Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    sunrise | Recruiting, Not yet recruiting Studies | diabetes | Asheville, North Carolina, U.S.
Previous Study | Return to List | Next Study

Diabetes Autoimmunity Withdrawn In New Onset and In Established Patients (SUNRISE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03895437
Recruitment Status : Recruiting
First Posted : March 29, 2019
Last Update Posted : September 26, 2019
Sponsor:
Information provided by (Responsible Party):
Tolerion, Inc.

Brief Summary:
TThe study is a prospective, randomized, 52-week double-blind, placebo-controlled, multicenter trial in subjects with T1D followed by a 2-year safety follow-up.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Biological: TOL-3021 Other: TOL-3021 Placebo Phase 2

Detailed Description:
The SUNRISE study is a prospective, multi-center, double-blind, randomized, placebo-controlled trial in subjects aged 18.0 to <41.0 years diagnosed with T1D, as defined by American Diabetes Association (ADA) criteria, and within 5 years of diagnosis. Time of diagnosis is defined as the first day of insulin administration. Subjects will be stratified by duration (zero up to 1 year and 1 year up to five years) to ensure balance of disease duration across treatment and placebo groups in each strata. Subjects should be randomized no sooner than 6 weeks after diagnosis, unless blood glucose is adequately controlled for >14 days, defined as 3 consecutive fasting glucose levels by SMBG or lab testing <130 mg/dL. Screening assessments will include a physical examination, an ophthalmic examination, chemistry and hematology safety labs, urinalysis, 24-hour urine protein and creatinine, HbA1c, presence of T1D antibodies, and an MMTT. Approximately 51 qualified subjects who meet all selection criteria will be randomized in a 2:1 ratio to treatment with TOL-3021 or placebo and treated for 52 weeks. Subjects will agree to diabetes management during the study with the goal of maintaining HbA1c levels of approximately 7.0% without frequent episodes of hypoglycemia.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Subjects will be randomly assigned to treatment with TOL-3021 or placebo in a 2:1 fashion
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2 Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety of TOL-3021 in Patients With New Onset or Established Type 1 Diabetes Mellitus
Actual Study Start Date : June 17, 2019
Estimated Primary Completion Date : August 14, 2021
Estimated Study Completion Date : August 14, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Experimental: TOL-3021
TOL-3021 2 mg/mL
Biological: TOL-3021
TOL-3021 1 mg is a bacterial plasmid expression vector containing the coding sequences for the human proinsulin (hINS) gene.

Placebo Comparator: TOL-3021 Placebo
TOL-3021 Placebo
Other: TOL-3021 Placebo
TOL-3021 Placebo
Other Name: Placebo




Primary Outcome Measures :
  1. Treatment effect on log-transformed MMTT C-peptide area under the curve (AUC) [ Time Frame: 52 weeks ]
    The primary outcome is the treatment effect on log-transformed MMTT C-peptide area under the curve (AUC)


Secondary Outcome Measures :
  1. Rate of clinically important hypoglycemia [ Time Frame: 52 weeks ]
    glucometer, a single blood glucose level

  2. Rate of clinically important hypoglycemia [ Time Frame: 52 weeks ]
    CGM, ≥15 consecutive minutes with glucose <54 mg/dL

  3. Daily Insulin requirements [ Time Frame: 52 weeks ]
    Total daily insulin requirements in units per kilogram (kg) body weight

  4. Clinical Responder [ Time Frame: 52 weeks ]
    A clinical responder analysis will be undertaken as a secondary endpoint to further characterize the treatment effect on a clinical level. A positive responder outcome will be defined as no change or increase in C-peptide AUC from baseline vs. Week 52

  5. Proportion of subjects in each treatment arm who are exogenous insulin-free for at least 3 months with HbA1c levels less than 6.5% [ Time Frame: at Week 52 ]
    Proportion of subjects in each treatment arm who are exogenous insulin-free for at least 3 months with HbA1c levels less than 6.5%

  6. GCM Measurement [ Time Frame: at Week 52 ]
    Time in range 70-80 mg/dL

  7. GCM Measurement [ Time Frame: at Week 52 ]
    Time in range 70-180 mg/dL

  8. GCM Measurement [ Time Frame: at Week 52 ]
    Time >180 mg/dL

  9. GCM Measurement [ Time Frame: at Week 52 ]
    Time >250 mg/dL

  10. GCM Measurement [ Time Frame: at Week 52 ]
    Mean Glucose Coefficient of Variation

  11. GCM Measurement [ Time Frame: at Week 52 ]
    Low Blood Glucose Index (LBGI)

  12. GCM Measurement [ Time Frame: at Week 52 ]
    Glucose below 70 mg/dL Area Over the Curve (AOC70)

  13. Other measures of hypoglycemia [ Time Frame: at Week 52 ]
    Severe hypoglycemia (SH) events (impaired or loss of consciousness requiring assistance of another)

  14. Other measures of hypoglycemia [ Time Frame: at Week 52 ]
    Documented symptomatic hypoglycemia (an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration <70 mg/dl (3.9 mmol/L))

  15. Other measures of hypoglycemia [ Time Frame: at Week 52 ]
    Total time <70 mg/dL by CGM

  16. Other measures of hypoglycemia [ Time Frame: at Week 52 ]
    Nocturnal hypoglycemia, severe or documented symptomatic episodes (as defined above) occurring after the subject has retired for the primary sleeping period

  17. Immunologic - specific autoantigen tolerance [ Time Frame: at Week 52 ]
    Quantum dot (Q-dot) responses within the qualifying subpopulation to confirm induction of specific autoantigen tolerance

  18. Immunologic - specific autoantigen tolerance [ Time Frame: at Week 52 ]
    Comparison of quantum dot responses within the qualifying subpopulation to clinical outcomes to confirm correlation with specific autoantigen tolerance

  19. Immunologic - immune response to proinsulin/insulin [ Time Frame: at Week 52 ]
    Determine the effect of treatment on and predictive value of regulatory/protective humoral immune response to proinsulin/insulin

  20. Immunologic - serum insulin autoantibody affinity [ Time Frame: at Week 52 ]
    Determine the effect of treatment on and predictive value of serum insulin autoantibody affinity for subjects

  21. Immunologic - insulin autoantibody isotypes [ Time Frame: at Week 52 ]
    Determine the effect of treatment on and predictive value of insulin autoantibody isotypes (IgA and IgM) and IgG subclasses

  22. Immunologic - ECL assay for serum insulin antibodies [ Time Frame: at Week 52 ]
    Determine the effect of treatment on and predictive value of serum insulin by highly sensitive ECL assay

  23. Immunologic - ECL assay for glutamic acid decarboxylase antibodies [ Time Frame: at Week 52 ]
    Determine the effect of treatment on and predictive value of glutamic acid decarboxylase by highly sensitive ECL assay

  24. Immunologic - ECL assay for IA-2 antibodies [ Time Frame: at Week 52 ]
    Determine the effect of treatment on and predictive value of IA-2 by highly sensitive ECL assay

  25. Immunologic - ECL assay for ZnT8 antibodies [ Time Frame: at Week 52 ]
    Determine the effect of treatment on and predictive value of ZnT8 antibodies by highly sensitive ECL assay

  26. Immunologic - serum insulin antibodies [ Time Frame: at Week 52 ]
    Determine the effect of treatment on and predictive value of competition assays of serum insulin

  27. Immunologic - proinsulin IgM antibodies [ Time Frame: at Week 52 ]
    Determine the effect of treatment on and predictive value of competition assays of proinsulin IgM

  28. Immunologic - proinsulin IgG antibodies [ Time Frame: at Week 52 ]
    Determine the effect of treatment on and predictive value of competition assays of proinsulin IgG antibodies



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of Type 1 Diabetes Mellitus based on American Diabetes Association (ADA) criteria and within 5.0 years from diagnosis, defined as the first day of insulin administration.
  2. Age at randomization of 18.0 - <41.0 years of age .
  3. Adequate glycemic control as defined by HbA1c <7.6% based on point-of-care or local lab measurement and time in glycemic range (70-180 mg/dL) >55% by CGM recording over 3 or more days within 5 days of baseline mixed meal tolerance test (MMTT).
  4. On insulin therapy (total insulin dose >0.125 U/kg BW)
  5. Presence of antibodies to at least one of the following antigens: GAD-65, IA-2, ZnT8, or insulin, or documentation of positive antibodies.
  6. Peak C-peptide during screening 4-hour mixed meal tolerance test (MMTT) ≥ 0.2pmol/mL.
  7. Willingness to wear the Dexcom G6 continuous glucose monitoring (CGM) device and use according to instructions most of each day from screening to end of treatment period.
  8. Written informed consent, including authorization to release health information.
  9. Willingness and ability of subject to comply with all study procedures of the study protocol, including attending all clinic visits.

Exclusion Criteria:

  1. Body Mass Index (BMI) >32 kg/m2
  2. Previous immunotherapy for T1D.
  3. Diagnosis of liver disease or hepatic enzymes, as defined by ALT and/or AST ≥ 2.5 times the upper limit of normal (ULN).
  4. Hematology: white blood cells (WBC) <3 x 109/L; platelets <100 x 109/L; hemoglobin <10.0 g/dL. (Low WBC values may be repeated every 3-7 days, and results to be discussed with the Medical Monitor.)
  5. Latent autoimmune diabetes of adults (LADA), which is generally associated with preceding history and treatment of T2D.
  6. Estimated glomerular filtration rate (eGFR) <60 ml/min.
  7. History of malignancy, except for cancers in remission >5 years, or basal cell or in situ squamous cell carcinoma of the skin.
  8. Significant cardiovascular disease (including inadequately controlled hypertension), history of myocardial infarction, angina, use of anti-anginal medicines (e.g., nitroglycerin), or abnormal stress test, which, in the opinion of the Principal Investigator (PI), would interfere with participation in the trial.
  9. Immunosuppressive therapy (systemic corticosteroids, cyclosporine, azathioprine, or biologics) within 30 days of screening.
  10. Current or prior (within the last 30 days) use of metformin, sulfonylureas, glinides, thiazolidinediones, GLP1-RAs, DPP-IV inhibitors, pramlintide, or SGLT-2 inhibitors.
  11. Current use of verapamil or α-methyldopa.
  12. History of any organ transplant, including islet cell transplant.
  13. Asthma that requires oral glucocorticoid therapy. Inhaled glucocorticoid therapy is permitted.
  14. Active autoimmune or immune deficiency disorder other than T1D or well-controlled autoimmune conditions (e.g., thyroid disease, celiac disease, and sarcoidosis) Generally excluded conditions include rheumatoid arthritis, moderate-to-severe psoriasis, inflammatory bowel disease, and other autoimmune conditions that may require treatment with TNF or other biologics), unless approved by the Medical Monitor.
  15. Thyroid-stimulating hormone (TSH) at screening >7.5 mIU/L.
  16. History of adrenal insufficiency.
  17. Moderate non-proliferative retinopathy" (NPDR) or proliferative retinopathy
  18. Evidence of infection with HBV (as defined by hepatitis B surface antigen, HBsAg), HCV (anti-HCV antibodies), or HIV.
  19. Subject is breastfeeding.
  20. Positive urine pregnancy test: Females of childbearing potential must be excluded if they have a positive urine pregnancy test at screening or randomization or if they are not using medically acceptable methods of birth control. Acceptable methods of birth control include oral or transdermal contraceptives, condom, spermicidal foam, IUD, progestin implant or injection, abstinence, vaginal ring, or sterilization of partner. The reason for non-childbearing potential, such as bilateral tubal ligation, bilateral oophorectomy, hysterectomy, or 1 year or more postmenopausal must be specified in the subject's Case Report Form (CRF).
  21. 21. Males of reproductive potential who are unwilling to use medically acceptable birth control, unless the female partner is postmenopausal or surgically sterile.
  22. Any social condition or medical condition that would, in the opinion of the PI, prevent complete participation in the study or would pose a significant hazard to the subject's participation.
  23. Anticipated major surgery during the duration of the trial, which could interfere with participation in the trial.
  24. History of drug or alcohol dependence within 12 months of screening.
  25. Psychiatric disorder that would prevent subjects from giving informed consent.
  26. Household members of current participants in this protocol.
  27. Subjects who are not fluent in the English language.
  28. Participation in other studies involving the administration of an investigational drug or device, including the administration of an experimental agent for T1D, at any time, or use of an experimental device for T1D within 30 days prior to screening, unless approved by the Medical Monitor.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03895437


Contacts
Layout table for location contacts
Contact: Nilay Project Director 301.251.1161 tol3021@emmes.com
Contact: Anne Project Manager 301.251.1161 tol3021@emmes.com

Locations
Layout table for location information
United States, California
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Trudy Esrey    650-498-4450    tesrey@stanford.edu   
Principal Investigator: Darrell Wilson, MD         
United States, Connecticut
Chase Medical Research, LLC Not yet recruiting
Hamden, Connecticut, United States, 06517
Contact: Melissa Capasso       mcapasso@chasemr.com   
Principal Investigator: Joseph Soufer, MD         
United States, Florida
Baptist Health Research Institute Not yet recruiting
Jacksonville, Florida, United States, 32258
Contact: Kristy Clemmer    904-271-6363    Kristina.Clemmer@bmcjax.com   
Contact: Alan Cleland, MD         
Principal Investigator: Alan Cleland, MD         
University of Miami Diabetes Research Institute Not yet recruiting
Miami, Florida, United States, 33101-6960
Contact: Jay S Skyler, MD, MACP         
Principal Investigator: Jay S Skyler, MD,MACP         
United States, Iowa
Iowa Diabetes and Endocrinology Research Center Recruiting
West Des Moines, Iowa, United States, 50256
Contact: Tara Herrold    515-329-6803    therrold@iowadiabetes.com   
Principal Investigator: Anuj Bhargava, MD         
United States, New York
Naomi Berrie Diabetes Center, Columbia University Recruiting
New York, New York, United States, 10032
Contact: Sarah Pollack    212-851-5425    sjp2174@columbia.edu   
Principal Investigator: Robin Goland, MD         
SUNY Upstate Medical University Not yet recruiting
Syracuse, New York, United States, 13210
Contact: Jane Bulger    315-464-9008    bulgerj@upstate.edu   
Principal Investigator: Ruth Weinstock, MD         
United States, North Carolina
Mountain Diabetes and Endocrine Center Recruiting
Asheville, North Carolina, United States, 28803
Contact: Will Cooley    828-684-9588 ext 315    wcooley@mdecresearch.com   
Principal Investigator: Wendy Lane, MD         
University of North Carolina Diabetes Care Center Not yet recruiting
Chapel Hill, North Carolina, United States, 27517
Contact: Julie Uehling    984-974-3010    julie_uehling@med.unc.edu   
Principal Investigator: John Buse, MD         
United States, Texas
Diabetes and Glandular Disease Clinic, P.A. Recruiting
San Antonio, Texas, United States, 78229
Contact: Terri Ryan    210-614-8612 ext 1630    terri.ryan@dgdclinic.com   
Principal Investigator: Mark Kipnes, M.D.         
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22903
Contact: Mary Voelmle    434-924-2327    MKV9F@hscmail.mcc.virginia.edu   
Principal Investigator: Sue Brown, MD         
Sponsors and Collaborators
Tolerion, Inc.

Layout table for additonal information
Responsible Party: Tolerion, Inc.
ClinicalTrials.gov Identifier: NCT03895437     History of Changes
Other Study ID Numbers: TOL-3021-231
First Posted: March 29, 2019    Key Record Dates
Last Update Posted: September 26, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: We recognize that sharing anonymized data and other information from clinical trials can increase the speed and success of biomedical research in addressing unmet clinical need. We are following ongoing discussions among industry, the academic community, and other stakeholders regarding data sharing. Industry and its academic partners have not yet formulated a consensus on the amount, types, and forms of data that will be useful and beneficial to the public, or the process for sharing data. As a small, young company, we await the development of guidances and best practices for industry before issuing a comprehensive data sharing plan. For now, we defer a description of what data will be shared and the process for doing so. The protocol will be shared as part of study publication in a peer reviewed medical journal. The protocol will be available as a supplement to the publication and/or on the website of the publishing journal and upon request to the Sponsor (www.tolerion.bio)

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tolerion, Inc.:
Type 1 Diabetes
Diabetes
Diabetes Mellitus
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases