xml: <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/NCT05972954</url>
    </required_header>
    <id_info>
      <org_study_id>OMT28-C0203</org_study_id>
      <nct_id>NCT05972954</nct_id>
    </id_info>
    <brief_title>OMT-28 in Patients With Primary Mitochondrial Disease (PMD) (PMD-OPTION)</brief_title>
    <acronym>PMD-OPTION</acronym>
    <official_title>A Phase 2a Safety, Tolerability, and Pharmacodynamic Study of OMT-28 in PMD Patients With Myopathy and/or Cardiomyopathy and Inflammation (PMD-OPTION)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Omeicos Therapeutics GmbH</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Omeicos Therapeutics GmbH</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>
        The goal of this clinical trial is to learn about the treatment effects of the&#xD;
        investigational new drug OMT-28 in patients with Primary Mitochondrial Disease.&#xD;
  &#xD;
        The main question[s] it aims to answer are:&#xD;
  &#xD;
          -  Is OMT-28 safe and well tolerated in this patient population?&#xD;
  &#xD;
          -  Does OMT-28 reduce Growth Differentiation Factor 15 (GDF-15) and other relevant blood&#xD;
             markers of mitochondrial dysfunction and inflammation?&#xD;
  &#xD;
          -  Does OMT-28 improve symptoms of the disease, e.g. fatigue or exercise intolerance?&#xD;
  &#xD;
        Participants will be asked to participate in 6 study visits at an experienced clinical&#xD;
        center, including physical examinations and exercise tests, and take the study medication&#xD;
        regularly once per day according to the protocol.&#xD;
  &#xD;
        Researchers will compare for every participant the results after 3 months and 6 months of&#xD;
        treatment with a preceding 3 month period of standard care treatment to investigate the&#xD;
        effects of OMT-28 on clinical parameters and a number of blood parameters.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is an open label, single-arm, multiple-phase and multicenter Phase 2a study to evaluate&#xD;
        the efficacy, safety, and pharmacokinetics of a single OMT-28 dose (24 mg given once daily)&#xD;
        in patients with Primary Mitochondrial Disease and clinical manifestation of myopathy and/or&#xD;
        cardiomyopathy.&#xD;
  &#xD;
        Patients are eligible if they have&#xD;
  &#xD;
          -  Primary Mitochondrial Disease with a documented mitochondrial transfer ribonucleic acid&#xD;
             (tRNA) point mutation, including m3243A&gt;G, m8344A&gt;G, or single mitochondrial DNA (mtDNA)&#xD;
             deletions,&#xD;
  &#xD;
          -  a clinically relevant myopathy and/or cardiomyopathy confirmed following standard&#xD;
             guidelines,&#xD;
  &#xD;
          -  a blood plasma GDF-15 concentration &gt; 1200 ng/L and &lt; 10.000 ng/L at screening&#xD;
  &#xD;
        Participation in the study is divided into 3 parts:&#xD;
  &#xD;
          -  Screening and baseline: 12 weeks&#xD;
  &#xD;
          -  Treatment: 24 weeks&#xD;
  &#xD;
          -  Safety follow-up: 4 weeks&#xD;
  &#xD;
        Total duration: 40 weeks&#xD;
  &#xD;
        Safety will be monitored throughout the study. Blood samples for safety, pharmacodynamics and&#xD;
        pharmacokinetics will be collected at every of the 6 study visits. Exercise tests&#xD;
        (6/12-minutes walking test, 5xSST), transthoracic echocardiography, patient reported outcomes&#xD;
        (e.g. Fatigue Severity Scale and Patients' Global Impression of Change (PGIC) scale) will be&#xD;
        assessed at prespecified visits. Patients will be provided with a diary to record timing of&#xD;
        drug administration and clinical symptoms while not on site. Diaries will be reviewed and&#xD;
        checked for compliance at each non-resident visit to the clinical site.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">May 22, 2023</start_date>
    <completion_date type="Anticipated">June 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">March 30, 2025</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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Responder rate</measure>
      <time_frame>12 weeks treatment vs. 12 weeks baseline</time_frame>
      <description>Number of patients (responder rate) with a between phase difference in GDF-15 of at least 20% decrease</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Treatment Emergent Adverse Events (TEAE)</measure>
      <time_frame>up to 28 weeks</time_frame>
      <description>Compare the number of TEAEs during and between evaluation phases</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Responder rate</measure>
      <time_frame>24 weeks treatment vs. 12 weeks baseline</time_frame>
      <description>Number of patients (responder rate) with a between phase difference in GDF-15 of at least 20%</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in plasma concentration of GDF-15 [ng/L]</measure>
      <time_frame>12 weeks treatment vs. 12 weeks baseline</time_frame>
      <description>GDF-15 plasma concentration during evaluation phases, change in GDF-15 concentration during evaluations phases and comparison of GDF-15 concentration between evaluation phases</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics: Ctrough [ng/ml]</measure>
      <time_frame>weeks 12, 16, 24 and 28</time_frame>
      <description>Trough plasma concentrations (Ctrough) of OMT-28</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics: Cmax [ng/ml]</measure>
      <time_frame>week 12 and week 24</time_frame>
      <description>Plasma concentration of OMT-28 approximately at Cmax and one further timepoint after single dose</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">32</enrollment>
    <condition>Primary Mitochondrial Disease</condition>
    <arm_group>
      <arm_group_label>Treatment with OMT-28</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>24mg OMT-28, oral capsule, for 12 weeks</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>OMT-28</intervention_name>
      <description>once daily</description>
      <arm_group_label>Treatment with OMT-28</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Documented mutation resulting in mitochondrial disease: mitochondrial tRNA point&#xD;
               mutations, including m3243A&gt;G, m8344A&gt;G, and single mtDNA deletions&#xD;
  &#xD;
            2. Diagnosis of Cardiomyopathy defined as LV hypertrophy and/or LVEF&lt;50% and/or late&#xD;
               gadolinium enhancement on cardiac MRI and/or Myopathy as defined by the International&#xD;
               Workshop: Outcome measures and clinical trial readiness in primary mitochondrial&#xD;
               myopathies in children and adult (Mancuso et al. 2017[8])&#xD;
  &#xD;
            3. GDF-15 between 1,200 ng/L and 10,000 ng/L at screening&#xD;
  &#xD;
            4. Ability to perform the exercise tests&#xD;
  &#xD;
          6. Willing and able to provide a signed Informed Consent, as well as written documentation&#xD;
          in accordance with country and local privacy requirements, e.g., written data protection&#xD;
          consent 7. Able and willing to comply with the requirements of this study protocol 8. Both&#xD;
          female patients, as well as, female partners of male patients who are of child-bearing&#xD;
          potential must be willing to not become pregnant for the complete duration of the study (30&#xD;
          days after the last dose of study medication).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Pregnant, breastfeeding, or unwilling to practice birth control during participation&#xD;
               in the study&#xD;
  &#xD;
            2. Presence of a condition or abnormality that in the opinion of the Investigator would&#xD;
               compromise the safety of the patient or the quality of the data&#xD;
  &#xD;
            3. Subjects with a history of cancer in the last 5 years&#xD;
  &#xD;
            4. Hypertension defined as systolic BP &gt;160 mmHg or diastolic BP &gt;100 mmHg at screening&#xD;
  &#xD;
            5. Uncontrolled Diabetes mellitus according to investigator's assessment&#xD;
  &#xD;
            6. Stroke-like episodes or seizures occurred within last 6 months&#xD;
  &#xD;
            7. Motoric abnormalities other than related to the mitochondrial disease interfering with&#xD;
               the outcome parameters&#xD;
  &#xD;
            8. History or evidence of active tuberculosis (TB) infection, any co-disease with&#xD;
               inflammatory condition (e.g., Inflammatory Bowel Disease (IBD) etc.)&#xD;
  &#xD;
            9. Patients with a positive hepatitis panel and/or positive immunodeficiency virus test&#xD;
               at screening&#xD;
  &#xD;
           10. Regular use of steroid, non-steroidal anti-inflammatory drug (NSAID), or colchicine&#xD;
               within 30 days before screening&#xD;
  &#xD;
           11. Chronic use of Metformin&#xD;
  &#xD;
           12. Use of fish oil / omega-3 fatty acid supplements within two weeks before screening&#xD;
  &#xD;
           13. Drinking more than 9 standard cups of alcohol per week and/or more than 3 standard&#xD;
               cups of alcohol per occasion&#xD;
  &#xD;
           14. Positive drug and alcohol screen (including opiates, methadone, cocaine, amphetamines&#xD;
               [including ecstasy], cannabinoids, barbiturates, benzodiazepines)&#xD;
  &#xD;
           15. Any significant hepatic disease&#xD;
  &#xD;
           16. Receiving any investigational therapy or any approved therapy for investigational use&#xD;
               within 30 days or 5 half-lives prior to screening (whichever is longer)&#xD;
  &#xD;
           17. Received any vaccines (including the booster vaccination for COVID-19) within two&#xD;
               weeks prior to Visit 1&#xD;
  &#xD;
           18. Females of childbearing potential (those who are not surgically sterilized or&#xD;
               post-menopausal for at least 1 year) are excluded from participation in the study&#xD;
               unless they agree to use adequate contraception as described in Appendix 11.4&#xD;
  &#xD;
           19. Males (including sterilized subjects) and whose female partners have child-bearing&#xD;
               potential, must agree to use male contraception (condoms) during the period from the&#xD;
               time of signing the informed consent form (ICF) through 30 days after the last dose of&#xD;
               study drug. They must agree to immediately inform the investigator if his partner&#xD;
               becomes pregnant during the study&#xD;
  &#xD;
           20. Subjects who have previously been exposed to OMT-28, whether responder or&#xD;
               non-responder.&#xD;
  &#xD;
           21. Any use of statins (HMG-CoA reductase inhibitors)&#xD;
  &#xD;
           22. Use of quinine, tacrolimus, mycophenolate mofetil, ciclosporin, serotine receptor-type&#xD;
               1 agonist, penicillin G, penicillamine (d-penicillamine), nicotinic acid (niacin),&#xD;
               colchicine, isotretinoin, and amiodarone, peroxisome proliferator-activated receptor&#xD;
               (PPAR) activators, AMP-activated protein kinase (AMPK) activators, sirtuin activators,&#xD;
               steroids, cyclooxygenase inhibitors.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>60 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Robert Fischer, MD</last_name>
      <role>Study Director</role>
      <affiliation>Omeicos Therapeutics GmbH</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Study Manager</last_name>
      <phone>+49-30-9489-4810</phone>
      <email>clinicalstudy@omeicos.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Universitätsklinikum Bonn, Sektion Neuromuskuläre Erkrankungen, Klinik und Poliklinik für Neurologie, Venusberg-Campus 1, Gebäude 80, NPP</name>
        <address>
          <city>Bonn</city>
          <zip>53127</zip>
          <country>Germany</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Cornelia Kornblum, Prof. Dr.</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Medizinisch Fakultät der Martin-Luther-Universität Halle-Wittenberg Universitätsklinik und Poliklinik für Neurologie Universitätsklinikum , Ernst-Grube-Str. 40</name>
        <address>
          <city>Halle</city>
          <zip>06120</zip>
          <country>Germany</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Alexander Mensch, Dr.</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Friedrich-Baur-Institut an der Neurologischen Klinik und Poliklinik, Klinikum der Universität München, Ludwig-Maximilians-Universität (LMU Klinikum), Ziemssenstr. 1a</name>
        <address>
          <city>Munich</city>
          <zip>80336</zip>
          <country>Germany</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Thomas Klopstock, Prof. Dr.</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>IRCCS Institute of Neurological Science of Bologna, University of Bologna, Department of Biomedical and Neuromotor Science (DIBINEM), Ospedale Bellaria Via Altura, 3</name>
        <address>
          <city>Bologna</city>
          <zip>40139</zip>
          <country>Italy</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Valerio Carelli, Prof. Dr.</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>U.O.C. di Neurologia e Malattie Neuromuscolari</name>
        <address>
          <city>Messina</city>
          <zip>98125</zip>
          <country>Italy</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Olimpia Musumeci, Dr.</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>IRCCS Istituto Neurologico Carlo Besta, SC Servizio Di Medicina Di Laboratorio - Genetica Medica E Neurogenetica, Via Celoria 11</name>
        <address>
          <city>Milano</city>
          <zip>20133</zip>
          <country>Italy</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Costanza Lamperti, Dr.</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Azienda Ospedaliero Universitaria Pisana, P.O. Santa Chiara, U.O. Neurologia, Edificio 13, Via Roma 67</name>
        <address>
          <city>Pisa</city>
          <zip>56126</zip>
          <country>Italy</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Michelangelo Mancuso, Prof. Dr.</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>UOC di neurofisiopatologia</name>
        <address>
          <city>Roma</city>
          <zip>8-00168</zip>
          <country>Italy</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Serenella Servidei, Prof. Dr.</last_name>
      </contact>
    </location>
    <location_countries>
      <country>Germany</country>
      <country>Italy</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 27, 2023</study_first_submitted>
    <study_first_submitted_qc>July 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 2, 2023</study_first_posted>
    <last_update_submitted>September 5, 2023</last_update_submitted>
    <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Myopathy</keyword>
    <keyword>Cardiomyopathy</keyword>
    <keyword>Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome</keyword>
    <keyword>Myoclonic epilepsy with ragged red fibers (MERRF)</keyword>
    <keyword>Maternally inherited diabetes and deafness (MIDD) syndrome</keyword>
    <keyword>GDF-15</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Mitochondrial Diseases</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05972954
  org study id: OMT28-C0203
  nct id: NCT05972954
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this clinical trial is to learn about the treatment effects of the
        investigational new drug OMT-28 in patients with Primary Mitochondrial Disease.
  
        The main question[s] it aims to answer are:
  
          -  Is OMT-28 safe and well tolerated in this patient population?
  
          -  Does OMT-28 reduce Growth Differentiation Factor 15 (GDF-15) and other relevant blood
             markers of mitochondrial dysfunction and inflammation?
  
          -  Does OMT-28 improve symptoms of the disease, e.g. fatigue or exercise intolerance?
  
        Participants will be asked to participate in 6 study visits at an experienced clinical
        center, including physical examinations and exercise tests, and take the study medication
        regularly once per day according to the protocol.
  
        Researchers will compare for every participant the results after 3 months and 6 months of
        treatment with a preceding 3 month period of standard care treatment to investigate the
        effects of OMT-28 on clinical parameters and a number of blood parameters.
  This is an open label, single-arm, multiple-phase and multicenter Phase 2a study to evaluate
        the efficacy, safety, and pharmacokinetics of a single OMT-28 dose (24 mg given once daily)
        in patients with Primary Mitochondrial Disease and clinical manifestation of myopathy and/or
        cardiomyopathy.
  
        Patients are eligible if they have
  
          -  Primary Mitochondrial Disease with a documented mitochondrial transfer ribonucleic acid
             (tRNA) point mutation, including m3243A>G, m8344A>G, or single mitochondrial DNA (mtDNA)
             deletions,
  
          -  a clinically relevant myopathy and/or cardiomyopathy confirmed following standard
             guidelines,
  
          -  a blood plasma GDF-15 concentration > 1200 ng/L and < 10.000 ng/L at screening
  
        Participation in the study is divided into 3 parts:
  
          -  Screening and baseline: 12 weeks
  
          -  Treatment: 24 weeks
  
          -  Safety follow-up: 4 weeks
  
        Total duration: 40 weeks
  
        Safety will be monitored throughout the study. Blood samples for safety, pharmacodynamics and
        pharmacokinetics will be collected at every of the 6 study visits. Exercise tests
        (6/12-minutes walking test, 5xSST), transthoracic echocardiography, patient reported outcomes
        (e.g. Fatigue Severity Scale and Patients' Global Impression of Change (PGIC) scale) will be
        assessed at prespecified visits. Patients will be provided with a diary to record timing of
        drug administration and clinical symptoms while not on site. Diaries will be reviewed and
        checked for compliance at each non-resident visit to the clinical site.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Responder rate
  time frame: 12 weeks treatment vs. 12 weeks baseline
  description: Number of patients (responder rate) with a between phase difference in GDF-15 of at least 20% decrease
  measure: Number of Treatment Emergent Adverse Events (TEAE)
  time frame: up to 28 weeks
  description: Compare the number of TEAEs during and between evaluation phases
  measure: Responder rate
  time frame: 24 weeks treatment vs. 12 weeks baseline
  description: Number of patients (responder rate) with a between phase difference in GDF-15 of at least 20%
  measure: Change in plasma concentration of GDF-15 [ng/L]
  time frame: 12 weeks treatment vs. 12 weeks baseline
  description: GDF-15 plasma concentration during evaluation phases, change in GDF-15 concentration during evaluations phases and comparison of GDF-15 concentration between evaluation phases
  measure: Pharmacokinetics: Ctrough [ng/ml]
  time frame: weeks 12, 16, 24 and 28
  description: Trough plasma concentrations (Ctrough) of OMT-28
  measure: Pharmacokinetics: Cmax [ng/ml]
  time frame: week 12 and week 24
  description: Plasma concentration of OMT-28 approximately at Cmax and one further timepoint after single dose
  arm group label: Treatment with OMT-28
  arm group type: Experimental
  description: 24mg OMT-28, oral capsule, for 12 weeks
  intervention type: Drug
  intervention name: OMT-28
  description: once daily
  arm group label: Treatment with OMT-28
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 60 Years
  healthy volunteers: No
  last name: Robert Fischer, MD
  role: Study Director
  affiliation: Omeicos Therapeutics GmbH
  last name: Study Manager
  phone: +49-30-9489-4810
  email: clinicalstudy@omeicos.com
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Not yet recruiting
  contact: 
  country: Germany
  country: Italy
  responsible party type: Sponsor
  mesh term: Mitochondrial Diseases