<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/NCT02204397</url>
  </required_header>
  <id_info>
    <org_study_id>JewishGH</org_study_id>
    <nct_id>NCT02204397</nct_id>
  </id_info>
  <brief_title>Study of Tolerability and Safety of Adding Ustekinumab to INGAP Peptide for 12 Weeks in Adult Patients With TD1 Melitis</brief_title>
  <official_title>A Single-center, Open-Label, Exploratory Study to Assess the Tolerability and Safety of the Addition of Ustekinumab to INGAP Peptide for 12 Weeks in Adult Patients With Type 1 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jewish General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jewish General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A proof-of-concept for safety and preliminary clinical efficacy of a combined regimen of&#xD;
      INGAP-P for β-cell regeneration and ustekinumab for IL-12-23 autoimmune modulation in&#xD;
      patients with established T1DM.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of this study is to assess the safety and tolerability of 12 weeks of&#xD;
      subcutaneous (SC) daily administration of INGAP-P (600 mg SC once a day in three separate&#xD;
      injection sites) with ustekinumab (two single injections of 45 mg SC, one as pretreatment two&#xD;
      weeks before INGAP-P treatment begins and the second one after 2 weeks of INGAP-P treatment)&#xD;
      in adult patients with established type 1 diabetes mellitus (T1DM). Safety will be evaluated&#xD;
      by assessing local tolerability, recording incidence of hypoglycemia, performing safety&#xD;
      laboratory measures at frequent intervals, and following subjects very closely for any&#xD;
      adverse events (AEs).&#xD;
&#xD;
      Secondary objectives of this study are to generate preliminary data on the efficacy of&#xD;
      INGAP-P and ustekinumab in adult patients with established T1DM, specifically by change from&#xD;
      baseline to Week 12 in: 1) Maximal C-peptide (Cmax) during mixed meal test (MMT) and glucagon&#xD;
      stimulated test (GST); 2) C-peptide release (AUC) during MMT and GST; 3) Fasting C-peptide;&#xD;
      4) Fasting glucose (before breakfast and after at least 8 hours of fasting); 5) Longer term&#xD;
      glycemic control as reflected by glycosylated hemoglobin (HbA1c) and 1,5-anhydroglucitol&#xD;
      (1,5-AG); and, 6) Total daily insulin dose relative to body weight.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2015</start_date>
  <completion_date type="Actual">March 8, 2017</completion_date>
  <primary_completion_date type="Actual">March 8, 2017</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>Safety and tolerability</measure>
    <time_frame>6 months</time_frame>
    <description>The tolerability of injections and general safety will be assessed on the basis of patient recorded diaries, assessments of cutaneous injection sites during clinic visits, clinical observations, severity of AEs recorded by the Medical Dictionary for Regulatory Activities (MedDRA), measurement of vital signs, physical examinations, electrocardiograms (ECGs), and clinical laboratory evaluations.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Composite C-Peptide efficacy according to specific parameters</measure>
    <time_frame>6 months</time_frame>
    <description>Composite secondary objectives of this study are to generate preliminary data on the efficacy of INGAP-P and ustekinumab in adult patients with established T1DM, specifically by change from baseline to Week 12-13 in:&#xD;
Maximal C-peptide (Cmax) during mixed meal test (MMT) and glucagon stimulated test (GST);&#xD;
C-peptide release (AUC) during MMT and GST;&#xD;
Fasting C-peptide;&#xD;
Fasting glucose (before breakfast and after at least 8 hours of fasting);&#xD;
Longer term glycemic control as reflected by glycosylated hemoglobin (HbA1c)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Type 1 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>INGAP Peptide, Ustekinumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>INGAP Peptide, Ustekinumab subcutaneous</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>INGAP Peptide, Ustekinumab</intervention_name>
    <arm_group_label>INGAP Peptide, Ustekinumab</arm_group_label>
    <other_name>INGAP Peptide</other_name>
    <other_name>Ustekinumab (Stelara)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female patients between the ages of 19 and 40 years old, inclusive, with a&#xD;
             history of T1DM for &gt;2 years and ≤20 years;&#xD;
&#xD;
          2. Female patients will not be breast-feeding during the study or within at least seven&#xD;
             days after the study is completed;&#xD;
&#xD;
          3. Receiving multiple daily insulin injections or insulin pump therapy for &gt;2 years;&#xD;
&#xD;
          4. Body mass index (BMI) ≤32 kg/m2 and total body weight &lt;100 kg;&#xD;
&#xD;
          5. HbA1c ≤8.2%,&#xD;
&#xD;
          6. Fasting C-peptide levels &gt;0.1 ng/mL and &lt;1.0 ng/mL;&#xD;
&#xD;
          7. CBC and platelet counts must be within normal limits, and specifically, the total&#xD;
             absolute neutrophil count must not be &lt;1500/μL;&#xD;
&#xD;
          8. Willing to sign the study informed consent document;&#xD;
&#xD;
          9. In good general health with no infections, active tuberculosis (TB), late severe&#xD;
             complications, or concomitant medical conditions that would influence the outcome of&#xD;
             the trial, at the discretion of the Investigator and the Sponsor;&#xD;
&#xD;
         10. If treated with angiotensin-converting enzymes/angiotensin II receptor blockers&#xD;
             (ACE/ARB), the doses should be unchanged for a month prior to enrollment;&#xD;
&#xD;
         11. Females of child bearing potential must have a negative urine pregnancy test on Day 0&#xD;
             prior to dispensing drug and should additionally fulfill one of the following&#xD;
             criteria:&#xD;
&#xD;
               -  Willing to use oral, implantable, transdermal, or injectable contraceptives for&#xD;
                  21 days prior to the first dose and until 28 days after the last dose; or,&#xD;
&#xD;
               -  Willing to use another reliable means of contraception approved by the&#xD;
                  Investigator (intrauterine device, female condom, diaphragm with spermicide,&#xD;
                  cervical cap, use of condom by sexual partner, or a sterile sexual partner) from&#xD;
                  Screening until after the last blood sample (at Week 16).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Total daily insulin dosage exceeding 1.0 U/kg/day or a change in total daily insulin&#xD;
             dose level of more than 50% (increase or decrease) within the past 3 months;&#xD;
&#xD;
          2. Treatment with any diabetes medication other than insulin;&#xD;
&#xD;
          3. A score of 4 or more restricted responses on the Clarke Hypoglycemia Awareness Survey;&#xD;
&#xD;
          4. Systolic or diastolic blood pressure &gt;180 mmHg or &gt;110 mmHg, respectively;&#xD;
&#xD;
          5. Clinical worsening of retinopathy or neuropathy in the previous 3 months;&#xD;
&#xD;
          6. Clinical worsening of nephropathy in the previous 3 months, or serum creatinine&#xD;
             exceeding 2.0 mg/dL,;&#xD;
&#xD;
          7. History or presence of acute or chronic pancreatitis, including a serum amylase level&#xD;
             &gt;1.5 times the upper limit of normal (ULN) or a serum lipase level &gt;2 times ULN;&#xD;
&#xD;
          8. Active infections at screening and during the study;&#xD;
&#xD;
          9. History of asthma;&#xD;
&#xD;
         10. History of TB;&#xD;
&#xD;
         11. Administration of bacille Calmette-Guérin (BCG) vaccine for TB during the one year&#xD;
             before the Screening Visit or one year after the last dose of ustekinumab;&#xD;
&#xD;
         12. A history or presence of any illness, disease, or condition (including cancer) that&#xD;
             could impact patient safety or evaluability of drug effect, in the Investigator&quot;s&#xD;
             opinion;&#xD;
&#xD;
         13. An episode of severe hypoglycemia (change in mental status requiring assistance)&#xD;
             during the previous 30 days;&#xD;
&#xD;
         14. An episode of acute glycemic decompensation with associated hyperosmolar non-ketotic&#xD;
             state or diabetic ketoacidosis during the past 6 months;&#xD;
&#xD;
         15. A serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total&#xD;
             bilirubin level &gt;2 times ULN;&#xD;
&#xD;
         16. Received any investigational product within 30 days of admission into this study or&#xD;
             had any prior or existing exposure to INGAP-P, glucagon-like peptides (GLP-1, GLP-2,&#xD;
             or analogs), ustekinumab, or TNF blocking agents (Patients that participated in the&#xD;
             placebo group of previous INGAP-P study E-201 are not excluded from this study.);&#xD;
&#xD;
         17. Known hypersensitivity to INGAP-P or any excipient used in the formulation;&#xD;
&#xD;
         18. Known hypersensitivity to ustekinumab or any components of the product;&#xD;
&#xD;
         19. Concurrent or planned participation in any other clinical study during the conduct of&#xD;
             this study;&#xD;
&#xD;
         20. Positive urine test for cocaine, opiates, amphetamines, or cannabinoids;&#xD;
&#xD;
         21. Inability to fill out and maintain a daily diary during the screening period prior to&#xD;
             dosing;&#xD;
&#xD;
         22. Human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis&#xD;
             C seropositivity in blood sample taken during screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>George Tsoukas, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Endocrinology and Metabolism, Montreal General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Montreal General Hospital</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3G 1A4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>July 28, 2014</study_first_submitted>
  <study_first_submitted_qc>July 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 30, 2014</study_first_posted>
  <last_update_submitted>May 25, 2017</last_update_submitted>
  <last_update_submitted_qc>May 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 30, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Jewish General Hospital</investigator_affiliation>
    <investigator_full_name>Lawrence Rosenberg</investigator_full_name>
    <investigator_title>Executive Director</investigator_title>
  </responsible_party>
  <keyword>Type 1 Diabetes mellitus</keyword>
  <keyword>INGAP</keyword>
  <keyword>Ustekinumab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ustekinumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>IPD sharing is still under review and will be determined at a later date</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02204397
org study id: JewishGH
nct id: NCT02204397
lead sponsor: 
has dmc: No
A proof-of-concept for safety and preliminary clinical efficacy of a combined regimen of
      INGAP-P for β-cell regeneration and ustekinumab for IL-12-23 autoimmune modulation in
      patients with established T1DM.
The primary objective of this study is to assess the safety and tolerability of 12 weeks of
      subcutaneous (SC) daily administration of INGAP-P (600 mg SC once a day in three separate
      injection sites) with ustekinumab (two single injections of 45 mg SC, one as pretreatment two
      weeks before INGAP-P treatment begins and the second one after 2 weeks of INGAP-P treatment)
      in adult patients with established type 1 diabetes mellitus (T1DM). Safety will be evaluated
      by assessing local tolerability, recording incidence of hypoglycemia, performing safety
      laboratory measures at frequent intervals, and following subjects very closely for any
      adverse events (AEs).

      Secondary objectives of this study are to generate preliminary data on the efficacy of
      INGAP-P and ustekinumab in adult patients with established T1DM, specifically by change from
      baseline to Week 12 in: 1) Maximal C-peptide (Cmax) during mixed meal test (MMT) and glucagon
      stimulated test (GST); 2) C-peptide release (AUC) during MMT and GST; 3) Fasting C-peptide;
      4) Fasting glucose (before breakfast and after at least 8 hours of fasting); 5) Longer term
      glycemic control as reflected by glycosylated hemoglobin (HbA1c) and 1,5-anhydroglucitol
      (1,5-AG); and, 6) Total daily insulin dose relative to body weight.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and tolerability
time frame: 6 months
description: The tolerability of injections and general safety will be assessed on the basis of patient recorded diaries, assessments of cutaneous injection sites during clinic visits, clinical observations, severity of AEs recorded by the Medical Dictionary for Regulatory Activities (MedDRA), measurement of vital signs, physical examinations, electrocardiograms (ECGs), and clinical laboratory evaluations.
measure: Composite C-Peptide efficacy according to specific parameters
time frame: 6 months
description: Composite secondary objectives of this study are to generate preliminary data on the efficacy of INGAP-P and ustekinumab in adult patients with established T1DM, specifically by change from baseline to Week 12-13 in:
Maximal C-peptide (Cmax) during mixed meal test (MMT) and glucagon stimulated test (GST);
C-peptide release (AUC) during MMT and GST;
Fasting C-peptide;
Fasting glucose (before breakfast and after at least 8 hours of fasting);
Longer term glycemic control as reflected by glycosylated hemoglobin (HbA1c)
arm group label: INGAP Peptide, Ustekinumab
arm group type: Experimental
description: INGAP Peptide, Ustekinumab subcutaneous
intervention type: Drug
intervention name: INGAP Peptide, Ustekinumab
arm group label: INGAP Peptide, Ustekinumab
other name: INGAP Peptide
other name: Ustekinumab (Stelara)
criteria: 
gender: All
minimum age: 19 Years
maximum age: 40 Years
healthy volunteers: No
last name: George Tsoukas, MD
role: Principal Investigator
affiliation: Department of Endocrinology and Metabolism, Montreal General Hospital
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Jewish General Hospital
investigator full name: Lawrence Rosenberg
investigator title: Executive Director
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Ustekinumab
sharing ipd: Undecided
ipd description: IPD sharing is still under review and will be determined at a later date