<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/NCT03241784</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00013616</org_study_id>
    <nct_id>NCT03241784</nct_id>
  </id_info>
  <brief_title>T-Regulatory Cells in Amyotrophic Lateral Sclerosis</brief_title>
  <official_title>Expansion and Infusion of T-Regulatory Cells in Amyotrophic Lateral Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanley H. Appel, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Methodist Hospital Research Institute</source>
  <oversight_info>
    <has_dmc>No</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 an open-label pilot study to determine the safety and tolerability of infusions of&#xD;
      autologous CD4+ CD25+ regulatory T cells with concomitant subcutaneous IL-2 injections in 4&#xD;
      subjects with ALS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This Pilot Study will consist of 4 ALS subjects who will undergo 4 infusions of autologous&#xD;
      expanded Tregs with concomitant subcutaneous injections of IL-2 (2 x 105 IU/m2) 3 times&#xD;
      weekly for 52 weeks or at least until such time that interim analyses can confirm or negate&#xD;
      its benefit.&#xD;
&#xD;
      During the enrollment period up to four subjects will be recruited from patients known to our&#xD;
      clinic for screening, baseline measures and leukapheresis. The Treg cell manufacturing will&#xD;
      be performed in a GMP laboratory. The first subject will receive infusions of their expanded&#xD;
      Tregs (1x106 /kg) with concomitant subcutaneous IL-2 injections (2 x 105 IU/m2) 25 days (+/-&#xD;
      2 days) post leukapheresis. The 2nd subject will begin after the first subject has completed&#xD;
      the first 4 weeks and has experienced no untoward effects during this period. Once subjects&#xD;
      #1 and #2 have completed the first 4 weeks and no toxic events have occurred they will&#xD;
      therefore be considered safely past the first milestone and subject #3 will begin infusions.&#xD;
      After subject #3 has completed the first 4 weeks with no untoward effects, subject #4 may&#xD;
      begin infusions with the below modified schedule:&#xD;
&#xD;
      The 4th subject will undergo infusion of autologous expanded Tregs once every four weeks (+/-&#xD;
      2 days) for a total of four infusions, with concomitant subcutaneous injections of IL-2 (2 x&#xD;
      105 IU/m2) 3 times weekly. In addition, subject #4 will begin subcutaneous IL-2 injections 4&#xD;
      weeks before his first autologous Treg infusion. An additional office visit will take place 2&#xD;
      weeks after initiating IL-2 for clinical evaluation, scoring and blood draw. Office visits&#xD;
      will then be completed every two weeks while the subject is receiving Treg infusions for&#xD;
      clinical evaluation, scoring, and blood draws. Then, the subject will be seen in office&#xD;
      visits once per month for one year total for clinical evaluation, scoring, and blood draws.&#xD;
&#xD;
      In addition, subjects #1, 2 and 3 will repeat the leukapheresis (under a separate protocol)&#xD;
      and undergo Treg infusions at the modified schedule of every 4 weeks, with concomitant&#xD;
      subcutaneous injections of IL-2 (2 x 105 IU/m2) 3 times weekly. The subjects will be called&#xD;
      on Day 7, and 21. Office visits will be completed on the day after infusions and every two&#xD;
      weeks while the subjects are undergoing Treg infusions for clinical evaluation, scoring, and&#xD;
      blood draws. The subjects will then be seen during office visits once per month for one year&#xD;
      total from their initial baseline visit for clinical evaluation, scoring, and blood draws&#xD;
&#xD;
      Monthly interim analyses will monitor the subjects using validated ALS scales such as the&#xD;
      ALSFRS-R and Appel Scale, which incorporates muscle strength and dysfunction, activities of&#xD;
      daily living and pulmonary function. The analyses will also include interim medical history&#xD;
      and physical exam, EKG when indicated, safety labs (such as CBC, chemistry, liver function,&#xD;
      T4 and TSH) as well as more technical research labs such as T Regulatory Cell, Th1 and Th17&#xD;
      counts, FoxP3 RNA expression, and Treg Suppression Assays. A PT/PTT will be performed only if&#xD;
      the subject has an abnormal coagulation result at baseline or if the subject is on&#xD;
      anti-coagulation therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">May 16, 2016</start_date>
  <completion_date type="Anticipated">March 2018</completion_date>
  <primary_completion_date type="Actual">February 2018</primary_completion_date>
  <phase>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>Autologous infusion of expanded T-regulatory lymphocytes during early and late phases of ALS disease in patients with varying rates of disease progression.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>Baseline to two years</time_frame>
    <description>Clinical laboratory blood tests are standard to assure safety in clinical trials. Complete blood count, chemistry, liver function, throxine (T4) and thyroid stimulating hormone (TSH) will be assessed for normal reference ranges and abnormal (not clinically significant) results. Clinically abnormal results will be documented as adverse events as per CTCAE v4.0.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AALS (Appel ALS) Scale</measure>
    <time_frame>Baseline to week 15</time_frame>
    <description>The AALS is a published, validated instrument that consists of five sub-scores: bulbar, respiratory, muscle strength, and lower extremity and upper extremity function. Each group is composed of individual tests. The total Appel ALS score is 30 for healthy subjects and 164 for those with maximum impairment. The rate of change in the Appel ALS Rating Scale is a significant predictor of survival for subjects with ALS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ALSFRS-R (ALS Functional Rating Scale-Revised)</measure>
    <time_frame>Baseline to week 15</time_frame>
    <description>The ALSFRS-r (ALS Functional Rating Scale-revised) is an orally administered validated instrument using an ordinal rating scale used to determine the subject's assessment of their capability and independence in 12 functional activities. The scale addresses fine motor, gross motor, bulbar and respiratory function. The ALSFRS-r is used as a clinical assessment in ALS standard of care and in most ALS clinical trials.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T-Regulatory Cells</measure>
    <time_frame>Baseline to 3 months post treatment for a total of two years from baseline</time_frame>
    <description>Treg percentage (CD4+CD25+FOXP3+ cells) within the total CD4+ population will be assessed by multicolor flow cytometry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treg Suppression</measure>
    <time_frame>Baseline to 3 months post treatment for a total of two years from baseline</time_frame>
    <description>Treg suppressive function of T-effector (Teff) cells will be assessed by [3H]-thymidine incorporation. Correlation between changes in the rate of disease progression and the Treg percentage and function will be determined by Spearman's correlation analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TH17 and Th1 lymphocytes</measure>
    <time_frame>Baseline to 3 months post-treatment for a total of two years from baseline</time_frame>
    <description>The percentage of Tregs, Th1 lymphocytes and Th17 lymphocytes will be assessed by multicolor flow cytometry.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Pulmonary FVC - Exploratory Measure</measure>
    <time_frame>Baseline to 3 months post-treatment for a total of two years from baseline</time_frame>
    <description>FVC (Forced Vital Capacity). Reduction of pulmonary function is the primary source of morbidity and mortality in ALS. FVC testing will be used to monitor respiratory function. FVC measures the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.</description>
  </other_outcome>
  <other_outcome>
    <measure>Pulmonary MIP - Exploratory Measure</measure>
    <time_frame>Baseline to 3 months post-treatment for a total of two years from baseline</time_frame>
    <description>MIP (Maximum Inspiratory Pressure. Reduction of pulmonary function is the primary source of morbidity and mortality in ALS. MIP testing will be used to monitor respiratory function. MIP measures inspiratory muscle strength.</description>
  </other_outcome>
  <other_outcome>
    <measure>Tracheostomy- Exploratory Measure</measure>
    <time_frame>Baseline to 3 months post-treatment for a total of two years from baseline</time_frame>
    <description>Duration of tracheostomy-free survival</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">4</enrollment>
  <condition>ALS (Amyotrophic Lateral Sclerosis)</condition>
  <arm_group>
    <arm_group_label>Treatment arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects are enrolled in the one arm consisting of infusions of autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth/kg and subcutaneous injections of Interleukin-2 at a dose of 2x10 to the fifth IU/m2 three times a week.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Autologous T-regulatory lymphocytes</intervention_name>
    <description>intravenous administration of Autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth /kg.</description>
    <arm_group_label>Treatment arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Interleukin-2</intervention_name>
    <description>Subcutaneous Interleukin-2 at a dose of 2x10 to the fifth IU/m2, three times a week.</description>
    <arm_group_label>Treatment arm</arm_group_label>
    <other_name>IL-2</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18 years or older.&#xD;
&#xD;
          2. Sporadic or familial ALS diagnosed as possible, laboratory-supported probable,&#xD;
             probable, or definite as defined by revised El Escorial criteria (Appendix 1).&#xD;
&#xD;
          3. Subjects must not have taken riluzole for at least 30 days, or be on a stable dose of&#xD;
             riluzole for at least 30 days (riluzole-naïve subjects are permitted in the study).&#xD;
&#xD;
          4. Capable of providing informed consent and following trial procedures.&#xD;
&#xD;
          5. Geographically accessible to the site.&#xD;
&#xD;
          6. Women must not be able to become pregnant (e.g. post-menopausal, surgically sterile,&#xD;
             or using adequate birth control methods) for the duration of the study and three&#xD;
             months after study completion. Adequate contraception includes: abstinence, hormonal&#xD;
             contraception (oral contraception, implanted contraception, injected contraception or&#xD;
             other hormonal (patch or contraceptive ring, for example) contraception), intrauterine&#xD;
             device (IUD) in place for ≥ 3 months, barrier method in conjunction with spermicide,&#xD;
             or another adequate method.&#xD;
&#xD;
          7. Subjects must agree not to take live attenuated vaccines (including seasonal flu&#xD;
             vaccine) 30 days before blood collection.&#xD;
&#xD;
          8. Available autologous Tregs product with greater than or equal to 50% expression of&#xD;
             CD4, CD25 and FoxP3 determined by flow-cytometry.&#xD;
&#xD;
          9. Subjects must have been previously evaluated and followed clinically by a&#xD;
             neuromuscular specialist at Houston Methodist Neurological Institute&#xD;
&#xD;
         10. Normal Alanine aminotransferase level (ALT)&#xD;
&#xD;
         11. Normal Serum creatinine level&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior use of cells therapies&#xD;
&#xD;
          2. Concurrent use of other experimental ALS therapies&#xD;
&#xD;
          3. Pregnant or breastfeeding or planning to become pregnant or planning a partner's&#xD;
             pregnancy.&#xD;
&#xD;
          4. Other unstable medical or psychiatric illness&#xD;
&#xD;
          5. Known immune deficiency or history of lymphoma or leukemia&#xD;
&#xD;
          6. History of lymphopenia.&#xD;
&#xD;
          7. History of acquired or inherited immune deficiency syndrome, including leukopenia.&#xD;
&#xD;
          8. History of severe untreated chronic obstructive sleep apnea.&#xD;
&#xD;
          9. FVC less than 50% predicted at screening.&#xD;
&#xD;
         10. Exposure to any other agent currently under investigation for the treatment of&#xD;
             subjects with ALS (off-label use or investigational) within 30 days of the Baseline&#xD;
             Visit.&#xD;
&#xD;
         11. The presence of unstable psychiatric disease, cognitive impairment, or dementia that&#xD;
             would impair ability of the subject to provide informed consent, according to the PI's&#xD;
             judgment, or a history of active substance abuse within the prior year.&#xD;
&#xD;
         12. Clinically significant history of cardiac, oncologic, hepatic, or renal dysfunction,&#xD;
             or other medically significant illness.&#xD;
&#xD;
         13. The presence of any immunologic or autoimmune disease&#xD;
&#xD;
         14. Severe cardiac dysfunction defined clinically, or as a left ventricular ejection&#xD;
             fraction less than 40% of predicted or abnormal EKG findings.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stanley H Appel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Houston Methodist Neurological Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Methodist Neurological Institute</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>July 27, 2017</study_first_submitted>
  <study_first_submitted_qc>August 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <last_update_submitted>March 23, 2018</last_update_submitted>
  <last_update_submitted_qc>March 23, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>The Methodist Hospital Research Institute</investigator_affiliation>
    <investigator_full_name>Stanley H. Appel, MD</investigator_full_name>
    <investigator_title>TMHPO Chairman &amp; Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>ALS</keyword>
  <keyword>T-Regulatory Cells</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Motor Neuron Disease</mesh_term>
    <mesh_term>Amyotrophic Lateral Sclerosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Interleukin-2</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>November 1, 2019</submitted>
    <returned>November 20, 2019</returned>
    <submitted>April 9, 2021</submitted>
    <returned>May 4, 2021</returned>
  </pending_results>
  <!-- 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/NCT03241784
org study id: Pro00013616
nct id: NCT03241784
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is an open-label pilot study to determine the safety and tolerability of infusions of
      autologous CD4+ CD25+ regulatory T cells with concomitant subcutaneous IL-2 injections in 4
      subjects with ALS.
This Pilot Study will consist of 4 ALS subjects who will undergo 4 infusions of autologous
      expanded Tregs with concomitant subcutaneous injections of IL-2 (2 x 105 IU/m2) 3 times
      weekly for 52 weeks or at least until such time that interim analyses can confirm or negate
      its benefit.

      During the enrollment period up to four subjects will be recruited from patients known to our
      clinic for screening, baseline measures and leukapheresis. The Treg cell manufacturing will
      be performed in a GMP laboratory. The first subject will receive infusions of their expanded
      Tregs (1x106 /kg) with concomitant subcutaneous IL-2 injections (2 x 105 IU/m2) 25 days (+/-
      2 days) post leukapheresis. The 2nd subject will begin after the first subject has completed
      the first 4 weeks and has experienced no untoward effects during this period. Once subjects
      #1 and #2 have completed the first 4 weeks and no toxic events have occurred they will
      therefore be considered safely past the first milestone and subject #3 will begin infusions.
      After subject #3 has completed the first 4 weeks with no untoward effects, subject #4 may
      begin infusions with the below modified schedule:

      The 4th subject will undergo infusion of autologous expanded Tregs once every four weeks (+/-
      2 days) for a total of four infusions, with concomitant subcutaneous injections of IL-2 (2 x
      105 IU/m2) 3 times weekly. In addition, subject #4 will begin subcutaneous IL-2 injections 4
      weeks before his first autologous Treg infusion. An additional office visit will take place 2
      weeks after initiating IL-2 for clinical evaluation, scoring and blood draw. Office visits
      will then be completed every two weeks while the subject is receiving Treg infusions for
      clinical evaluation, scoring, and blood draws. Then, the subject will be seen in office
      visits once per month for one year total for clinical evaluation, scoring, and blood draws.

      In addition, subjects #1, 2 and 3 will repeat the leukapheresis (under a separate protocol)
      and undergo Treg infusions at the modified schedule of every 4 weeks, with concomitant
      subcutaneous injections of IL-2 (2 x 105 IU/m2) 3 times weekly. The subjects will be called
      on Day 7, and 21. Office visits will be completed on the day after infusions and every two
      weeks while the subjects are undergoing Treg infusions for clinical evaluation, scoring, and
      blood draws. The subjects will then be seen during office visits once per month for one year
      total from their initial baseline visit for clinical evaluation, scoring, and blood draws

      Monthly interim analyses will monitor the subjects using validated ALS scales such as the
      ALSFRS-R and Appel Scale, which incorporates muscle strength and dysfunction, activities of
      daily living and pulmonary function. The analyses will also include interim medical history
      and physical exam, EKG when indicated, safety labs (such as CBC, chemistry, liver function,
      T4 and TSH) as well as more technical research labs such as T Regulatory Cell, Th1 and Th17
      counts, FoxP3 RNA expression, and Treg Suppression Assays. A PT/PTT will be performed only if
      the subject has an abnormal coagulation result at baseline or if the subject is on
      anti-coagulation therapy.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Autologous infusion of expanded T-regulatory lymphocytes during early and late phases of ALS disease in patients with varying rates of disease progression.
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: Baseline to two years
description: Clinical laboratory blood tests are standard to assure safety in clinical trials. Complete blood count, chemistry, liver function, throxine (T4) and thyroid stimulating hormone (TSH) will be assessed for normal reference ranges and abnormal (not clinically significant) results. Clinically abnormal results will be documented as adverse events as per CTCAE v4.0.
measure: AALS (Appel ALS) Scale
time frame: Baseline to week 15
description: The AALS is a published, validated instrument that consists of five sub-scores: bulbar, respiratory, muscle strength, and lower extremity and upper extremity function. Each group is composed of individual tests. The total Appel ALS score is 30 for healthy subjects and 164 for those with maximum impairment. The rate of change in the Appel ALS Rating Scale is a significant predictor of survival for subjects with ALS.
measure: ALSFRS-R (ALS Functional Rating Scale-Revised)
time frame: Baseline to week 15
description: The ALSFRS-r (ALS Functional Rating Scale-revised) is an orally administered validated instrument using an ordinal rating scale used to determine the subject's assessment of their capability and independence in 12 functional activities. The scale addresses fine motor, gross motor, bulbar and respiratory function. The ALSFRS-r is used as a clinical assessment in ALS standard of care and in most ALS clinical trials.
measure: T-Regulatory Cells
time frame: Baseline to 3 months post treatment for a total of two years from baseline
description: Treg percentage (CD4+CD25+FOXP3+ cells) within the total CD4+ population will be assessed by multicolor flow cytometry.
measure: Treg Suppression
time frame: Baseline to 3 months post treatment for a total of two years from baseline
description: Treg suppressive function of T-effector (Teff) cells will be assessed by [3H]-thymidine incorporation. Correlation between changes in the rate of disease progression and the Treg percentage and function will be determined by Spearman's correlation analysis.
measure: TH17 and Th1 lymphocytes
time frame: Baseline to 3 months post-treatment for a total of two years from baseline
description: The percentage of Tregs, Th1 lymphocytes and Th17 lymphocytes will be assessed by multicolor flow cytometry.
measure: Pulmonary FVC - Exploratory Measure
time frame: Baseline to 3 months post-treatment for a total of two years from baseline
description: FVC (Forced Vital Capacity). Reduction of pulmonary function is the primary source of morbidity and mortality in ALS. FVC testing will be used to monitor respiratory function. FVC measures the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.
measure: Pulmonary MIP - Exploratory Measure
time frame: Baseline to 3 months post-treatment for a total of two years from baseline
description: MIP (Maximum Inspiratory Pressure. Reduction of pulmonary function is the primary source of morbidity and mortality in ALS. MIP testing will be used to monitor respiratory function. MIP measures inspiratory muscle strength.
measure: Tracheostomy- Exploratory Measure
time frame: Baseline to 3 months post-treatment for a total of two years from baseline
description: Duration of tracheostomy-free survival
arm group label: Treatment arm
arm group type: Experimental
description: All subjects are enrolled in the one arm consisting of infusions of autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth/kg and subcutaneous injections of Interleukin-2 at a dose of 2x10 to the fifth IU/m2 three times a week.
intervention type: Biological
intervention name: Autologous T-regulatory lymphocytes
description: intravenous administration of Autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth /kg.
arm group label: Treatment arm
intervention type: Biological
intervention name: Interleukin-2
description: Subcutaneous Interleukin-2 at a dose of 2x10 to the fifth IU/m2, three times a week.
arm group label: Treatment arm
other name: IL-2
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Stanley H Appel, MD
role: Principal Investigator
affiliation: Houston Methodist Neurological Institute
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: The Methodist Hospital Research Institute
investigator full name: Stanley H. Appel, MD
investigator title: TMHPO Chairman & Principal Investigator
mesh term: Motor Neuron Disease
mesh term: Amyotrophic Lateral Sclerosis
mesh term: Sclerosis
mesh term: Interleukin-2
sharing ipd: No
submitted: November 1, 2019
returned: November 20, 2019
submitted: April 9, 2021
returned: May 4, 2021