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/NCT05997602</url>
    </required_header>
    <id_info>
      <org_study_id>FCN-159-004</org_study_id>
      <nct_id>NCT05997602</nct_id>
    </id_info>
    <brief_title>To Evaluate the Efficacy, Safety, and PK Characteristics of FCN-159 in Pediatric Patients With Refractory/Recurrent LCH</brief_title>
    <official_title>A Multi-center, Open-label, Single Arm Phase 2 Study to Evaluate the Efficacy, Safety, and Pharmacokinetic Characteristics of FCN-159 in Pediatric Patients With Refractory/Recurrent Langerhans Cell Histiocytosis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a rare disease, single-arm, open-label,multi-center, non-randomized Phase 2 clinical&#xD;
        study to evaluate the efficacy, safety, and pharmacokinetic characteristics of FCN-159&#xD;
        monotherapy in pediatric patients with refractory/recurrent Langerhans cell histiocytosis&#xD;
        (LCH).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a rare disease, single-arm, open-label,multi-center, non-randomized Phase 2 clinical&#xD;
        study to evaluate the efficacy, safety, and pharmacokinetic characteristics of FCN-159&#xD;
        monotherapy in pediatric patients with refractory/recurrent Langerhans cell histiocytosis&#xD;
        (LCH). Approximately 56 pediatric patients will be enrolled in this study.The study included&#xD;
        screening period, treatment period and follow-up period. Subjects will receive FCN-159 5mg/m²&#xD;
        (NMT 8mg, the recommended oral dose for adults), orally, once daily, continuously for 28 days&#xD;
        per cycle. Subjects will be treated until disease progression (PD), intolerable toxicity,&#xD;
        withdrawal of consent, death, or other protocol-specified reasons. According to the PET&#xD;
        Response Criteria and Langerhans Cell Histiocytosis Evaluation and Treatment Guidelines,&#xD;
        tumor assessment will be performed until the subject withdrawal of consent, or death.&#xD;
        Efficacy evaluation will be performed by the investigator and the Independent Review&#xD;
        Committee (IRC), respectively.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 14, 2023</start_date>
    <completion_date type="Anticipated">July 14, 2026</completion_date>
    <primary_completion_date type="Anticipated">July 14, 2024</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>Objective Response Rate (ORR) Evaluated by Independent Review Committee (IRC) Based on PET Response Criteria (PRC)</measure>
      <time_frame>up to 24months</time_frame>
      <description>ORR Evaluated by Independent Review Committee (IRC) Based on PET Response Criteria (PRC) is defined as the percentage of participants who achieved a best overall response of CMR or PMR assessed by investigator .</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate (ORR) Evaluated by the Investigator Based on PET Response Criteria (PRC) and Langerhans Cell Histiocytosis Evaluation and Treatment Guidelines (Histiocyte Society, April 2009, hereinafter referred to as &quot;Guidelines&quot;)</measure>
      <time_frame>up to 24months</time_frame>
      <description>The ORR Evaluated by the Investigator Based on PRC is defined as the percentage of participants who achieved a best overall response of CMR or PMR.&#xD;
  The ORR Evaluated by the Investigator Based on &quot;Guidelines&quot; is defined as the percentage of participants who achieved confirmed NAD or AD-better.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease Control Rate (DCR) Evaluated by the Investigator Based on PET Response Criteria (PRC) and &quot;Guidelines&quot;.</measure>
      <time_frame>up to 24months</time_frame>
      <description>The DCR Evaluated by the Investigator based on PRC is defined as the percentage of participants who achieved a best overall response of CMR or PMR or SMD .&#xD;
  The DCR Evaluated by the Investigator Based on &quot;Guidelines&quot; is defined as the percentage of participants who achieved a confirmed NAD or AD-better or AD-stable.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical benefit rate (CBR) Evaluated by the Investigator Based on PRC and &quot;Guidelines&quot;.</measure>
      <time_frame>up to 24months</time_frame>
      <description>The CBR Evaluated by the Investigator based on PRC is defined as the percentage of participants who achieved a best overall response of CMR or PMR or SMD for a duration of ≥ 24 weeks.&#xD;
  The CBR Evaluated by the Investigator Based on &quot;Guidelines&quot; is defined as the percentage of participants who achieved confirmed NAD or AD-better or AD stable for a duration of ≥ 24 weeks.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to Response (TTR) Evaluated by the Investigator Based on PET Response Criteria (PRC) and &quot;Guidelines&quot;</measure>
      <time_frame>up to 24months</time_frame>
      <description>The TTR Evaluated by the Investigator based on PRC is defined as the time from the first documented achievement of CMR or PMR (whichever comes first).&#xD;
  The TTR Evaluated by the Investigator based on the &quot;Guidelines&quot; criteria is defined as the time from the first documented achievement of NAD or AD-better (whichever comes first).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>One-year Progressive Free Survival (PFS) Rate Evaluated by the Investigator Based on PET Response Criteria (PRC) and &quot;Guidelines&quot;</measure>
      <time_frame>up to 12months</time_frame>
      <description>The 1-year PFS Rate Evaluated by the Investigator based on PRC is defined as the percentage of participants who did not achieve the first documented occurrence of PMD or death (whichever comes first) within one year after first administration of the study drug.&#xD;
  The 1-year PFS Rate Evaluated by the Investigator based on &quot;Guidelines&quot; is defined as the percentage of participants who did not achieve the first documented occurrence of AD-progression or death (whichever comes first) within one year after first administration of the study drug.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progressive Free Survival (PFS) Evaluated by the Investigator Based on PET Response Criteria (PRC) and &quot;Guidelines&quot;</measure>
      <time_frame>up to 24months</time_frame>
      <description>The PFS Evaluated by the Investigator based on PRC is defined as the time from the first administration of the study drug to the first documented occurrence of PMD or death (whichever comes first).&#xD;
  The PFS Evaluated by the Investigator based on &quot;Guidelines&quot; is defined as the time from the first administration of the study drug to the first documented occurrence of AD-progression or death (whichever comes first).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS)</measure>
      <time_frame>up to 24months</time_frame>
      <description>The OS is defined as the time from the first administration of the study drug in patients to death from any cause. Data from the patient without events will be censored at the date the patient is last known to be alive</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>One-year Overall Survival (OS) Rate</measure>
      <time_frame>up to 12months</time_frame>
      <description>The 1year OS Rate is defined as as the percentage of participants who did not achieve death due to any cause within one year after first administration of the study drug.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Two-year Progressive Free Survival (PFS) rate Evaluated by the PRC and &quot;Guidelines&quot;</measure>
      <time_frame>up to 24months</time_frame>
      <description>The 2-year PFS Rate Evaluated by the Investigator based on PRC is defined as the percentage of participants who did not achieve the first documented occurrence of PMD or death (whichever comes first) within two year after first administration of the study drug.&#xD;
  The 2-year PFS Rate Evaluated by the Investigator based on &quot;Guidelines&quot; is defined as the percentage of participants who did not achieve the first documented occurrence of AD-progression or death (whichever comes first) within two year after first administration of the study drug.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Two-year Overall Survival (OS) Rate</measure>
      <time_frame>up to 24months</time_frame>
      <description>The 2 year OS Rate is defined as the percentage of participants who did not achieve death due to any cause within two year after first administration of the study drug.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Treatment-emergent adverse events (TEAEs)</measure>
      <time_frame>up to 24months</time_frame>
      <description>Type and frequency of treatment-emergent adverse events (TEAEs) with toxicity grades evaluated according to the National Cancer Institute-Common Toxicity Criteria Adverse Event (NCI-CTCAE) version 5.0.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma Concentration of FCN-159</measure>
      <time_frame>up to 24months</time_frame>
      <description>Evaluation of the pharmacokinetic characteristics of FCN-159</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">56</enrollment>
    <condition>Langerhans Cell Histiocytosis</condition>
    <condition>LCH</condition>
    <arm_group>
      <arm_group_label>FCN-159</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Experimental: FCN-159 Dosage form:tablet Specification: 1mg，4mg Dose: FCN-159 5mg/m² (Maximum dose does not exceed 8mg), orally, once daily</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>FCN-159</intervention_name>
      <description>5mg/m² (Maximum dose does not exceed 8mg, the recommended oral dose for adults), orally, once daily, continuously for 28 days per cycle.</description>
      <arm_group_label>FCN-159</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age 2-16 (inclusive)&#xD;
  &#xD;
            2. Patients with histologically confirmed Langerhans cell histiocytosis (LCH) diagnosed&#xD;
               by the central laboratory.&#xD;
  &#xD;
            3. Able to provide sufficient tumor tissue samples or peripheral blood samples for the&#xD;
               central laboratory to conduct biomarker testing as follows: including but not limited&#xD;
               to ERBB3, BRAF, ARAF, HRAS, KRAS, NRAS, MEK (MAP2K1 and MAP2K2), and other MEK&#xD;
               upstream genes.&#xD;
  &#xD;
            4. Patients who have received at least prior first-line systemic treatment, defined as&#xD;
               treatment including vinblastine (VBL) and glucocorticoids for at least 2 weeks. VBL&#xD;
               can be substituted with vincristine (VCR) or vindesine (VDS). Alternatively, patients&#xD;
               may be unable to tolerate chemotherapy due to severe chemotherapy toxicity. Inability&#xD;
               to tolerate chemotherapy is defined as one of the following: Severe liver impairment&#xD;
               (liver enzyme elevation ≥ 5 × upper limit of normal (ULN) and bilirubin elevation ≥&#xD;
               1.5 × ULN), severe neurotoxicity related to vinca alkaloids, chemotherapy-related&#xD;
               intracranial hypertension, or grade 4 bone marrow depression with severe infection&#xD;
               (sepsis, severe pneumonia, etc.) after chemotherapy.&#xD;
  &#xD;
            5. Refractory/relapsed LCH is defined as the presence of one of the following:&#xD;
  &#xD;
                 1. Failure of prior treatment, i.e., no regression in risk organs after at least 2&#xD;
                    weeks of systemic treatment, or overall evaluation of AD-progression or AD-mix;&#xD;
  &#xD;
                 2. Initial response of the disease to first or second-line systemic treatment is NAD&#xD;
                    or AD-better or AD-stable, followed by disease activity recurrence after&#xD;
                    maintenance therapy for more than 3 months. Second-line treatment includes&#xD;
                    cytarabine and/or cladribine.&#xD;
  &#xD;
                 3. Persistent mutated gene positive in plasma free DNA testing during prior&#xD;
                    treatment (confirmed by 2 consecutive tests) or retest positive after treatment&#xD;
                    discontinuation;&#xD;
  &#xD;
                 4. Lack of regression in the affected central nervous system (including the&#xD;
                    pituitary gland) after treatment;&#xD;
  &#xD;
                 5. Presence of bone marrow involvement and/or hemophagocytic lymphohistiocytosis&#xD;
                    (HLH);&#xD;
  &#xD;
            6. Presence of evaluable lesions based on PET response criteria (PRC).&#xD;
  &#xD;
            7. Patients who have to have recovered from all acute toxic effects of prior anti-tumor&#xD;
               therapy, and all relevant toxicities must be ≤ grade 1 (except for alopecia and&#xD;
               ototoxicity).&#xD;
  &#xD;
            8. Expected survival at least ≥ 3 months;&#xD;
  &#xD;
            9. Lansky (≤ 15 years old) and Karnofsky (≥ 16 years old) performance status scores&#xD;
               should be ≥ 50%, as shown in Appendix 4.&#xD;
  &#xD;
           10. Patients or their legal guardians must be able to understand and willingly sign a&#xD;
               written informed consent form.&#xD;
  &#xD;
           11. For women of childbearing potential, a serum human chorionic gonadotropin (HCG)&#xD;
               pregnancy test must be negative within 7 days before starting treatment.&#xD;
  &#xD;
           12. For female patients of childbearing potential: Patients should agree to use effective&#xD;
               contraception methods during the treatment period and for at least 90 days after the&#xD;
               last dose of study treatment, using dual barrier contraception methods such as&#xD;
               condoms, oral or injectable contraceptives, intra-uterine contraceptive devices, etc.&#xD;
               Male patients should agree to refrain from donating sperm for at least 90 days after&#xD;
               the last dose of study treatment.&#xD;
  &#xD;
           13. Adequate bone marrow function: Absolute neutrophil count ≥ 1.0×109/L, hemoglobin ≥&#xD;
               90g/L, and platelets ≥ 75×109/L without the use of blood transfusions, blood products,&#xD;
               or granulocyte colony-stimulating factors. Patients with hematocytopenia below these&#xD;
               thresholds due to the underlying disease may be considered for inclusion based on the&#xD;
               investigator's comprehensive judgment.&#xD;
  &#xD;
           14. Adequate hepatic and renal function: Serum total bilirubin ≤ 1.5 × the upper limit of&#xD;
               normal (ULN), or ≤ 5× ULN for patients with Gilbert's syndrome or liver involvement;&#xD;
               aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline&#xD;
               phosphatase (AKP) ≤ 2.5 × ULN, or ≤ 10 × ULN for patients with liver involvement;&#xD;
               albumin ≥ 3g/dL; and creatinine clearance or isotopic glomerular filtration rate (GFR)&#xD;
               ≥ 50ml/min/1.73m2 or serum creatinine based on age; hepatic and renal impairment&#xD;
               caused by the primary disease may be considered for inclusion based on the&#xD;
               investigator's comprehensive judgment.&#xD;
  &#xD;
           15. Coagulation: International normalized ratio (INR) and activated partial thromboplastin&#xD;
               time (APTT) ≤ 1.5 ULN.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patients who have received any of the following prior treatments:&#xD;
  &#xD;
                 1. Chemotherapy, targeted therapy, immunotherapy, biologic therapy, or herbal&#xD;
                    anti-tumor therapy for LCH within 4 weeks before the start of the study drug or &lt;&#xD;
                    5 half-lives (whichever is shorter).&#xD;
  &#xD;
                 2. Strong CYP3A4, CYP2C8, and CYP2C9 inhibitors or inducers within 14 days before&#xD;
                    the start of the study drug, except for topical skin application.&#xD;
  &#xD;
                 3. Gowth factors that promote platelet or white blood cell count or function within&#xD;
                    7 days before the start of the study drug.&#xD;
  &#xD;
                 4. Radiotherapy or major surgical treatment (including craniotomy, thoracotomy,&#xD;
                    laparotomy, open bone or joint surgery, etc.) within 4 weeks before the start of&#xD;
                    the study drug.&#xD;
  &#xD;
                 5. Participated in other interventional clinical trials within 4 weeks before the&#xD;
                    start of the study drug.&#xD;
  &#xD;
                 6. MEK 1/2 inhibitors (those who have received this treatment for a short period of&#xD;
                    ≤ 2 weeks may be included).&#xD;
  &#xD;
                 7. Anticoagulants within 7 days before the start of the study drug for patients with&#xD;
                    brain tumors (intracranial masses).&#xD;
  &#xD;
                 8. Prednisone treatment &lt; 0.5mg/kg/day (or equivalent dose of other corticosteroids)&#xD;
                    is allowed within one month before enrollment, but must be discontinued 14 days&#xD;
                    before the start of the study drug. Patients with brain lesions receiving&#xD;
                    corticosteroid therapy for brain edema must maintain a stable dose for 14 days&#xD;
                    before enrollment. Hormone replacement therapy is allowed for patients with&#xD;
                    hypopituitarism due to primary disease involvement of the pituitary.&#xD;
  &#xD;
            2. Patients with a history of other malignant tumors or concurrent other malignant tumors&#xD;
               (excluding cured non-melanoma skin basal cell carcinoma, ductal carcinoma in situ of&#xD;
               the breast, or cervical carcinoma in situ).&#xD;
  &#xD;
            3. Uncontrolled hypertension (with medication treatment): Blood pressure (BP) greater&#xD;
               than or equal to the 95th percentile for age, height, and sex, as described in&#xD;
               Appendix 6.&#xD;
  &#xD;
            4. Patients with dysphagia, active gastrointestinal disease, malabsorption syndrome, or&#xD;
               other conditions that may affect the absorption of the study drug.&#xD;
  &#xD;
            5. Prior or current history of retinal vein obstruction (RVO), retinal pigment epithelial&#xD;
               detachment (RPED), glaucoma, and other clinically significant abnormal ophthalmologic&#xD;
               examination results.&#xD;
  &#xD;
            6. Interstitial pneumonia, including clinically significant radiation pneumonitis.&#xD;
               Interstitial pneumonia caused by pulmonary involvement of the primary disease will be&#xD;
               excluded.&#xD;
  &#xD;
            7. Patients will be excluded if their cardiac function or comorbidities meet any of the&#xD;
               following criteria:&#xD;
  &#xD;
                 1. During the screening period, 12-lead electrocardiogram (ECG) measurements will be&#xD;
                    taken three times at the study center with a mean value calculated using the QTcF&#xD;
                    formula provided by the instrument; patients with a mean value of QTcF &gt; 470&#xD;
                    milliseconds or with risk factors for QTcF prolongation, such as uncorrected&#xD;
                    hypokalemia, congenital long QT syndrome, or receiving drugs known to prolong&#xD;
                    QTcF interval (mainly class Ia, Ic, and III antiarrhythmic drugs) will be&#xD;
                    excluded from the study. Drugs with the potential to prolong the QTcF interval&#xD;
                    are listed in Appendix 7.&#xD;
  &#xD;
                 2. New York Heart Association (NYHA) Class 2 congestive heart failure as shown in&#xD;
                    Appendix 5.&#xD;
  &#xD;
                 3. Clinically significant arrhythmias, including but not limited to complete left&#xD;
                    bundle branch block, and second-degree atrioventricular block.&#xD;
  &#xD;
                 4. Known presence of clinically significant coronary heart disease, cardiomyopathy,&#xD;
                    or severe valvular disease.&#xD;
  &#xD;
                 5. Echocardiography examination indicating left ventricular ejection fraction (LVEF)&#xD;
                    &lt; 50%.&#xD;
  &#xD;
            8. Patients with active bacterial, fungal, or viral infections, including active&#xD;
               hepatitis B (defined as positive hepatitis B surface antigen and hepatitis B virus DNA&#xD;
               &gt; 1000IU/ml or meeting the diagnostic criteria for active hepatitis B infection at the&#xD;
               study center) or hepatitis C (positive hepatitis C virus RNA), or human&#xD;
               immunodeficiency virus (HIV positive) infection.&#xD;
  &#xD;
            9. Patients with known allergies to the study drug, other MEK1/2 inhibitors, or their&#xD;
               excipients.&#xD;
  &#xD;
           10. Patients with known tumor tissue genetic testing that indicates the presence of MAP2K1&#xD;
               exon 3 deletions (del) or deletion-insertion type (delins/indels) mutations.&#xD;
  &#xD;
           11. The investigator considers clinically significant cases that will impede participation&#xD;
               in the study or prevent compliance with safety requirements.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>2 Years</minimum_age>
      <maximum_age>16 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Zhang Rui, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Beijing Children's Hospital,Captial Medical University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Zhang Rui, MD</last_name>
      <phone>18611106187</phone>
      <email>ruizh1973@126.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 8, 2023</study_first_submitted>
    <study_first_submitted_qc>August 15, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 18, 2023</study_first_posted>
    <last_update_submitted>August 15, 2023</last_update_submitted>
    <last_update_submitted_qc>August 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 18, 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>Histiocytosis, Langerhans-Cell</mesh_term>
      <mesh_term>Histiocytosis</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/NCT05997602
  org study id: FCN-159-004
  nct id: NCT05997602
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This is a rare disease, single-arm, open-label,multi-center, non-randomized Phase 2 clinical
        study to evaluate the efficacy, safety, and pharmacokinetic characteristics of FCN-159
        monotherapy in pediatric patients with refractory/recurrent Langerhans cell histiocytosis
        (LCH).
  This is a rare disease, single-arm, open-label,multi-center, non-randomized Phase 2 clinical
        study to evaluate the efficacy, safety, and pharmacokinetic characteristics of FCN-159
        monotherapy in pediatric patients with refractory/recurrent Langerhans cell histiocytosis
        (LCH). Approximately 56 pediatric patients will be enrolled in this study.The study included
        screening period, treatment period and follow-up period. Subjects will receive FCN-159 5mg/m²
        (NMT 8mg, the recommended oral dose for adults), orally, once daily, continuously for 28 days
        per cycle. Subjects will be treated until disease progression (PD), intolerable toxicity,
        withdrawal of consent, death, or other protocol-specified reasons. According to the PET
        Response Criteria and Langerhans Cell Histiocytosis Evaluation and Treatment Guidelines,
        tumor assessment will be performed until the subject withdrawal of consent, or death.
        Efficacy evaluation will be performed by the investigator and the Independent Review
        Committee (IRC), respectively.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Objective Response Rate (ORR) Evaluated by Independent Review Committee (IRC) Based on PET Response Criteria (PRC)
  time frame: up to 24months
  description: ORR Evaluated by Independent Review Committee (IRC) Based on PET Response Criteria (PRC) is defined as the percentage of participants who achieved a best overall response of CMR or PMR assessed by investigator .
  measure: Objective Response Rate (ORR) Evaluated by the Investigator Based on PET Response Criteria (PRC) and Langerhans Cell Histiocytosis Evaluation and Treatment Guidelines (Histiocyte Society, April 2009, hereinafter referred to as "Guidelines")
  time frame: up to 24months
  description: The ORR Evaluated by the Investigator Based on PRC is defined as the percentage of participants who achieved a best overall response of CMR or PMR.
  The ORR Evaluated by the Investigator Based on "Guidelines" is defined as the percentage of participants who achieved confirmed NAD or AD-better.
  measure: Disease Control Rate (DCR) Evaluated by the Investigator Based on PET Response Criteria (PRC) and "Guidelines".
  time frame: up to 24months
  description: The DCR Evaluated by the Investigator based on PRC is defined as the percentage of participants who achieved a best overall response of CMR or PMR or SMD .
  The DCR Evaluated by the Investigator Based on "Guidelines" is defined as the percentage of participants who achieved a confirmed NAD or AD-better or AD-stable.
  measure: Clinical benefit rate (CBR) Evaluated by the Investigator Based on PRC and "Guidelines".
  time frame: up to 24months
  description: The CBR Evaluated by the Investigator based on PRC is defined as the percentage of participants who achieved a best overall response of CMR or PMR or SMD for a duration of ≥ 24 weeks.
  The CBR Evaluated by the Investigator Based on "Guidelines" is defined as the percentage of participants who achieved confirmed NAD or AD-better or AD stable for a duration of ≥ 24 weeks.
  measure: Time to Response (TTR) Evaluated by the Investigator Based on PET Response Criteria (PRC) and "Guidelines"
  time frame: up to 24months
  description: The TTR Evaluated by the Investigator based on PRC is defined as the time from the first documented achievement of CMR or PMR (whichever comes first).
  The TTR Evaluated by the Investigator based on the "Guidelines" criteria is defined as the time from the first documented achievement of NAD or AD-better (whichever comes first).
  measure: One-year Progressive Free Survival (PFS) Rate Evaluated by the Investigator Based on PET Response Criteria (PRC) and "Guidelines"
  time frame: up to 12months
  description: The 1-year PFS Rate Evaluated by the Investigator based on PRC is defined as the percentage of participants who did not achieve the first documented occurrence of PMD or death (whichever comes first) within one year after first administration of the study drug.
  The 1-year PFS Rate Evaluated by the Investigator based on "Guidelines" is defined as the percentage of participants who did not achieve the first documented occurrence of AD-progression or death (whichever comes first) within one year after first administration of the study drug.
  measure: Progressive Free Survival (PFS) Evaluated by the Investigator Based on PET Response Criteria (PRC) and "Guidelines"
  time frame: up to 24months
  description: The PFS Evaluated by the Investigator based on PRC is defined as the time from the first administration of the study drug to the first documented occurrence of PMD or death (whichever comes first).
  The PFS Evaluated by the Investigator based on "Guidelines" is defined as the time from the first administration of the study drug to the first documented occurrence of AD-progression or death (whichever comes first).
  measure: Overall Survival (OS)
  time frame: up to 24months
  description: The OS is defined as the time from the first administration of the study drug in patients to death from any cause. Data from the patient without events will be censored at the date the patient is last known to be alive
  measure: One-year Overall Survival (OS) Rate
  time frame: up to 12months
  description: The 1year OS Rate is defined as as the percentage of participants who did not achieve death due to any cause within one year after first administration of the study drug.
  measure: Two-year Progressive Free Survival (PFS) rate Evaluated by the PRC and "Guidelines"
  time frame: up to 24months
  description: The 2-year PFS Rate Evaluated by the Investigator based on PRC is defined as the percentage of participants who did not achieve the first documented occurrence of PMD or death (whichever comes first) within two year after first administration of the study drug.
  The 2-year PFS Rate Evaluated by the Investigator based on "Guidelines" is defined as the percentage of participants who did not achieve the first documented occurrence of AD-progression or death (whichever comes first) within two year after first administration of the study drug.
  measure: Two-year Overall Survival (OS) Rate
  time frame: up to 24months
  description: The 2 year OS Rate is defined as the percentage of participants who did not achieve death due to any cause within two year after first administration of the study drug.
  measure: Treatment-emergent adverse events (TEAEs)
  time frame: up to 24months
  description: Type and frequency of treatment-emergent adverse events (TEAEs) with toxicity grades evaluated according to the National Cancer Institute-Common Toxicity Criteria Adverse Event (NCI-CTCAE) version 5.0.
  measure: Plasma Concentration of FCN-159
  time frame: up to 24months
  description: Evaluation of the pharmacokinetic characteristics of FCN-159
  arm group label: FCN-159
  arm group type: Experimental
  description: Experimental: FCN-159 Dosage form:tablet Specification: 1mg，4mg Dose: FCN-159 5mg/m² (Maximum dose does not exceed 8mg), orally, once daily
  intervention type: Drug
  intervention name: FCN-159
  description: 5mg/m² (Maximum dose does not exceed 8mg, the recommended oral dose for adults), orally, once daily, continuously for 28 days per cycle.
  arm group label: FCN-159
  criteria: 
  gender: All
  minimum age: 2 Years
  maximum age: 16 Years
  healthy volunteers: No
  last name: Zhang Rui, MD
  role: Principal Investigator
  affiliation: Beijing Children's Hospital,Captial Medical University
  last name: Zhang Rui, MD
  phone: 18611106187
  email: ruizh1973@126.com
  responsible party type: Sponsor
  mesh term: Histiocytosis, Langerhans-Cell
  mesh term: Histiocytosis