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/NCT06029439</url>
    </required_header>
    <id_info>
      <org_study_id>NMRA-335140-501</org_study_id>
      <secondary_id>KOASTAL-LT</secondary_id>
      <nct_id>NCT06029439</nct_id>
    </id_info>
    <brief_title>Study to Assess the Safety and Effectiveness of NMRA-335140-501</brief_title>
    <official_title>Long-term Study to Assess the Safety and Effectiveness of NMRA-335140 in Participants With Major Depressive Disorder</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Neumora Therapeutics, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Neumora Therapeutics, Inc.</source>
    <oversight_info>
      <has_dmc>Yes</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>
        This is a 52-week open-label extension (OLE) study that will evaluate the safety,&#xD;
        tolerability, and effectiveness of NMRA-335140 in participants with major depressive disorder&#xD;
        (MDD). Participants who completed a parent study investigating the efficacy of NMRA-335140 as&#xD;
        a treatment for MDD (ie, NMRA-335140-301, NMRA-335140-302, or NMRA-335140-303), who provide&#xD;
        informed consent, and who have no evidence of safety concerns that would preclude treatment&#xD;
        with NMRA-335140 may be enrolled into this extension study.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">September 2026</completion_date>
    <primary_completion_date type="Anticipated">March 2026</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>Safety and tolerability assessments based on Treatment Emergent Adverse Events (TEAEs) and validated clinical scales</measure>
      <time_frame>Up to 54 Weeks</time_frame>
      <description>An AE is any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of trial intervention, whether or not considered related to the trial intervention. Any AE occurring following the start of treatment or occurring before treatment but increasing in severity afterward were counted as treatment-emergent AE (TEAE). Clinically significant abnormalities in Clinical Laboratory Evaluations, ECGs, Vital Signs, Physical and Ophthalmological evaluations, Corneal Specular Microscopy, Columbia Suicide Severity Rating Scale (C-SSRS), and Sexual Functioning Questionnaire-14 (CSFQ-14) will be reported as TEAEs.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score over time.</measure>
      <time_frame>Baseline and up to Week 54</time_frame>
      <description>Change from baseline in MADRS total score over time will be reported. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in the Snaith-Hamilton Pleasure Scale (SHAPS) total score over time</measure>
      <time_frame>Baseline and up to Week 54</time_frame>
      <description>The SHAPS is a 14-item participant-reported instrument which measures anhedonia. It has been shown to be valid and reliable in normal and clinical samples, with adequate construct validity, satisfactory test-retest reliability, and high internal consistency. The scale will be completed by the participant and reviewed by site personnel qualified to oversee completeness. Each of the 14 items has a set of 4 responses, 2 of which endorse agreement (Definitely Agree, Agree) and 2 of which endorse disagreement (Disagree, Strongly Disagree). A total score can be derived by summing the responses; items answered with strongly agree are coded as 1 while a strongly disagree response will be coded as 4. Therefore, scores on the SHAPS can range from 14 to 56, with higher scores corresponding to higher levels of anhedonia.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in the Patient Health Questionnaire-9 (PHQ-9) total score over time.</measure>
      <time_frame>Baseline and up to Week 54</time_frame>
      <description>Change from baseline in PHQ-9 total score over time will be reported. The 9-item PHQ-9 scale scores each of the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5) diagnostic criteria for recurrent or single episode major depressive disorder (MDD) criteria and used both as a screening tool and a measure of response to treatment for depression. Each item is rated on a 4-point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in PHQ-9 Anhedonia Item #1 over time.</measure>
      <time_frame>Baseline and up to Week 54</time_frame>
      <description>The PHQ-9 is a participant-rated assessment scale for the evaluation of depression symptoms over the past 2 weeks. The PHQ-9 is a reliable and valid measure of depression and depression severity. The questionnaire consists of 9 items and each item is scored from 0 to 3. Participants will be asked how often they have been bothered by symptoms over the past 2 weeks (Not at all [0], Several days [1], More than half the time [2], or Nearly every day [3]). Higher scores indicate higher levels of depression.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in the Hamilton Anxiety Rating Scale (HAM-A) total score over time.</measure>
      <time_frame>Baseline and up to Week 54</time_frame>
      <description>The HAM-A is a clinician-rated instrument administered to assess severity of anxiety, its improvement during the course of treatment, and the timing of such improvement. This instrument will be completed by qualified and trained Investigator site raters based on a semi-structured interview for his/her assessment of the participant. The scale consists of 14 items. Each item is rated on a scale of 0 (feeling not present) to 4 (very severe prevalence of the feeling). The HAM-A total score is the sum of the 14 items and the score ranges from 0 to 56.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in the Clinical Global Impression Scale of Severity (CGI-S)</measure>
      <time_frame>Baseline and up to Week 54</time_frame>
      <description>Change from baseline in the CGI-S total score over time will be reported. The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill participants. The CGI-S permits a global evaluation of the participant's condition at a given time.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in the Clinical Global Impression Scale of Improvement (CGI-I)</measure>
      <time_frame>Baseline and up to Week 54</time_frame>
      <description>The CGI-I scale is a clinician-rated instrument that measures the improvement of the participant's symptoms of depression. It is a 7-point scale where a score of 1 indicates that the participant is &quot;very much improved,&quot; a score of 4 indicates that the participant has experienced &quot;no change,&quot; and a score of 7 indicates that the participant is &quot;very much worse.&quot;</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants whose MADRS total score decreased by greater than or equal to 50% from Baseline.</measure>
      <time_frame>Up to Week 54</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants whose MADRS total score decreased to 10 or less.</measure>
      <time_frame>Up to Week 54</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in the Sheehan Disability Scale (SDS) over time.</measure>
      <time_frame>Baseline and up to Week 54</time_frame>
      <description>The SDS is a participant-rated instrument which was developed to assess functional impairment in 3 related domains of work/school, social, and family life. It is a brief self rated tool where the participant rates the 3 items on an anchored 10 point visual analog scale. Following the participant's self assessment, the rater should review the Work/School and Days Lost items to confirm appropriateness of the selected rating by evaluating the impact of MDD symptoms across those sectors. The SDS may be administered via telephone assessment; however, the participant must be provided with a portable document format (PDF) copy of the assessment for reference of the visual analog scale when selecting their ratings.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">650</enrollment>
    <condition>Major Depressive Disorder</condition>
    <arm_group>
      <arm_group_label>NMRA-335140 80 milligrams (mg) once daily (QD)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive a NMRA-335140 tablet at a dose of 80 mg once daily (QD) during a 52-week treatment period.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>NMRA-335140</intervention_name>
      <description>Participants will receive NMRA-335140 at a dose of 80 mg once daily (QD), orally during a 52-week treatment period.</description>
      <arm_group_label>NMRA-335140 80 milligrams (mg) once daily (QD)</arm_group_label>
      <other_name>BTRX-335140</other_name>
      <other_name>CYM-53093</other_name>
      <other_name>Navacaprant</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Key Inclusion Criteria:&#xD;
  &#xD;
          Rollover participants are eligible for the study if the following inclusion criteria are&#xD;
          met:&#xD;
  &#xD;
            -  Completed a previous NMRA-335140 Phase 3 MDD study (NMRA-335140-301, NMRA-335140-302,&#xD;
               or NMRA-335140-303) according to the completion definition in the parent study&#xD;
               protocol.&#xD;
  &#xD;
            -  Signed an informed consent form (ICF) for this study.&#xD;
  &#xD;
            -  Willing to comply with the contraception requirements described in the inclusion&#xD;
               criteria of the parent study protocol.&#xD;
  &#xD;
            -  Willing to comply with the concomitant medication/therapy restrictions described in&#xD;
               the exclusion criteria of the parent study protocol.&#xD;
  &#xD;
          Key Exclusion Criteria:&#xD;
  &#xD;
          Rollover participants are excluded from the study if any of the following exclusion&#xD;
          criteria are met:&#xD;
  &#xD;
            -  Diagnosed with another Diagnostic and Statistical Manual of Mental Disorders, Fifth&#xD;
               Edition, Text Revision (DSM-5-TR) disorder that would have been exclusionary in the&#xD;
               parent study (eg, personality disorder, bipolar 1 or 2, schizophrenia, any other&#xD;
               psychotic disorder, or moderate or severe substance or alcohol use disorder [excluding&#xD;
               nicotine]).&#xD;
  &#xD;
            -  Considered to be at significant risk of suicide in the judgment of the Investigator.&#xD;
               This includes participants who are actively suicidal (eg, any suicide attempts during&#xD;
               the parent study) or are at serious suicidal risk as indicated by any current suicidal&#xD;
               intent, including a plan, as assessed by the C-SSRS (&quot;Since Last Visit&quot; version, score&#xD;
               of &quot;YES&quot; on suicidal ideation Item 4 or 5) and/or based on clinical evaluation by the&#xD;
               Investigator; or are homicidal, in the opinion of the Investigator.&#xD;
  &#xD;
            -  Non-adherent with study medication (took less than 70% of study drug over any 2-week&#xD;
               visit interval) or procedures during the parent study.&#xD;
  &#xD;
            -  Experienced treatment emergent adverse events (TEAEs) at least possibly related to the&#xD;
               study medication from the parent study and judged by the Investigator to be clinically&#xD;
               significant to render the participant ineligible for enrollment.&#xD;
  &#xD;
            -  Have an abnormality on ocular examination that would prohibit continued study&#xD;
               participation as determined by the Investigator.&#xD;
  &#xD;
            -  Use of disallowed concomitant medication or therapy that would have been exclusionary&#xD;
               in the parent study, may compromise the safety of the participant, and/or confound the&#xD;
               interpretation of protocol assessments.&#xD;
  &#xD;
            -  Considered by the Investigator to be inappropriate for any other reason.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Study Contact</last_name>
      <email>Clinicaltrials@neumoratx.com</email>
    </overall_contact>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 1, 2023</study_first_submitted>
    <study_first_submitted_qc>September 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 8, 2023</study_first_posted>
    <last_update_submitted>September 1, 2023</last_update_submitted>
    <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Major Depressive Disorder</keyword>
    <keyword>NMRA-335140</keyword>
    <keyword>Long-term</keyword>
    <keyword>Safety</keyword>
    <keyword>Efficacy</keyword>
    <keyword>Navacaprant</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Depressive Disorder</mesh_term>
      <mesh_term>Depression</mesh_term>
      <mesh_term>Depressive Disorder, Major</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT06029439
  org study id: NMRA-335140-501
  secondary id: KOASTAL-LT
  nct id: NCT06029439
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This is a 52-week open-label extension (OLE) study that will evaluate the safety,
        tolerability, and effectiveness of NMRA-335140 in participants with major depressive disorder
        (MDD). Participants who completed a parent study investigating the efficacy of NMRA-335140 as
        a treatment for MDD (ie, NMRA-335140-301, NMRA-335140-302, or NMRA-335140-303), who provide
        informed consent, and who have no evidence of safety concerns that would preclude treatment
        with NMRA-335140 may be enrolled into this extension study.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Safety and tolerability assessments based on Treatment Emergent Adverse Events (TEAEs) and validated clinical scales
  time frame: Up to 54 Weeks
  description: An AE is any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of trial intervention, whether or not considered related to the trial intervention. Any AE occurring following the start of treatment or occurring before treatment but increasing in severity afterward were counted as treatment-emergent AE (TEAE). Clinically significant abnormalities in Clinical Laboratory Evaluations, ECGs, Vital Signs, Physical and Ophthalmological evaluations, Corneal Specular Microscopy, Columbia Suicide Severity Rating Scale (C-SSRS), and Sexual Functioning Questionnaire-14 (CSFQ-14) will be reported as TEAEs.
  measure: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score over time.
  time frame: Baseline and up to Week 54
  description: Change from baseline in MADRS total score over time will be reported. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.
  measure: Change from Baseline in the Snaith-Hamilton Pleasure Scale (SHAPS) total score over time
  time frame: Baseline and up to Week 54
  description: The SHAPS is a 14-item participant-reported instrument which measures anhedonia. It has been shown to be valid and reliable in normal and clinical samples, with adequate construct validity, satisfactory test-retest reliability, and high internal consistency. The scale will be completed by the participant and reviewed by site personnel qualified to oversee completeness. Each of the 14 items has a set of 4 responses, 2 of which endorse agreement (Definitely Agree, Agree) and 2 of which endorse disagreement (Disagree, Strongly Disagree). A total score can be derived by summing the responses; items answered with strongly agree are coded as 1 while a strongly disagree response will be coded as 4. Therefore, scores on the SHAPS can range from 14 to 56, with higher scores corresponding to higher levels of anhedonia.
  measure: Change from Baseline in the Patient Health Questionnaire-9 (PHQ-9) total score over time.
  time frame: Baseline and up to Week 54
  description: Change from baseline in PHQ-9 total score over time will be reported. The 9-item PHQ-9 scale scores each of the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5) diagnostic criteria for recurrent or single episode major depressive disorder (MDD) criteria and used both as a screening tool and a measure of response to treatment for depression. Each item is rated on a 4-point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms.
  measure: Change from Baseline in PHQ-9 Anhedonia Item #1 over time.
  time frame: Baseline and up to Week 54
  description: The PHQ-9 is a participant-rated assessment scale for the evaluation of depression symptoms over the past 2 weeks. The PHQ-9 is a reliable and valid measure of depression and depression severity. The questionnaire consists of 9 items and each item is scored from 0 to 3. Participants will be asked how often they have been bothered by symptoms over the past 2 weeks (Not at all [0], Several days [1], More than half the time [2], or Nearly every day [3]). Higher scores indicate higher levels of depression.
  measure: Change from Baseline in the Hamilton Anxiety Rating Scale (HAM-A) total score over time.
  time frame: Baseline and up to Week 54
  description: The HAM-A is a clinician-rated instrument administered to assess severity of anxiety, its improvement during the course of treatment, and the timing of such improvement. This instrument will be completed by qualified and trained Investigator site raters based on a semi-structured interview for his/her assessment of the participant. The scale consists of 14 items. Each item is rated on a scale of 0 (feeling not present) to 4 (very severe prevalence of the feeling). The HAM-A total score is the sum of the 14 items and the score ranges from 0 to 56.
  measure: Change from Baseline in the Clinical Global Impression Scale of Severity (CGI-S)
  time frame: Baseline and up to Week 54
  description: Change from baseline in the CGI-S total score over time will be reported. The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill participants. The CGI-S permits a global evaluation of the participant's condition at a given time.
  measure: Change from Baseline in the Clinical Global Impression Scale of Improvement (CGI-I)
  time frame: Baseline and up to Week 54
  description: The CGI-I scale is a clinician-rated instrument that measures the improvement of the participant's symptoms of depression. It is a 7-point scale where a score of 1 indicates that the participant is "very much improved," a score of 4 indicates that the participant has experienced "no change," and a score of 7 indicates that the participant is "very much worse."
  measure: Percentage of participants whose MADRS total score decreased by greater than or equal to 50% from Baseline.
  time frame: Up to Week 54
  measure: Percentage of participants whose MADRS total score decreased to 10 or less.
  time frame: Up to Week 54
  measure: Change from baseline in the Sheehan Disability Scale (SDS) over time.
  time frame: Baseline and up to Week 54
  description: The SDS is a participant-rated instrument which was developed to assess functional impairment in 3 related domains of work/school, social, and family life. It is a brief self rated tool where the participant rates the 3 items on an anchored 10 point visual analog scale. Following the participant's self assessment, the rater should review the Work/School and Days Lost items to confirm appropriateness of the selected rating by evaluating the impact of MDD symptoms across those sectors. The SDS may be administered via telephone assessment; however, the participant must be provided with a portable document format (PDF) copy of the assessment for reference of the visual analog scale when selecting their ratings.
  arm group label: NMRA-335140 80 milligrams (mg) once daily (QD)
  arm group type: Experimental
  description: Participants will receive a NMRA-335140 tablet at a dose of 80 mg once daily (QD) during a 52-week treatment period.
  intervention type: Drug
  intervention name: NMRA-335140
  description: Participants will receive NMRA-335140 at a dose of 80 mg once daily (QD), orally during a 52-week treatment period.
  arm group label: NMRA-335140 80 milligrams (mg) once daily (QD)
  other name: BTRX-335140
  other name: CYM-53093
  other name: Navacaprant
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Study Contact
  email: Clinicaltrials@neumoratx.com
  responsible party type: Sponsor
  mesh term: Depressive Disorder
  mesh term: Depression
  mesh term: Depressive Disorder, Major
  sharing ipd: No