosine
sharing ipd: No