<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/NCT04476446</url>
  </required_header>
  <id_info>
    <org_study_id>CR108690</org_study_id>
    <secondary_id>54135419TRD4006</secondary_id>
    <nct_id>NCT04476446</nct_id>
  </id_info>
  <brief_title>An Expanded Access Protocol for Esketamine Treatment in Participants With Treatment Resistant Depression (TRD) Who do Not Have Other Treatment Alternatives</brief_title>
  <official_title>An Open-Label Expanded Access Protocol for Esketamine Treatment of Subjects With Treatment Resistant Depression (TRD) Who do Not Have Other Treatment Alternatives</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen-Cilag, S.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen-Cilag, S.A.</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 purpose of this expanded access program (EAP) is to provide expanded access to esketamine&#xD;
      treatment and collect additional safety data and quality of life until esketamine is&#xD;
      commercially available for participants with Treatment-Resistant Depression (TRD).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 8, 2020</start_date>
  <completion_date type="Actual">June 16, 2023</completion_date>
  <primary_completion_date type="Actual">June 16, 2023</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>Number of Participants with Adverse Events (AEs)</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in European Quality of Life (EuroQol) Group, 5-Dimension, 5-Level (EQ 5D-5L)</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>The EQ-5D-5L is a standardized instrument used as a measure of health outcome, designed for self-completion by respondents. The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of the 5 dimensions is divided into 5 levels of perceived problems. Where Level 1: no problem, Level 2: slight problems, Level 3: moderate problems, Level 4: severe problems and Level 5: extreme problems).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Depression</condition>
  <arm_group>
    <arm_group_label>Intranasal Esketamine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Induction Phase: Participants will self-administer esketamine intranasally 56 milligram (mg) on Day 1 followed by 56 mg or 84 mg (as a flexible dose regimen) twice per week for 4 weeks. Participants greater than or equal to (&gt;=) 65 years old will start at a dose of 28 mg on Day 1. Maintenance Phase: Participants will self-administer esketamine 56 mg or 84 mg intranasally once per week from Week 5 to Week 9. Subsequently from Week 9, based on the investigator's clinical judgment, participants will self-administer esketamine 56 mg or 84 mg intranasally once or twice a week.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Esketamine</intervention_name>
    <description>Participants will receive esketamine at doses of either 56 mg or 84 mg intranasally once or twice a week based on the investigator's clinical judgment.</description>
    <arm_group_label>Intranasal Esketamine</arm_group_label>
    <other_name>JNJ-54135419</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant must have an unmet medical need to treat treatment-resistant depression&#xD;
             (TRD) with Esketamine Nasal Spray, an investigational compound, that has not been&#xD;
             approved the local health authority. This means no other treatment options are&#xD;
             available and the participant must be unable to participate in a clinical trial; for&#xD;
             example, because they do not fulfill the eligibility criteria of the protocol or there&#xD;
             are no trial sites within a reasonable distance of where they reside&#xD;
&#xD;
          -  Participant must not participate in a clinical trial or be concurrently treated with&#xD;
             an investigational drug when being treated with Esketamine Nasal Spray&#xD;
&#xD;
          -  Participants must have TRD with the diagnosis verified by a psychiatrist, and have&#xD;
             exhausted all other options including all alternative treatment options with marketed&#xD;
             therapies, specifically (a) Participants must meet the Diagnostic and Statistical&#xD;
             Manual of Mental Disorders (5th edition) (DSM)-5 diagnostic criteria for&#xD;
             single-episode major depressive episode (MDD) (if single-episode MDD, the duration&#xD;
             must be 2 years) or recurrent MDD, without psychotic features (b) Participants must&#xD;
             have had nonresponse to 2 or more oral antidepressant (of the same or a different&#xD;
             class) treatments in the current episode of depression confirmed by documented medical&#xD;
             history and/or pharmacy/prescription records i.e., treatments were prescribed in&#xD;
             adequate dosages for adequate duration with affirmation of treatment adherence, to&#xD;
             meet criteria for TRD, and have failed at least one augmentation/combination strategy&#xD;
             and have failed an adequate course (greater than or equal to [&gt;=] 7 sessions) of, or&#xD;
             have a contraindication/no access or refuses electro-convulsive therapy (ECT)&#xD;
&#xD;
          -  Participants must have exhausted clinical trials, early access programs or named&#xD;
             patient programs that may be available in your region&#xD;
&#xD;
          -  Participants must have moderate to severe depression per clinical judgement&#xD;
&#xD;
          -  Participants must be medically stable based on physical examination, medical history,&#xD;
             vital signs (including stable blood pressure) and 12-lead electrocardiogram (ECG)&#xD;
             performed prior to dosing&#xD;
&#xD;
          -  Participants must be medically stable based on clinical laboratory tests (complete&#xD;
             blood count (CBC), chemistry, liver enzymes and thyroid stimulating hormone [TSH])&#xD;
             performed prior to first dose&#xD;
&#xD;
          -  Participants must be comfortable with self-administration of intranasal medication and&#xD;
             be able to follow the intranasal administration instructions provided&#xD;
&#xD;
          -  Before the start of dosing, a woman must be either: non-childbirth potential or&#xD;
             practicing a highly effective method of birth control consistent with local&#xD;
             regulations. Men must agree to use a barrier method of birth control.&#xD;
&#xD;
          -  A woman of childbearing potential must have a negative serum (beta-human chorionic&#xD;
             gonadotropin [beta-hCG]) before dosing begins and a negative urine pregnancy test each&#xD;
             time tested&#xD;
&#xD;
          -  Participants must be willing and able to adhere to the prohibitions and restrictions&#xD;
             specified for study&#xD;
&#xD;
          -  Each participant must sign an informed consent form (ICF) indicating that he or she&#xD;
             understands the purpose of and procedures required for early access program (EPA) and&#xD;
             is willing to participate in the EPA, if required by law or regulation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The participant's depressive symptoms have previously demonstrated nonresponse to&#xD;
             Esketamine Nasal Spray or ketamine in the current major depressive episode per&#xD;
             clinical judgment&#xD;
&#xD;
          -  Participant has a current or prior Diagnostic and Statistical Manual of Mental&#xD;
             Disorders (DSM)-5 diagnosis of a psychotic disorder or major depressive episode (MDD)&#xD;
             with psychosis, bipolar or related disorders, or intellectual disability (only DSM-5&#xD;
             diagnostic code 319).&#xD;
&#xD;
          -  Participant has homicidal ideation/intent or has suicidal ideation with some intent to&#xD;
             act within 6 months per the requesting psychiatrist's clinical judgment&#xD;
&#xD;
          -  Participant has a history of moderate or severe substance or alcohol use disorder&#xD;
             according to DSM-5 criteria, except nicotine or caffeine, within 6 months before the&#xD;
             start of the first dose. (a). A history (lifetime) of ketamine, phencyclidine (PCP),&#xD;
             lysergic acid diethylamide (LSD), or 3, 4-methylenedioxy-methamphetamine (MDMA)&#xD;
             hallucinogen-related use disorder is exclusionary&#xD;
&#xD;
          -  Participants with active seizures (uncomplicated childhood febrile seizures with no&#xD;
             sequelae are not exclusionary). Participants with a history of seizure are allowed&#xD;
             provided that seizures are controlled, and no seizure has been experienced in the 6&#xD;
             months prior to expanded access protocol (EAP) entry&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen-Cilag, S.A. Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen-Cilag, S.A.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ketamine Mexico S. de RL. de C.V.</name>
      <address>
        <city>Cdmx</city>
        <zip>4100</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Espanol</name>
      <address>
        <city>Ciudad de Mexico</city>
        <zip>11520</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clínica de Ansiedad, Depresión y Estrés CADE, S. de R.L. de C.V.</name>
      <address>
        <city>Guadalajara</city>
        <zip>44520</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gabipros SC.</name>
      <address>
        <city>Mexico City</city>
        <zip>07000</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Avalon Vinculación Médica En Salud Mental</name>
      <address>
        <city>Mexico City</city>
        <zip>11000</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ángel Alberto Ruiz Chow</name>
      <address>
        <city>Mexico</city>
        <zip>01000</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Especialidades en Neuropsiquiatría de México S.C.</name>
      <address>
        <city>Mexico</city>
        <zip>11000</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clínica de Interdisciplinas Congnitivo Conductuales</name>
      <address>
        <city>Mexico</city>
        <zip>11950</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>July 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>September 13, 2023</last_update_submitted>
  <last_update_submitted_qc>September 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 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>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Treatment-Resistant</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Esketamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The data sharing policy of the Janssen Pharmaceutical Companies of Johnson &amp; Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu</ipd_description>
    <ipd_url>https://www.janssen.com/clinical-trials/transparency</ipd_url>
  </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/NCT04476446
org study id: CR108690
secondary id: 54135419TRD4006
nct id: NCT04476446
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this expanded access program (EAP) is to provide expanded access to esketamine
      treatment and collect additional safety data and quality of life until esketamine is
      commercially available for participants with Treatment-Resistant Depression (TRD).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants with Adverse Events (AEs)
time frame: Up to 6 months
description: An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
measure: Change from Baseline in European Quality of Life (EuroQol) Group, 5-Dimension, 5-Level (EQ 5D-5L)
time frame: Up to 6 months
description: The EQ-5D-5L is a standardized instrument used as a measure of health outcome, designed for self-completion by respondents. The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of the 5 dimensions is divided into 5 levels of perceived problems. Where Level 1: no problem, Level 2: slight problems, Level 3: moderate problems, Level 4: severe problems and Level 5: extreme problems).
arm group label: Intranasal Esketamine
arm group type: Experimental
description: Induction Phase: Participants will self-administer esketamine intranasally 56 milligram (mg) on Day 1 followed by 56 mg or 84 mg (as a flexible dose regimen) twice per week for 4 weeks. Participants greater than or equal to (>=) 65 years old will start at a dose of 28 mg on Day 1. Maintenance Phase: Participants will self-administer esketamine 56 mg or 84 mg intranasally once per week from Week 5 to Week 9. Subsequently from Week 9, based on the investigator's clinical judgment, participants will self-administer esketamine 56 mg or 84 mg intranasally once or twice a week.
intervention type: Drug
intervention name: Esketamine
description: Participants will receive esketamine at doses of either 56 mg or 84 mg intranasally once or twice a week based on the investigator's clinical judgment.
arm group label: Intranasal Esketamine
other name: JNJ-54135419
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Janssen-Cilag, S.A. Clinical Trial
role: Study Director
affiliation: Janssen-Cilag, S.A.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Mexico
responsible party type: Sponsor
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Treatment-Resistant
mesh term: Esketamine
sharing ipd: Yes
ipd description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
ipd url: https://www.janssen.com/clinical-trials/transparency