We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

Diabetes Autoimmunity Withdrawn in New Onset Patients (DAWN) (DAWN)

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. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03794973
Recruitment Status : Withdrawn (Modification to Clinical Development Plan)
First Posted : January 7, 2019
Last Update Posted : December 8, 2020
Information provided by (Responsible Party):
Tolerion, Inc.

Brief Summary:
The study is a prospective, randomized, double-blind, placebo-controlled, multi-center trial in subjects with new onset T1D.

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

Detailed Description:
The study will include 210 male or female subjects aged 12 to 35 years diagnosed with T1D, as defined by the American Diabetes Association (ADA) criteria and meeting enrollment criteria as follows. Initial enrollment will be restricted to subjects aged 18 and older until an analysis of data from subjects with 3 months' exposure to drug confirms safety. Upon completion of this assessment, enrollment will be open without further restrictions for subjects aged 12-35.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 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 2b Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Efficacy of TOL-3021 in Patients With New Onset Type 1 Diabetes Mellitus
Estimated Study Start Date : December 14, 2019
Estimated Primary Completion Date : December 14, 2021
Estimated Study Completion Date : December 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. Exogenous insulin-free [ 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. Persistent Reduction [ Time Frame: at Week 52 ]
    Proportion of subjects in each treatment arm who achieve a persistent reduction for at least 3 months in insulin dose to <0.5 units/kg

  7. GCM Measurement [ Time Frame: at Week 52 ]
    Time in range 70-80 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 [ Time Frame: at Week 52 ]
    Quantum dot (Q-dot) responses within the qualifying subpopulation to confirm induction of specific autoantigen tolerance

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

  21. Immunologic [ 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 [ Time Frame: at Week 52 ]
    Determine the effect of treatment on and predictive value of serum insulin, glutamic acid decarboxylase, IA-2, and ZnT8 antibodies by highly sensitive ECL assay

  23. Immunologic [ Time Frame: at Week 52 ]
    Determine the effect of treatment on and predictive value of competition assays of serum insulin and proinsulin IgM and 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:   12 Years to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Diagnosis of Type 1 Diabetes Mellitus based on American Diabetes Association (ADA) criteria and ≤100 days since diagnosis, defined as the first day of insulin administration (subjects must be able to be randomized within the 100-day period from diagnosis) .
  2. Adequate glycemic control for >14 days, defined as 3 consecutive fasting glucose levels by self-administered blood glucose (SMBG) or lab testing at <130 mg/dL.
  3. Age at randomization of 12.0 - <18.0 years (adolescent), 18.0 - <36.0 years of age (adult) ..
  4. HbA1c <10.0% based on point-of-care or local lab measurement.

    • Measurement can be repeated every 5-7 days if >10.0%.

  5. Presence of antibodies to at least one of the following antigens: GAD-65, IA-2, ZnT8; or insulin, if obtained within 10 days of the onset of exogenous insulin therapy.
  6. Willingness to wear a continuous glucose monitoring (CGM) device for specified periods of time.
  7. Written informed consent, including authorization to release health information and assent for adolescent subjects.
  8. Willingness and ability of subject or adult guardian to comply with all study procedures of the study protocol, including attending all clinic visits.

Exclusion Criteria:

  1. Body Mass Index (BMI) >30 kg/m2 for adults; >95 percentile BMI-for-age for subjects under 18 years of age.
  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. Serum creatinine > 1.5 times ULN.
  6. History of malignancy, except for cancers in remission >5 years, or basal cell or in situ squamous cell carcinoma of the skin.
  7. 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.
  8. Immunosuppressive therapy (systemic corticosteroids, cyclosporine, azathioprine, or biologics) within 30 days of screening.
  9. Current or prior (within the last 30 days) use of metformin, sulfonylureas, glinides, thiazolidinediones, GLP1-RAs, DPP-IV inhibitors, pramlintide, or SGLT-2 inhibitors.
  10. Current use of verapamil or α-methyldopa.
  11. History of any organ transplant, including islet cell transplant.
  12. Active autoimmune or immune deficiency disorder other than T1D or well-controlled autoimmune thyroid disease (e.g., sarcoidosis, 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.
  13. Thyroid-stimulating hormone (TSH) at screening >2.5 mIU/L.
  14. History of adrenal insufficiency.
  15. Evidence of infection with HBV (as defined by hepatitis B surface antigen (HBsAg)), HCV (anti-HCV antibodies), or HIV.
  16. 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, intrauterine device (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).
  17. Males of reproductive potential who are unwilling to use medically acceptable birth control, unless the female partner is postmenopausal or surgically sterile.
  18. 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.
  19. Anticipated major surgery during the duration of the trial, which could interfere with participation in the trial.
  20. History of drug or alcohol dependence within 12 months of screening.
  21. Psychiatric disorder that would prevent subjects from giving informed consent.
  22. 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): NCT03794973

Layout table for location information
United States, Florida
University of Miami Diabetes Research Institute
Miami, Florida, United States, 33101-6960
Sponsors and Collaborators
Tolerion, Inc.
Layout table for additonal information
Responsible Party: Tolerion, Inc.
ClinicalTrials.gov Identifier: NCT03794973    
Other Study ID Numbers: TOL-3021-220
First Posted: January 7, 2019    Key Record Dates
Last Update Posted: December 8, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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 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