<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/NCT03807362</url>
  </required_header>
  <id_info>
    <org_study_id>Nepal CC-11050</org_study_id>
    <nct_id>NCT03807362</nct_id>
  </id_info>
  <brief_title>CC-11050 Trial in Nepalese Patients With Erythema Nodosum Leprosum</brief_title>
  <official_title>A Single Center, Open Label Pilot Study to Evaluate the Safety and Efficacy of CC-11050 in Nepalese Patients With Erythema Nodosum Leprosum</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Leprosy Mission Nepal</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Leprosy Mission Nepal</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>
      This study will be a single center, Phase 2, open-label trial to evaluate the safety and&#xD;
      efficacy of 200mg CC-11050 administered twice daily taken with food for patients with&#xD;
      moderate to severe ENL. The study will be performed in two steps: 1) to evaluate immediate&#xD;
      effect in safety and efficacy of drug in 10 males with new or new recurrent episode ENL and,&#xD;
      if found to be safe and effective by the DSMB and 2) if allowed by the DSMB, and approved by&#xD;
      relevant study stakeholders, an additional 40 ENL patients will be enrolled for up to 52&#xD;
      weeks of treatment. A safety analysis will be conducted on all patients who have received at&#xD;
      least one dose of study drug, and will include the frequency of all adverse events and&#xD;
      laboratory abnormalities as well as frequency of dose interruptions, dose reductions and&#xD;
      treatment discontinuation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 7, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">March 30, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>A single center, open label pilot study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with moderate to severe ENL with severity changes as assessed by the ENL Severity Scale.</measure>
    <time_frame>10 days, 28 days and monthly up to 1 year of treatment</time_frame>
    <description>Changes in ENL Severity Scale Score (Walker et al., PLoS Negl Trop Dis 11(7): e0005716, https://doi.org/10.1371/journal.pntd.0005716) as compared to baseline and any previous time points. Ten clinical categories contribute 0-3 points toward the total score of 0-30. An ENL patient with a total scale score of less than 9 is considered to have mild ENL, while scores &gt;9 are considered moderate to severe ENL. A minimum score of 9 is required to indicate sufficient ENL symptoms from which post-intervention reduction in score(s) can be determined meaningful improvement.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with moderate to severe ENL with decreased duration of episode(s) as assessed by standard ENL episode definition.</measure>
    <time_frame>10 days, 28 days, monthly up to 1 year of treatment and up to 1 year followup after treatment cessation.</time_frame>
    <description>Changes in ENL episode duration(s) as compared to baseline and any previous time points. By definition, if ENL symptoms are separated by time and no need of treatment for &gt;28 days, they are considered separate episodes. Recurrence is anytime another episode occurs after &gt;28 days of no prior treatment or symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with moderate to severe ENL with decreased bacterial index (BI) as assessed by slit skin smear microscopy.</measure>
    <time_frame>Enrolment and after 1 year treatment.</time_frame>
    <description>Changes in slit skin smear microscopy BI as compared to baseline. BI can range from 0-6.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with moderate to severe ENL with decreased bacterial index (BI) as assessed skin histopathology.</measure>
    <time_frame>Enrolment and after 1 year treatment.</time_frame>
    <description>Changes in skin histopathology bacterial index (BI) as compared to baseline. BI can range from 0-6.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with moderate to severe ENL with improved peripheral neuropathy as assessed by standardized monofilament and voluntary muscle tests.</measure>
    <time_frame>enrolment, 10 days, 28 days, biweekly (as needed), up to 1 year treatment, up to 1 year followup after treatment cessation</time_frame>
    <description>Changes in scores for peripheral neuropathy as indicated by monofilament and voluntary muscle tests compared from baseline and any previous time points. To check neuropathy, 7 motor function nerves and 6 sensory function nerves on each side of the body are assessed for a total 26 nerves. Each are assessed on 3 sites using a standard set of Semmes-Weinstein monofilaments. The 200mg filament and the 2g filament represent threshold for the hand and foot, respectively. The 0-5 Medical Research Council (MRC) scale is used for motor function assessment. Sensory scores &gt;3 and motor nerve scoring (MRC) &lt; 5 are regarded impaired (indicating neuropathy). More method specifics can be found here: van Veen N.H., et al., Corticosteroids for treating nerve damage in leprosy. Cochrane Database Syst Rev, 2007(2): p. CD005491.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with moderate to severe ENL with improved quality of life as assessed by the World Health Organization Quality of Life tool.</measure>
    <time_frame>Enrolment, 28 days, monthly up to 1 year of treatment and up to 1 year followup after treatment cessation.</time_frame>
    <description>Changes in scores for the World Health Organization Quality of Life assessment as compared to baseline and any previous time points. There are 26 questions in this questionnaire and each can be scored from 1 to 5 points. The highest possible score is 130 and lowest possible score is 26. A higher score denotes better quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with moderate to severe ENL as assessed by standard blood panel and basic metabolic testing.</measure>
    <time_frame>Enrolment, day 10, day 17, day 28, monthly up to 1 year of treatment, and 1 month post-cessation of treatment.</time_frame>
    <description>Abnormalities or change in values in comparison to baseline and any previous time points.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with moderate to severe ENL as assessed by urinalysis.</measure>
    <time_frame>Enrolment, day 10, day 17, day 28, monthly up to 1 year of treatment, and 1 month post-cessation of treatment.</time_frame>
    <description>Detection of albumin (qualitative) as compared to baseline and any previous time points. Urine albumin is related to ENL severity and kidney function test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with moderate to severe ENL as assessed by serological indicators associated with ENL.</measure>
    <time_frame>Enrolment, day 10, day 17, day 28, monthly up to 1 year of treatment, and 1 month post-cessation of treatment.</time_frame>
    <description>Detection of rheumatoid arthritis factor (positive) and/or C-reactive protein (positive) as compared to baseline and any previous time points.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Erythema Nodosum Leprosum</condition>
  <condition>Leprosy</condition>
  <arm_group>
    <arm_group_label>CC-11050 treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>200mg CC-11050 will be administered twice daily as a pill taken with food (at breakfast and evening meal) for participants with moderate to severe ENL for 10 days, then up to 28 days (during Step 1) and then up to 1 year (during Step 2).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CC-11050</intervention_name>
    <description>CC-11050 is a novel anti-inflammatory compound with potential to treat a variety of chronic inflammatory conditions.</description>
    <arm_group_label>CC-11050 treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Study participants must satisfy the following criteria to be enrolled in the study:&#xD;
&#xD;
          1. Must be 18 -65 years old, weight &gt; 35kg for women and &gt;40kg for men at the time of&#xD;
             signing the informed consent.&#xD;
&#xD;
          2. Understand and voluntarily sign an informed consent document prior to any study&#xD;
             related assessments/procedures are conducted.&#xD;
&#xD;
          3. Have signs or symptoms of new or new episode ENL. In Step one, participants must be&#xD;
             male. In Step 2, participants can be either male or female.&#xD;
&#xD;
          4. Able to adhere to the study schedule and other protocol requirements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        The presence of any of the following will exclude a participant from enrollment:&#xD;
&#xD;
          1. Any significant medical condition, laboratory abnormality, or psychiatric illness that&#xD;
             would prevent the participants from participating in the study.&#xD;
&#xD;
          2. Patients on continuous rifampicin will be excluded, however, If rifampicin is given&#xD;
             only once a month as part of a multi-drug regimen, a minimum of 2-week washout period&#xD;
             is required prior to administration of CC-11050&#xD;
&#xD;
          3. Any condition including the presence of laboratory abnormalities, which places the&#xD;
             participant at unacceptable risk if he were to participate in the study.&#xD;
&#xD;
          4. Any condition that confounds the ability to interpret data from the study (ie, HIV,&#xD;
             chronic HepB, chronic HepC or TB patients under active treatment). Resolved TB&#xD;
             patients will not be excluded from the study.&#xD;
&#xD;
          5. Stable and well managed patients with Diabetes and hypertension will not be excluded&#xD;
             from the study.&#xD;
&#xD;
          6. Use of systemic corticosteroid or immunosuppressant therapy within 7 days of study&#xD;
             medication initiation&#xD;
&#xD;
          7. Pregnant or nursing females.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Males only for Step 1 (first 10 patients for testing up to 28 days of treatment). If successful, then both males and females can enroll in the second part of the study (up to 40 patients testing up to 1 year of therapy).</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mahesh Shah, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Leprosy Mission Nepal</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mahesh Shah, MD</last_name>
    <phone>+9779841203417</phone>
    <email>drmahesh_shah@yahoo.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Indra B Napit, MD</last_name>
    <email>indranapit@yahoo.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The Leprosy Mission Nepal</name>
      <address>
        <city>Kathmandu</city>
        <state>Bagmati</state>
        <zip>44700</zip>
        <country>Nepal</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Mahesh Shah, MD</last_name>
      <email>drmahesh_shah@yahoo.com</email>
    </contact>
    <contact_backup>
      <last_name>iIndra B Napit, MD</last_name>
      <email>indran@tlmnepal.org</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Anandaban Hospital</name>
      <address>
        <city>Lalitpur</city>
        <state>Bagmati</state>
        <zip>44700</zip>
        <country>Nepal</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Indra B Napit, MD</last_name>
      <phone>+9779851136027</phone>
      <email>indran@tlmnepal.org</email>
    </contact>
    <contact_backup>
      <last_name>Mahesh Shah, MD</last_name>
      <phone>+9779841203417</phone>
      <email>drmahesh_shah@yahoo.com</email>
    </contact_backup>
    <investigator>
      <last_name>Deanna A Hagge, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Nepal</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>September 14, 2018</study_first_submitted>
  <study_first_submitted_qc>January 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>July 6, 2020</last_update_submitted>
  <last_update_submitted_qc>July 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 7, 2020</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>Leprosy</mesh_term>
    <mesh_term>Erythema</mesh_term>
    <mesh_term>Erythema Nodosum</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>CC-11050</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03807362
org study id: Nepal CC-11050
nct id: NCT03807362
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study will be a single center, Phase 2, open-label trial to evaluate the safety and
      efficacy of 200mg CC-11050 administered twice daily taken with food for patients with
      moderate to severe ENL. The study will be performed in two steps: 1) to evaluate immediate
      effect in safety and efficacy of drug in 10 males with new or new recurrent episode ENL and,
      if found to be safe and effective by the DSMB and 2) if allowed by the DSMB, and approved by
      relevant study stakeholders, an additional 40 ENL patients will be enrolled for up to 52
      weeks of treatment. A safety analysis will be conducted on all patients who have received at
      least one dose of study drug, and will include the frequency of all adverse events and
      laboratory abnormalities as well as frequency of dose interruptions, dose reductions and
      treatment discontinuation.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: A single center, open label pilot study
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with moderate to severe ENL with severity changes as assessed by the ENL Severity Scale.
time frame: 10 days, 28 days and monthly up to 1 year of treatment
description: Changes in ENL Severity Scale Score (Walker et al., PLoS Negl Trop Dis 11(7): e0005716, https://doi.org/10.1371/journal.pntd.0005716) as compared to baseline and any previous time points. Ten clinical categories contribute 0-3 points toward the total score of 0-30. An ENL patient with a total scale score of less than 9 is considered to have mild ENL, while scores >9 are considered moderate to severe ENL. A minimum score of 9 is required to indicate sufficient ENL symptoms from which post-intervention reduction in score(s) can be determined meaningful improvement.
measure: Number of participants with moderate to severe ENL with decreased duration of episode(s) as assessed by standard ENL episode definition.
time frame: 10 days, 28 days, monthly up to 1 year of treatment and up to 1 year followup after treatment cessation.
description: Changes in ENL episode duration(s) as compared to baseline and any previous time points. By definition, if ENL symptoms are separated by time and no need of treatment for >28 days, they are considered separate episodes. Recurrence is anytime another episode occurs after >28 days of no prior treatment or symptoms.
measure: Number of participants with moderate to severe ENL with decreased bacterial index (BI) as assessed by slit skin smear microscopy.
time frame: Enrolment and after 1 year treatment.
description: Changes in slit skin smear microscopy BI as compared to baseline. BI can range from 0-6.
measure: Number of participants with moderate to severe ENL with decreased bacterial index (BI) as assessed skin histopathology.
time frame: Enrolment and after 1 year treatment.
description: Changes in skin histopathology bacterial index (BI) as compared to baseline. BI can range from 0-6.
measure: Number of patients with moderate to severe ENL with improved peripheral neuropathy as assessed by standardized monofilament and voluntary muscle tests.
time frame: enrolment, 10 days, 28 days, biweekly (as needed), up to 1 year treatment, up to 1 year followup after treatment cessation
description: Changes in scores for peripheral neuropathy as indicated by monofilament and voluntary muscle tests compared from baseline and any previous time points. To check neuropathy, 7 motor function nerves and 6 sensory function nerves on each side of the body are assessed for a total 26 nerves. Each are assessed on 3 sites using a standard set of Semmes-Weinstein monofilaments. The 200mg filament and the 2g filament represent threshold for the hand and foot, respectively. The 0-5 Medical Research Council (MRC) scale is used for motor function assessment. Sensory scores >3 and motor nerve scoring (MRC) < 5 are regarded impaired (indicating neuropathy). More method specifics can be found here: van Veen N.H., et al., Corticosteroids for treating nerve damage in leprosy. Cochrane Database Syst Rev, 2007(2): p. CD005491.
measure: Number of participants with moderate to severe ENL with improved quality of life as assessed by the World Health Organization Quality of Life tool.
time frame: Enrolment, 28 days, monthly up to 1 year of treatment and up to 1 year followup after treatment cessation.
description: Changes in scores for the World Health Organization Quality of Life assessment as compared to baseline and any previous time points. There are 26 questions in this questionnaire and each can be scored from 1 to 5 points. The highest possible score is 130 and lowest possible score is 26. A higher score denotes better quality of life.
measure: Number of participants with moderate to severe ENL as assessed by standard blood panel and basic metabolic testing.
time frame: Enrolment, day 10, day 17, day 28, monthly up to 1 year of treatment, and 1 month post-cessation of treatment.
description: Abnormalities or change in values in comparison to baseline and any previous time points.
measure: Number of participants with moderate to severe ENL as assessed by urinalysis.
time frame: Enrolment, day 10, day 17, day 28, monthly up to 1 year of treatment, and 1 month post-cessation of treatment.
description: Detection of albumin (qualitative) as compared to baseline and any previous time points. Urine albumin is related to ENL severity and kidney function test.
measure: Number of participants with moderate to severe ENL as assessed by serological indicators associated with ENL.
time frame: Enrolment, day 10, day 17, day 28, monthly up to 1 year of treatment, and 1 month post-cessation of treatment.
description: Detection of rheumatoid arthritis factor (positive) and/or C-reactive protein (positive) as compared to baseline and any previous time points.
arm group label: CC-11050 treatment
arm group type: Experimental
description: 200mg CC-11050 will be administered twice daily as a pill taken with food (at breakfast and evening meal) for participants with moderate to severe ENL for 10 days, then up to 28 days (during Step 1) and then up to 1 year (during Step 2).
intervention type: Drug
intervention name: CC-11050
description: CC-11050 is a novel anti-inflammatory compound with potential to treat a variety of chronic inflammatory conditions.
arm group label: CC-11050 treatment
criteria: 
gender: All
gender based: Yes
gender description: Males only for Step 1 (first 10 patients for testing up to 28 days of treatment). If successful, then both males and females can enroll in the second part of the study (up to 40 patients testing up to 1 year of therapy).
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Mahesh Shah, MD
role: Principal Investigator
affiliation: The Leprosy Mission Nepal
last name: Mahesh Shah, MD
phone: +9779841203417
email: drmahesh_shah@yahoo.com
last name: Indra B Napit, MD
email: indranapit@yahoo.com
facility: 
status: Not yet recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Nepal
responsible party type: Sponsor
mesh term: Leprosy
mesh term: Erythema
mesh term: Erythema Nodosum
mesh term: CC-11050
sharing ipd: Undecided