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/NCT06024265</url>
    </required_header>
    <id_info>
      <org_study_id>ER2001-001</org_study_id>
      <nct_id>NCT06024265</nct_id>
    </id_info>
    <brief_title>The Safety and Tolerability Study With ER2001 Intravenous Injection in Adults With Early Manifest Huntington's Disease</brief_title>
    <official_title>An Open-Label, Dose Escalation Early Phase 1 Study of ER2001 Intravenous Injection in Adults With Early Manifest Huntington's Disease</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>ExoRNA Bioscience</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>ExoRNA Bioscience</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>
        This is an open label, dose escalation clinic trial of ER2001 intravenous injection to&#xD;
        evaluate safety, tolerability and pharmacokinetics of ascending single and multiple doses of&#xD;
        intravenously administered ER2001 in patients with early manifest Huntington's Disease.&#xD;
        Furthermore, pharmacodynamics in particular target engagement, and early clinical signs of&#xD;
        efficacy will be assessed. This study will evaluate increasing doses of ER2001 in sequential&#xD;
        cohorts. ER2001 was escalated over 4 dose levels . The planned duration of this treatment is&#xD;
        14 weeks.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Participants will receive totally 8 intravenous injections of ER2001 on the first day of the&#xD;
        study, after 2 weeks they will receive 6 injections at weekly intervals, followed by 1&#xD;
        injections at 6 weeks interval. The treatment period of 14 weeks will be followed by an&#xD;
        observation phase of 84 days . A modified 3 plus 3 dose-escalation design will be employed&#xD;
        with escalating rules set according to the incidence of dose-limiting toxicity (DLT). The&#xD;
        first cohort of 1-6 participants will receive a low dose. After safety analysis the next&#xD;
        cohort of 3-6 will received a higher dose. Planned doses for increase in subsequent cohorts&#xD;
        are 0.04, 0.08, 0.16, and 0.32 mg/kg. Decision to proceed to the next higher dose cohort will&#xD;
        be based upon a safety review of the included participants. Treatment will continue until&#xD;
        intolerable toxicity or as per patient preference.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">April 4, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">October 4, 2024</primary_completion_date>
    <phase>Early Phase 1</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>
      <intervention_model_description>As designed, the single group will be divided into four cohorts. The first cohort of 1-6 participants will receive an initial dose, followed by a safety review of the included participants. If the safety is confirmed and decision made to proceed to the next higher dose, the next cohort of 3-6 participants will receive a higher dose. The planned increasing doses are 0.04, 0.08, 0.16, and 0.32 mg/kg, respectively in subsequent.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence and Severity of adverse events (AEs) and serious adverse events (SAEs)</measure>
      <time_frame>Approximately 6.5 months</time_frame>
      <description>To evaluate the safety and tolerability of ER2001 injection.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Peak Plasma Concentration (Cmax)</measure>
      <time_frame>Approximately 3.5 months</time_frame>
      <description>To assess the Pharmacokinetics (PK) of ER2001 injection.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Terminal half-life (t1/2)</measure>
      <time_frame>Approximately 3.5 months</time_frame>
      <description>To assess the Pharmacokinetics (PK) of ER2001 injection.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the plasma concentration versus time curve from time 0 to the last quantifiable concentration (AUC0-t)</measure>
      <time_frame>Approximately 3.5 months</time_frame>
      <description>To assess the Pharmacokinetics (PK) of ER2001 injection.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Maximum concentration (Cmax) in cerebrospinal fluid (CSF)</measure>
      <time_frame>Approximately 3.5 months</time_frame>
      <description>To assess the Pharmacokinetics (PK) of ER2001 injection.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Immunogenicity</measure>
      <time_frame>approximately- 6.5 months</time_frame>
      <description>To collect the incidence of Anti-Drug Antibodies (ADAs).</description>
    </other_outcome>
    <other_outcome>
      <measure>Change from baseline in the concentration of mutant huntingtin (mHTT) protein in cerebrospinal fluid (CSF)</measure>
      <time_frame>approximately- 6.5 months</time_frame>
      <description>To assess the dose-response relationship of ER2001 injection on mHTT protein change from baseline in cerebrospinal fluid (CSF).</description>
    </other_outcome>
    <other_outcome>
      <measure>Change from baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Functional Capacity (TFC) score</measure>
      <time_frame>approximately- 6.5 months</time_frame>
      <description>UHDRS is a research tool developed by Huntington Disease (HD) Study Group to provide a uniform assessment of the clinical features and course of HD. The UHDRS TFC comprises 5 functional domains associated with disability (occupation, finances, domestic chores, activities of daily living, and care level), with scores on each item ranging from 0 to either 2 or 3. The TFC total score is the sum of the 5 TFC items and can range from 0 to 13, with greater scores indicating higher functioning. Negative change from baseline indicates worsening.</description>
    </other_outcome>
    <other_outcome>
      <measure>Change from baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score (TMS) score</measure>
      <time_frame>approximately- 6.5 months</time_frame>
      <description>UHDRS is a research tool developed by Huntington Disease (HD) Study Group to provide a uniform assessment of the clinical features and course of HD. The UHDRS TMS assesses all the motor features of HD and includes maximal chorea, maximal dystonia, ocular pursuit, saccade initiation and velocity, dysarthria, tongue protrusion, finger tapping, hand pronation and supination, luria, rigidity, bradykinesia, gait, tandem walking, and retropulsion pull test. Each of these was rated on a scale of 0 (normal motor function) to 4 (severely impaired motor function). TMS score is a sum of individual scores ranging from 0 (normal motor function) to 124 (severely impaired motor function). Lower TMS scores indicate better motor function.</description>
    </other_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">15</enrollment>
    <condition>Huntington Disease</condition>
    <arm_group>
      <arm_group_label>ER2001 Injection</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The minimum initial dose is 0.04mg/kg, then escalate to 0.08mg/kg, 0.16mg/kg and 0.32mg/kg. The planned duration of the treatment is 14 weeks, and ER2001 will be administrated intravenously at the first day of weeks 1, 3, 4, 5, 6, 7, 8, and 14.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>ER2001 injection</intervention_name>
      <description>The minimum initial dose is 0.04mg/kg, then escalate to 0.08mg/kg, 0.16mg/kg and 0.32mg/kg. The planned duration of the treatment is 14 weeks, and ER2001 will be administrated intravenously at the first day of weeks 1, 3, 4, 5, 6, 7, 8, and 14.</description>
      <arm_group_label>ER2001 Injection</arm_group_label>
      <other_name>ER2001 intravenous injection solution</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patient has documented ability to understand the written study informed consent forms&#xD;
               (ICFs) at the time of screening and has provided signed written informed consent prior&#xD;
               to any study procedures.&#xD;
  &#xD;
            2. 25 Years to 55 Years. Gender is not limited.&#xD;
  &#xD;
            3. Early manifest HD as defined by a UHDRS total functional capacity (TFC) score of 9 to&#xD;
               13 and a diagnostic classification level (DCL) of 4.&#xD;
  &#xD;
            4. HTT gene expansion testing with the presence of ≥40 CAG repeats.&#xD;
  &#xD;
            5. Ability to undergo and tolerate MRI scans.&#xD;
  &#xD;
            6. Ability to undergo and tolerate lumbar puncture.&#xD;
  &#xD;
            7. All HD medications given for motor, behavioral, and cognitive symptoms have been&#xD;
               stable for 3 months prior to Screening.&#xD;
  &#xD;
            8. Other concomitant medications have been stable for 1 month prior to Screening.&#xD;
  &#xD;
            9. organ function measured prior to administration of study treatment.&#xD;
  &#xD;
           10. Postmenopausal or evidence of non-childbearing status for women of childbearing&#xD;
               potential. Male patients must use a condom during treatment and for 6 months after the&#xD;
               last dose of ER2001 when having sexual intercourse with a pregnant woman or with a&#xD;
               woman of childbearing potential. Female partners of male patients should also use a&#xD;
               highly effective form of contraception if they are of childbearing potential.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. History of attempted suicide or suicidal ideation with plan (i.e., active suicidal&#xD;
               ideation) that required hospital visit and/or change in level of care within 12 months&#xD;
               prior to screening.&#xD;
  &#xD;
            2. Current active psychosis, confusional state, or violent behavior.&#xD;
  &#xD;
            3. Bleeding tendency or history of coagulation disorder; As long as the investigator&#xD;
               confirms that there is no evidence of bleeding tendency or coagulation dysfunction at&#xD;
               present.&#xD;
  &#xD;
            4. ECG with corrected QT interval (QTc) &gt; 480 ms and/or indication of uncontrolled&#xD;
               cardiac conditions, as judged by the investigator (e.g. unstable ischemia,&#xD;
               uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial&#xD;
               infarction,congestive heart failure, electrolyte disturbances, etc.)&#xD;
  &#xD;
            5. Patients with HIV, Treponema pallidum, Hepatitis B, or Hepatitis C infection.&#xD;
  &#xD;
            6. Need to take antiretroviral drugs, including antiretroviral drugs as preventive&#xD;
               treatment.&#xD;
  &#xD;
            7. Current or recurrent disease, infection, or other significant concurrent medical&#xD;
               condition or medications that could confound clinical and laboratory evaluations or&#xD;
               could affect a subject's safety or their ability to undergo the neurosurgical&#xD;
               procedure or comply with the procedures and study visit schedule.&#xD;
  &#xD;
            8. Clinical diagnosis of chronic migraines.&#xD;
  &#xD;
            9. Presence of an implanted deep brain stimulation device, ventriculoperitoneal or other&#xD;
               CSF shunt, or other implanted catheter.&#xD;
  &#xD;
           10. Preexisting structural brain lesions (such as tumor, arteriovenous malformation) as&#xD;
               assessed by a centrally read MRI scan during the screening period.&#xD;
  &#xD;
           11. Any history of gene therapy, RNA or DNA investigational agents, such as antisense&#xD;
               oligonucleotides (ASO), cell transplantation or any other experimental brain surgery.&#xD;
  &#xD;
           12. Treatment with investigational therapy within 4 weeks prior to screening or 5 drug&#xD;
               elimination half-lives of investigational therapy, whichever is longer.&#xD;
  &#xD;
           13. Unable or unsafe to perform lumbar puncture on the patient.&#xD;
  &#xD;
           14. In the Investigator's judgment, that Parkinson's disease, multiple system atrophy and&#xD;
               other dystonia diseases may be combined.&#xD;
  &#xD;
           15. Patients who are hypersensitive to any ingredients in the formulation of ER2001.&#xD;
  &#xD;
           16. Malignancy within 5 years of screening, except for basal or squamous cell carcinoma of&#xD;
               the skin or carcinoma in situ of the cervix that has been successfully treated.&#xD;
  &#xD;
           17. Concurrent or planned concurrent participation in any interventional clinical study,&#xD;
               including explicit pharmacological and non-pharmacological interventions.&#xD;
               Observational studies are acceptable.&#xD;
  &#xD;
           18. Any serious medical condition or clinically significant laboratory, vital signs, or&#xD;
               abnormalities at screening that, in the Investigator's judgment, precludes the&#xD;
               patient's safe participation in and completion of the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>25 Years</minimum_age>
      <maximum_age>55 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Xia Meng, Ph.D</last_name>
      <role>Study Chair</role>
      <affiliation>ExoRNA Bioscience</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Li Lin, Ph.D</last_name>
      <phone>+86-13816957902</phone>
      <email>li.lin@exornabio.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>First Affiliated Hospital of Guangzhou Medical University</name>
        <address>
          <city>Guangzhou</city>
          <state>Guangdong</state>
          <zip>510080</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>xiang chen, Ph.D</last_name>
        <phone>+86-15602398386</phone>
        <email>wuliancx@163.com</email>
      </contact>
      <investigator>
        <last_name>pingyi xu, Ph.D</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <reference>
      <citation>Zhang L, Wu T, Shan Y, Li G, Ni X, Chen X, Hu X, Lin L, Li Y, Guan Y, Gao J, Chen D, Zhang Y, Pei Z, Chen X. Therapeutic reversal of Huntington's disease by in vivo self-assembled siRNAs. Brain. 2021 Dec 16;144(11):3421-3435. doi: 10.1093/brain/awab354.</citation>
      <PMID>34918046</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>May 25, 2023</study_first_submitted>
    <study_first_submitted_qc>August 29, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 6, 2023</study_first_posted>
    <last_update_submitted>August 29, 2023</last_update_submitted>
    <last_update_submitted_qc>August 29, 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>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Huntington Disease</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/NCT06024265
  org study id: ER2001-001
  nct id: NCT06024265
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This is an open label, dose escalation clinic trial of ER2001 intravenous injection to
        evaluate safety, tolerability and pharmacokinetics of ascending single and multiple doses of
        intravenously administered ER2001 in patients with early manifest Huntington's Disease.
        Furthermore, pharmacodynamics in particular target engagement, and early clinical signs of
        efficacy will be assessed. This study will evaluate increasing doses of ER2001 in sequential
        cohorts. ER2001 was escalated over 4 dose levels . The planned duration of this treatment is
        14 weeks.
  Participants will receive totally 8 intravenous injections of ER2001 on the first day of the
        study, after 2 weeks they will receive 6 injections at weekly intervals, followed by 1
        injections at 6 weeks interval. The treatment period of 14 weeks will be followed by an
        observation phase of 84 days . A modified 3 plus 3 dose-escalation design will be employed
        with escalating rules set according to the incidence of dose-limiting toxicity (DLT). The
        first cohort of 1-6 participants will receive a low dose. After safety analysis the next
        cohort of 3-6 will received a higher dose. Planned doses for increase in subsequent cohorts
        are 0.04, 0.08, 0.16, and 0.32 mg/kg. Decision to proceed to the next higher dose cohort will
        be based upon a safety review of the included participants. Treatment will continue until
        intolerable toxicity or as per patient preference.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: As designed, the single group will be divided into four cohorts. The first cohort of 1-6 participants will receive an initial dose, followed by a safety review of the included participants. If the safety is confirmed and decision made to proceed to the next higher dose, the next cohort of 3-6 participants will receive a higher dose. The planned increasing doses are 0.04, 0.08, 0.16, and 0.32 mg/kg, respectively in subsequent.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence and Severity of adverse events (AEs) and serious adverse events (SAEs)
  time frame: Approximately 6.5 months
  description: To evaluate the safety and tolerability of ER2001 injection.
  measure: Peak Plasma Concentration (Cmax)
  time frame: Approximately 3.5 months
  description: To assess the Pharmacokinetics (PK) of ER2001 injection.
  measure: Terminal half-life (t1/2)
  time frame: Approximately 3.5 months
  description: To assess the Pharmacokinetics (PK) of ER2001 injection.
  measure: Area under the plasma concentration versus time curve from time 0 to the last quantifiable concentration (AUC0-t)
  time frame: Approximately 3.5 months
  description: To assess the Pharmacokinetics (PK) of ER2001 injection.
  measure: Maximum concentration (Cmax) in cerebrospinal fluid (CSF)
  time frame: Approximately 3.5 months
  description: To assess the Pharmacokinetics (PK) of ER2001 injection.
  measure: Immunogenicity
  time frame: approximately- 6.5 months
  description: To collect the incidence of Anti-Drug Antibodies (ADAs).
  measure: Change from baseline in the concentration of mutant huntingtin (mHTT) protein in cerebrospinal fluid (CSF)
  time frame: approximately- 6.5 months
  description: To assess the dose-response relationship of ER2001 injection on mHTT protein change from baseline in cerebrospinal fluid (CSF).
  measure: Change from baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Functional Capacity (TFC) score
  time frame: approximately- 6.5 months
  description: UHDRS is a research tool developed by Huntington Disease (HD) Study Group to provide a uniform assessment of the clinical features and course of HD. The UHDRS TFC comprises 5 functional domains associated with disability (occupation, finances, domestic chores, activities of daily living, and care level), with scores on each item ranging from 0 to either 2 or 3. The TFC total score is the sum of the 5 TFC items and can range from 0 to 13, with greater scores indicating higher functioning. Negative change from baseline indicates worsening.
  measure: Change from baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score (TMS) score
  time frame: approximately- 6.5 months
  description: UHDRS is a research tool developed by Huntington Disease (HD) Study Group to provide a uniform assessment of the clinical features and course of HD. The UHDRS TMS assesses all the motor features of HD and includes maximal chorea, maximal dystonia, ocular pursuit, saccade initiation and velocity, dysarthria, tongue protrusion, finger tapping, hand pronation and supination, luria, rigidity, bradykinesia, gait, tandem walking, and retropulsion pull test. Each of these was rated on a scale of 0 (normal motor function) to 4 (severely impaired motor function). TMS score is a sum of individual scores ranging from 0 (normal motor function) to 124 (severely impaired motor function). Lower TMS scores indicate better motor function.
  arm group label: ER2001 Injection
  arm group type: Experimental
  description: The minimum initial dose is 0.04mg/kg, then escalate to 0.08mg/kg, 0.16mg/kg and 0.32mg/kg. The planned duration of the treatment is 14 weeks, and ER2001 will be administrated intravenously at the first day of weeks 1, 3, 4, 5, 6, 7, 8, and 14.
  intervention type: Drug
  intervention name: ER2001 injection
  description: The minimum initial dose is 0.04mg/kg, then escalate to 0.08mg/kg, 0.16mg/kg and 0.32mg/kg. The planned duration of the treatment is 14 weeks, and ER2001 will be administrated intravenously at the first day of weeks 1, 3, 4, 5, 6, 7, 8, and 14.
  arm group label: ER2001 Injection
  other name: ER2001 intravenous injection solution
  criteria: 
  gender: All
  minimum age: 25 Years
  maximum age: 55 Years
  healthy volunteers: No
  last name: Xia Meng, Ph.D
  role: Study Chair
  affiliation: ExoRNA Bioscience
  last name: Li Lin, Ph.D
  phone: +86-13816957902
  email: li.lin@exornabio.com
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  country: China
  citation: Zhang L, Wu T, Shan Y, Li G, Ni X, Chen X, Hu X, Lin L, Li Y, Guan Y, Gao J, Chen D, Zhang Y, Pei Z, Chen X. Therapeutic reversal of Huntington's disease by in vivo self-assembled siRNAs. Brain. 2021 Dec 16;144(11):3421-3435. doi: 10.1093/brain/awab354.
  PMID: 34918046
  responsible party type: Sponsor
  mesh term: Huntington Disease