<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/NCT03033316</url>
  </required_header>
  <id_info>
    <org_study_id>14-097</org_study_id>
    <nct_id>NCT03033316</nct_id>
  </id_info>
  <brief_title>A Evaluation of the Safety of Oncocort IV Pegylated Liposomal Dexamethasone Phosphate in Patients With Progressive Multiple Myeloma</brief_title>
  <acronym>AMETHYST</acronym>
  <official_title>A Phase I-IIa, Open Label, Multi-Center, Dose Escalating Study to Evaluate the Safety of Intravenous Pegylated Liposomal Dexamethasone Sodium Phosphate (Oncocort) as Monotherapy in Patients With Previously Treated Progressive Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Enceladus Pharmaceuticals BV</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Hospital, Aachen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Accelovance</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Enceladus Pharmaceuticals BV</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Oncocort Dexamethasone sodium phosphate encapsulated in so-called 'long-circulating'&#xD;
      PEGylated liposomes is in development with the prospect of providing enhanced and prolonged&#xD;
      lesion uptake of dexamethasone and therefore increased therapeutic benefit over existing&#xD;
      formulations of dexamethasone in Multiple Myeloma. The current trial is a first-in-man study&#xD;
      with Oncocort monotherapy with the objective to assess safety, tolerability, efficacy and&#xD;
      dose response after short-term treatment with repeated infusions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This open label multicenter study will evaluate the safety and efficacy of I.V. Oncocort&#xD;
      Dexamethasone sodium phosphate given as a short term induction therapy in Multiple Myeloma&#xD;
      patients. It consist of a Phase 1 part with a maximum number of 5 ascending dose levels while&#xD;
      additional patients will be treated in the Phase 2a part with the recommended phase 2 dose to&#xD;
      obtain additional safety data and preliminary efficacy data in multiple myeloma patients. For&#xD;
      the dose escalation phase 1 part, 3 patients per dose level will be enrolled. If one patient&#xD;
      reaches DLT, another 3 patients will be enrolled in the same dose level. If two or more&#xD;
      patients reach DLT in one dose level, maximum tolerated dose (MTD) is defined at the last&#xD;
      dose level beneath DLT. Not more than 5 dose level groups are anticipated for this part of&#xD;
      the study. MTD will be the Recommended Phase II Dose (RPTD) for the phase IIa part of the&#xD;
      study. For the phase 2a part, 7 additional patients will be enrolled at the RPTD dose level,&#xD;
      bringing the total number of patients monitored for responses at this dose level to at least&#xD;
      10.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Patient enrolment issues&#xD;
  </why_stopped>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">August 2020</completion_date>
  <primary_completion_date type="Actual">August 2020</primary_completion_date>
  <phase>Phase 1/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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>Week 8</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response according to IMWG Criteria</measure>
    <time_frame>4 and 8 weeks after 1st dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage change of myeloma-related measures</measure>
    <time_frame>up to 8 weeks after 1st dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life questionnaire</measure>
    <time_frame>up to 8 weeks after 1st dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Plasma Concentration (Cmax)</measure>
    <time_frame>during 1st 4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC)</measure>
    <time_frame>during 1st 4 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>IV Liposomal Dexamethasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IV Liposomal Dexamethasone given 1 to 4 times in total over period of maximally 4 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <arm_group_label>IV Liposomal Dexamethasone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Previously diagnosed symptomatic MM according to International Myeloma Working Group&#xD;
             (IMWG) criteria 1.1. Previously treated with at least two therapy lines including at&#xD;
             least one proteasome-inhibitor and at least one immunomodulatory drug 1.2. Relapse&#xD;
             after or progressive disease under last therapy according to IMWG criteria.&#xD;
&#xD;
          2. At least 18 years old&#xD;
&#xD;
          3. Measurable disease (M-protein and/or free light chains) in serum and/or urine&#xD;
&#xD;
          4. Willing and able to comply the study protocol visits and assessments&#xD;
&#xD;
          5. Willing to use highly effective methods of birth control (see section 7.1.3)&#xD;
&#xD;
          6. Written informed consent prior to study participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Types of Multiple Myeloma previously shown to be irresponsive to dexamethasone&#xD;
             monotherapy during the last 6 months&#xD;
&#xD;
          2. Plasma cell leukemia&#xD;
&#xD;
          3. Subject with positive hepatitis panel (including hepatitis B surface antigen [HBsAg],&#xD;
             and / or anti-hepatitis B core antibodies, and / or hepatitis C virus antibody&#xD;
             [anti-HCV]), and / or a positive HIV antibody screen&#xD;
&#xD;
          4. Severe abnormal organ function function or laboratory results at the time of the&#xD;
             Screening Visit: WBC &lt;3.0 g/L, ANC &lt;1.5 G/L, PLT &lt;50 G/L, Sodium &lt;135 mmol/L or &gt;150&#xD;
             mmol/L, potassium &lt;3.5 mmol/L or &gt;5.5 mmol/L, calcium &lt;2.0 mmol/L or &gt; 2.9mmol/L,&#xD;
             phosphorus &lt;0.8 mmol/L, total bilirubin &gt;1.5x ULN, AP &gt;2.5x ULN, gammaGT &gt;3x ULN, ALT&#xD;
             &gt;3x ULN, CK &gt;2.5x ULN, Creatinine &gt;2x ULN, fasting glucose &gt;250 mg/dL, albumin &lt;3&#xD;
             g/dL, cholesterol &gt; 300 mg/dL&#xD;
&#xD;
          5. Treatment with oral or injectable (including intra-articular) corticosteroids (CS)&#xD;
             within 4 weeks prior to Screening Visit. Inhaled and dermal corticosteroid&#xD;
             formulations are allowed&#xD;
&#xD;
          6. Subjects who have received a chemotherapeutic treatment cycle including dexamethasone&#xD;
             within 4 weeks prior to the Screening Visit&#xD;
&#xD;
          7. Known sensitivity to any component of the study drug or previous hypersensitivity&#xD;
             reaction or other clinically significant reaction to intravenous medications, biologic&#xD;
             therapy or IV radiocontrast agents&#xD;
&#xD;
          8. Active infection requiring systemic treatment&#xD;
&#xD;
          9. Planned major surgery during the study period or had undergone major surgery within 30&#xD;
             days prior to the Screening visit&#xD;
&#xD;
         10. Pregnancy or breastfeeding&#xD;
&#xD;
         11. Any clinically significant hepatic, renal, cardiac, pulmonary, gastrointestinal,&#xD;
             metabolic or endocrine disturbances, other medical or psychiatric condition, or&#xD;
             clinically relevant abnormal values on any investigation, in the opinion of the&#xD;
             Investigator, that could make the subject unsuitable for the study, could compromise&#xD;
             subject safety, limit the subject's ability to complete the study, and/or compromise&#xD;
             the objectives of the study, including severe neuropathies or other painful conditions&#xD;
             that might interfere with pain evaluation&#xD;
&#xD;
         12. Participation in another clinical investigation less than 4 weeks prior to inclusion&#xD;
&#xD;
         13. The subject has a history of any other illness, which, in the opinion of the&#xD;
             Investigator, might pose an unacceptable risk by administering study medication.&#xD;
&#xD;
         14. The subject has any current or past medical condition and/or required medication to&#xD;
             treat a condition that could affect the evaluation of the study&#xD;
&#xD;
         15. The subject is unwilling or unable to follow the procedures outlined in the protocol&#xD;
&#xD;
         16. The subject is mentally or legally incapacitated&#xD;
&#xD;
         17. Persons who are in a relationship of dependence to the Investigator or the Sponsor&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stefan Wilop, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>RWTH University Clinic Aachen</affiliation>
  </overall_official>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>January 3, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>November 4, 2020</last_update_submitted>
  <last_update_submitted_qc>November 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 6, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Multiple Myeloma</keyword>
  <keyword>Liposomal Dexamethasone</keyword>
  <keyword>Targeted Drug Delivery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</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/NCT03033316
org study id: 14-097
nct id: NCT03033316
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Oncocort Dexamethasone sodium phosphate encapsulated in so-called 'long-circulating'
      PEGylated liposomes is in development with the prospect of providing enhanced and prolonged
      lesion uptake of dexamethasone and therefore increased therapeutic benefit over existing
      formulations of dexamethasone in Multiple Myeloma. The current trial is a first-in-man study
      with Oncocort monotherapy with the objective to assess safety, tolerability, efficacy and
      dose response after short-term treatment with repeated infusions.
This open label multicenter study will evaluate the safety and efficacy of I.V. Oncocort
      Dexamethasone sodium phosphate given as a short term induction therapy in Multiple Myeloma
      patients. It consist of a Phase 1 part with a maximum number of 5 ascending dose levels while
      additional patients will be treated in the Phase 2a part with the recommended phase 2 dose to
      obtain additional safety data and preliminary efficacy data in multiple myeloma patients. For
      the dose escalation phase 1 part, 3 patients per dose level will be enrolled. If one patient
      reaches DLT, another 3 patients will be enrolled in the same dose level. If two or more
      patients reach DLT in one dose level, maximum tolerated dose (MTD) is defined at the last
      dose level beneath DLT. Not more than 5 dose level groups are anticipated for this part of
      the study. MTD will be the Recommended Phase II Dose (RPTD) for the phase IIa part of the
      study. For the phase 2a part, 7 additional patients will be enrolled at the RPTD dose level,
      bringing the total number of patients monitored for responses at this dose level to at least
      10.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: Week 8
measure: Response according to IMWG Criteria
time frame: 4 and 8 weeks after 1st dose
measure: Percentage change of myeloma-related measures
time frame: up to 8 weeks after 1st dose
measure: Quality of life questionnaire
time frame: up to 8 weeks after 1st dose
measure: Peak Plasma Concentration (Cmax)
time frame: during 1st 4 weeks
measure: Area under the plasma concentration versus time curve (AUC)
time frame: during 1st 4 weeks
arm group label: IV Liposomal Dexamethasone
arm group type: Experimental
description: IV Liposomal Dexamethasone given 1 to 4 times in total over period of maximally 4 weeks
intervention type: Drug
intervention name: Dexamethasone
arm group label: IV Liposomal Dexamethasone
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Stefan Wilop, MD
role: Principal Investigator
affiliation: RWTH University Clinic Aachen
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
sharing ipd: No