<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/NCT03829826</url>
  </required_header>
  <id_info>
    <org_study_id>18P.420</org_study_id>
    <nct_id>NCT03829826</nct_id>
  </id_info>
  <brief_title>Efficacy and Mechanism of Action of SCIg in Patients With Stiff Person Syndrome (SPS)</brief_title>
  <official_title>Efficacy and Mechanism of Action of SCIg in Patients With Stiff Person Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Thomas Jefferson University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Thomas Jefferson University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pilot, proof-of concept investigator-initiated trial planned for 22 patients with&#xD;
      the diagnosis of Stiff Person Syndrome (SPS). The study will compare efficacy of treatment&#xD;
      using subcutaneous immunoglobulin therapy (SCIg) compared to intravenous immunoglobulin&#xD;
      (IVIg) therapy. The majority of IVIg naïve subjects (those not already receiving IVIg) are&#xD;
      typically managed with non-immunotherapy mostly Gamma Aminobutyric Acid (GABA) -enhancing&#xD;
      drugs such as Baclofen or Diazepam.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Design:This is a proof of concept observational prospective, open label, study on the&#xD;
      safety, efficacy and convenience of treatment with SCIg study of 22 patients at Thomas&#xD;
      Jefferson University Hospital. Two cohorts of patients within the total of 22 will be&#xD;
      included; half of them (11 patients) currently receiving and responding to IVIg and the other&#xD;
      half starting de novo on SCIg. Patients diagnosed with SPS according to defined sets of&#xD;
      symptoms will be eligible to enroll.&#xD;
&#xD;
      The primary clinical outcome will be based on clinical efficacy measures, as used before for&#xD;
      the IVIg trial, based on changes in the Stiffness Index and Heightened Sensitivity scores,&#xD;
      using the validated scales that the investigators have had previously utilized and validated&#xD;
      (Dalakas et al 2001; see attached at the end of the protocol). These same measurements will&#xD;
      be applied while on IVIg (weeks 0, 4, 8, 12) and will be compared to the measurements&#xD;
      obtained during SCIg (weeks 16, 20, 24, 28). The secondary outcome will be Quality of Life&#xD;
      (QoL) responses and patient preference for each treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">June 2019</start_date>
  <completion_date type="Anticipated">May 2020</completion_date>
  <primary_completion_date type="Anticipated">February 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>A &gt;50% change from baseline on the Stiffness Index scores ( scale from 0-6; each item adds one) after 12 weeks of treatment.</measure>
    <time_frame>24 MONTHS</time_frame>
    <description>Proving that SCIg is as effective as IVIg on this clinical measure will be important for the patients who may have another treatment option avoiding the systemic side effects of IVIg</description>
  </primary_outcome>
  <primary_outcome>
    <measure>A &gt;50% change from baseline on the Heightened Sensitivity scores (scales from 1-7, each item adds one) after 12 weeks of treatment.</measure>
    <time_frame>24 months</time_frame>
    <description>Proving that SCIg is as effective as IVIg on this clinical measure will be important for the patients who may have another treatment option avoiding the systemic side effects of IVIg</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>A meaningful change on Quality of Life (QoL) measures after 12 weeks of SCIg based on 6 sets of QoL Questionnaires (mobility, self-care, usual activities, pain, anxiety/depression, health state)</measure>
    <time_frame>24 MONTHS</time_frame>
    <description>Proving that SCIg affects Quality of life, as IVIg does, will be important for the patients who may have another treatment option avoiding the systemic side effects of IVIg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>If SCIg reduces the anti-GAD antibody titers measured in the patient's blood samples by more than 30%</measure>
    <time_frame>24 MONTHS</time_frame>
    <description>An effect on the circulating anti-Glutamic Acid Decarboxylase (GAD) antibodies will elucidate the mechanism of action of SCIg and any correlation between efficacy and antibody titers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>If &gt;50% of patients prefer either SCIg or IVIg after 12 weeks of treatment based on a YES/NO questionnaire .</measure>
    <time_frame>24 MONTHS</time_frame>
    <description>Proving patients' preference is important because SCIg is self-administered at home and more convenient, without the need for hospitalizations.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">22</enrollment>
  <condition>Stiff-Person Syndrome</condition>
  <arm_group>
    <arm_group_label>Patients receiving IVIg</arm_group_label>
    <description>Patients are currently receiving IVIg regularly for at least every 6 weeks and exhibit a favorable response will be recruited into the study (11 patients). They will be observed for 12 weeks under their existing IVIg regimen and will undergo measurements of their impairment using the previously validated Stiffness and Sensitivity scales and quality of life questionnaire (QoL) at weeks 0, 4, 8, 12. At week 12, prior to the first SCIg infusion, blood will be drawn for humoral (immunological) studies. One week following the last dose of IVIg (at week 13), the participants will be started on SCIg at a total dose equivalent to the monthly dose of IVIg they have been receiving.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>de novo SCIg patients/IVIg-Naive Group</arm_group_label>
    <description>This other arm of the trial will include 11 patients naïve to IVIg who do not receive other immunotherapies while being symptomatic. These patients after a 12-week observation period will start directly on SCIg drug (HYQVIA), following the same schedule as described above for the previous group.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>HyQvia</intervention_name>
    <description>Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase</description>
    <arm_group_label>Patients receiving IVIg</arm_group_label>
    <arm_group_label>de novo SCIg patients/IVIg-Naive Group</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood drawn for humoral (immunological) studies.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Yes No Individuals with impaired decision-making capacity X Women of reproductive potential&#xD;
        X Pregnant women/fetuses/neonates X Men of reproductive potential X Minorities X Prisoners&#xD;
        X Economically or educationally disadvantaged persons X Students/employees X&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men or women aged &gt;18 years&#xD;
&#xD;
          -  Diagnosis of SPS based on standard criteria&#xD;
&#xD;
          -  IVIg Group: Receiving the equivalent of 1-2 g/kg IVIg every 4 weeks with dependence*&#xD;
             on IVIg to maintain clinical response *Dependence is clinically determined either by&#xD;
             symptomatic worsening of condition at the end of the inter-dose interval or by&#xD;
             worsening after dose reduction or discontinuation within the previous 3 months.&#xD;
&#xD;
          -  IVIg-Naïve Group: Patients with symptomatic SPS and never treated with IVIg&#xD;
             (IVIg-naïve group), poorly controlled with standard therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy, planned pregnancy, breast-feeding or unwillingness to practice&#xD;
             contraception&#xD;
&#xD;
          -  Severe concurrent medical conditions, which would prevent treatment or assessment,&#xD;
             including significant hematological, renal or liver dysfunction or malignancies&#xD;
&#xD;
          -  Initiation of immunomodulatory treatment other than IVIg in the past 3 months&#xD;
&#xD;
          -  Participation in a trial of an investigational medicinal product in the past 12 weeks&#xD;
&#xD;
          -  Presence of any medical condition, which in the opinion of the investigator might&#xD;
             interfere with performance or interpretation of this study.&#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_contact>
    <last_name>Marinos C Dalakas, MD</last_name>
    <phone>2159557865</phone>
    <email>marinos.dalakas@jefferson.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Vikram Puvenna</last_name>
    <phone>2159554672</phone>
    <email>vikram.puvenna@jefferson.edu</email>
  </overall_contact_backup>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>May 13, 2019</last_update_submitted>
  <last_update_submitted_qc>May 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 14, 2019</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>Stiff-Person Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <!-- 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/NCT03829826
org study id: 18P.420
nct id: NCT03829826
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a pilot, proof-of concept investigator-initiated trial planned for 22 patients with
      the diagnosis of Stiff Person Syndrome (SPS). The study will compare efficacy of treatment
      using subcutaneous immunoglobulin therapy (SCIg) compared to intravenous immunoglobulin
      (IVIg) therapy. The majority of IVIg naïve subjects (those not already receiving IVIg) are
      typically managed with non-immunotherapy mostly Gamma Aminobutyric Acid (GABA) -enhancing
      drugs such as Baclofen or Diazepam.
Study Design:This is a proof of concept observational prospective, open label, study on the
      safety, efficacy and convenience of treatment with SCIg study of 22 patients at Thomas
      Jefferson University Hospital. Two cohorts of patients within the total of 22 will be
      included; half of them (11 patients) currently receiving and responding to IVIg and the other
      half starting de novo on SCIg. Patients diagnosed with SPS according to defined sets of
      symptoms will be eligible to enroll.

      The primary clinical outcome will be based on clinical efficacy measures, as used before for
      the IVIg trial, based on changes in the Stiffness Index and Heightened Sensitivity scores,
      using the validated scales that the investigators have had previously utilized and validated
      (Dalakas et al 2001; see attached at the end of the protocol). These same measurements will
      be applied while on IVIg (weeks 0, 4, 8, 12) and will be compared to the measurements
      obtained during SCIg (weeks 16, 20, 24, 28). The secondary outcome will be Quality of Life
      (QoL) responses and patient preference for each treatment.
observational model: Cohort
time perspective: Prospective
measure: A >50% change from baseline on the Stiffness Index scores ( scale from 0-6; each item adds one) after 12 weeks of treatment.
time frame: 24 MONTHS
description: Proving that SCIg is as effective as IVIg on this clinical measure will be important for the patients who may have another treatment option avoiding the systemic side effects of IVIg
measure: A >50% change from baseline on the Heightened Sensitivity scores (scales from 1-7, each item adds one) after 12 weeks of treatment.
time frame: 24 months
description: Proving that SCIg is as effective as IVIg on this clinical measure will be important for the patients who may have another treatment option avoiding the systemic side effects of IVIg
measure: A meaningful change on Quality of Life (QoL) measures after 12 weeks of SCIg based on 6 sets of QoL Questionnaires (mobility, self-care, usual activities, pain, anxiety/depression, health state)
time frame: 24 MONTHS
description: Proving that SCIg affects Quality of life, as IVIg does, will be important for the patients who may have another treatment option avoiding the systemic side effects of IVIg
measure: If SCIg reduces the anti-GAD antibody titers measured in the patient's blood samples by more than 30%
time frame: 24 MONTHS
description: An effect on the circulating anti-Glutamic Acid Decarboxylase (GAD) antibodies will elucidate the mechanism of action of SCIg and any correlation between efficacy and antibody titers
measure: If >50% of patients prefer either SCIg or IVIg after 12 weeks of treatment based on a YES/NO questionnaire .
time frame: 24 MONTHS
description: Proving patients' preference is important because SCIg is self-administered at home and more convenient, without the need for hospitalizations.
arm group label: Patients receiving IVIg
description: Patients are currently receiving IVIg regularly for at least every 6 weeks and exhibit a favorable response will be recruited into the study (11 patients). They will be observed for 12 weeks under their existing IVIg regimen and will undergo measurements of their impairment using the previously validated Stiffness and Sensitivity scales and quality of life questionnaire (QoL) at weeks 0, 4, 8, 12. At week 12, prior to the first SCIg infusion, blood will be drawn for humoral (immunological) studies. One week following the last dose of IVIg (at week 13), the participants will be started on SCIg at a total dose equivalent to the monthly dose of IVIg they have been receiving.
arm group label: de novo SCIg patients/IVIg-Naive Group
description: This other arm of the trial will include 11 patients naïve to IVIg who do not receive other immunotherapies while being symptomatic. These patients after a 12-week observation period will start directly on SCIg drug (HYQVIA), following the same schedule as described above for the previous group.
intervention type: Biological
intervention name: HyQvia
description: Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase
arm group label: Patients receiving IVIg
arm group label: de novo SCIg patients/IVIg-Naive Group
Blood drawn for humoral (immunological) studies.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marinos C Dalakas, MD
phone: 2159557865
email: marinos.dalakas@jefferson.edu
last name: Vikram Puvenna
phone: 2159554672
email: vikram.puvenna@jefferson.edu
responsible party type: Sponsor
mesh term: Stiff-Person Syndrome
mesh term: Syndrome