<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/NCT03831152</url>
  </required_header>
  <id_info>
    <org_study_id>B24CS</org_study_id>
    <nct_id>NCT03831152</nct_id>
  </id_info>
  <brief_title>Extension Study in Primary Distal Renal Tubular Acidosis</brief_title>
  <official_title>A Phase 3B Open-Label Extension Of Study B23CS (ARENA 2) Evaluating The Continued Safety And Efficacy Of ADV7103 In Subjects With Primary Distal Renal Tubular Acidosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Advicenne Pharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Advicenne Pharma</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Open-label study involving longitudinal assessment of the continued safety, tolerability, and&#xD;
      efficacy of ADV7103 in maintaining targeted serum bicarbonate levels, preventing metabolic&#xD;
      acidosis, and preventing hypokalemia in the following groups of subjects with primary dRTA:&#xD;
&#xD;
        1. subjects who participated in Study B23CS and were adherent to the protocol;&#xD;
&#xD;
        2. subjects ≥ 6 months of age who are living in Europe and did not participate in Study&#xD;
           B23CS; and&#xD;
&#xD;
        3. infants younger than 6 months of age&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">December 2023</start_date>
  <completion_date type="Anticipated">March 2025</completion_date>
  <primary_completion_date type="Anticipated">January 2025</primary_completion_date>
  <phase>Phase 3</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Safety of ADV7103 will be assessed by evaluating the frequency of Treatment-Emergent Adverse events as compared to placebo</measure>
    <time_frame>To 30 months</time_frame>
    <description>Number/proportion of subjects presenting with ADV7103 treatment-related adverse events (AEs) during the study, by severity grade.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Acidosis, Renal Tubular</condition>
  <arm_group>
    <arm_group_label>Experimental ADV7103</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients receive ADV7103 at their individualized dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ADV7103</intervention_name>
    <description>Single group assignment</description>
    <arm_group_label>Experimental ADV7103</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects who participated in Study B23CS must meet all of the following criteria to be&#xD;
        registered into this study:&#xD;
&#xD;
        1. Female or male subjects who participated in Study B23CS and were adherent to the&#xD;
        protocol;&#xD;
&#xD;
        Subjects who did not participate in Study B23CS must meet all of the following criteria to&#xD;
        be registered into this study:&#xD;
&#xD;
          1. Female or male subjects ≤ 65 years of age at time of consent with the following&#xD;
             stipulations:&#xD;
&#xD;
               1. Subjects ≥ 6 months of age must reside in Europe&#xD;
&#xD;
               2. Subjects &lt; 6 months of age must reside in the United States, Canada, or Europe;&#xD;
&#xD;
          2. Subjects &lt; 6 months of age must be able to swallow (not suck) solid food without&#xD;
             difficulty;&#xD;
&#xD;
          3. Subject presents with a previous diagnosis of primary dRTA;&#xD;
&#xD;
          4. Subject ≥ 6 months of age requires ≥ 0.9 mEq/kg/day of alkali therapy to maintain&#xD;
             serum bicarbonate levels above the LLN;&#xD;
&#xD;
          5. Urine pH &gt; 5.5 and serum bicarbonate &gt; 18 mEq/L for subjects ≥ 4 years old or &gt; 17&#xD;
             mEq/L for subjects &lt; 4 years old on alkali therapy and potassium supplementation (if&#xD;
             indicated) on at least one occasion for each within 6 months;&#xD;
&#xD;
          6. European subjects must be included in a social health insurance system and/or in&#xD;
             compliance with the recommendations of the national law in force relating to&#xD;
             biomedical research;&#xD;
&#xD;
          7. Subject or parent/guardian is willing and able to understand and sign informed consent&#xD;
             and willing to comply with protocol instructions; child assent when appropriate; and&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects who participated in Study B23CS and meet any of the following criteria will be&#xD;
        considered ineligible for registration into this study:&#xD;
&#xD;
          1. Female subject who is pregnant or lactating or has plans for pregnancy during the&#xD;
             study; or&#xD;
&#xD;
          2. Subject requires therapy with potassium sparing diuretics, angiotensin converting&#xD;
             enzyme inhibitors, angiotensin II receptor blockers, trimethoprim, drospirenone and&#xD;
             other progestins, nephrotoxic antibiotics, penicillins, tacrolimus, or medications&#xD;
             known to delay gastric emptying or otherwise interfere with absorption of study&#xD;
             product.&#xD;
&#xD;
        Subjects who did not participate in Study B23CS and meet any of the following criteria will&#xD;
        be considered ineligible for registration into this study:&#xD;
&#xD;
          1. Female subject who is pregnant or lactating or has plans for pregnancy during the&#xD;
             study;&#xD;
&#xD;
          2. Subject has evidence of proximal tubule dysfunction unless the subject is &lt; 6 months&#xD;
             of age;&#xD;
&#xD;
          3. Subject presents with another diagnosed condition as a potential etiology for her/his&#xD;
             dRTA ;&#xD;
&#xD;
          4. Subject requires therapy with potassium sparing diuretics, angiotensin converting&#xD;
             enzyme inhibitors, angiotensin II receptor blockers, trimethoprim, drospirenone and&#xD;
             other progestins, nephrotoxic antibiotics, penicillins, tacrolimus, or medications&#xD;
             known to delay gastric emptying or otherwise interfere with absorption of study&#xD;
             product;&#xD;
&#xD;
          5. Subject has evidence of obstructive uropathy or other findings on renal ultrasound&#xD;
             expected to require intervention during the course of the study;&#xD;
&#xD;
          6. Subject has any of the following laboratory abnormalities:&#xD;
&#xD;
               1. AST and/or ALT &gt; 1.5x upper limit of normal (ULN)&#xD;
&#xD;
               2. Serum potassium &gt; 5.0 mEq/L or hypokalemia accompanied by clinical symptoms (eg,&#xD;
                  muscle cramps) or significant ECG changes (eg, T wave depression, U wave&#xD;
                  elevation)&#xD;
&#xD;
               3. Estimated glomerular filtration rate (eGFR) &lt; 60 mL/min/1.73 m2 (according to the&#xD;
                  updated Schwartz formula for children and Chronic Kidney Disease - Epidemiology&#xD;
                  Collaboration [CKD-EPI] formula for adults)&#xD;
&#xD;
               4. Total bilirubin &gt; ULN, except with known Gilbert's disease.&#xD;
&#xD;
          7. Subject has been hospitalized or had outpatient surgery (other than minor skin and&#xD;
             dRTA disease-related procedures or ear tube placement) in the past 6 months or is&#xD;
             planning surgery in the next 6 months.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>4 Months</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andre Ulmann, M.D., Ph.D.</last_name>
    <role>Study Chair</role>
    <affiliation>Advicenne Pharma</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of South Florida Pediatric Infectious Diseases</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>January 23, 2019</study_first_submitted>
  <study_first_submitted_qc>February 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 5, 2019</study_first_posted>
  <last_update_submitted>May 8, 2023</last_update_submitted>
  <last_update_submitted_qc>May 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 2023</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>Acidosis, Renal Tubular</mesh_term>
    <mesh_term>Acidosis</mesh_term>
  </condition_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/NCT03831152
org study id: B24CS
nct id: NCT03831152
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Open-label study involving longitudinal assessment of the continued safety, tolerability, and
      efficacy of ADV7103 in maintaining targeted serum bicarbonate levels, preventing metabolic
      acidosis, and preventing hypokalemia in the following groups of subjects with primary dRTA:

        1. subjects who participated in Study B23CS and were adherent to the protocol;

        2. subjects ≥ 6 months of age who are living in Europe and did not participate in Study
           B23CS; and

        3. infants younger than 6 months of age
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The Safety of ADV7103 will be assessed by evaluating the frequency of Treatment-Emergent Adverse events as compared to placebo
time frame: To 30 months
description: Number/proportion of subjects presenting with ADV7103 treatment-related adverse events (AEs) during the study, by severity grade.
arm group label: Experimental ADV7103
arm group type: Experimental
description: All patients receive ADV7103 at their individualized dose
intervention type: Drug
intervention name: ADV7103
description: Single group assignment
arm group label: Experimental ADV7103
criteria: 
gender: All
minimum age: 4 Months
maximum age: 65 Years
healthy volunteers: No
last name: Andre Ulmann, M.D., Ph.D.
role: Study Chair
affiliation: Advicenne Pharma
facility: 
country: United States
responsible party type: Sponsor
mesh term: Acidosis, Renal Tubular
mesh term: Acidosis
sharing ipd: No