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Diabetes Mellitus, Type 1Phase 2DAWNNCT03794973

Diabetes Autoimmunity Withdrawn in New Onset Patients (DAWN)

A Phase 2 study testing TOL-3021 in people with Diabetes Mellitus, Type 1, run by Tolerion, Inc. at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The study is a prospective, randomized, double-blind, placebo-controlled, multi-center trial in subjects with new onset T1D. Read more about this study

Who is it for?
Ages 12 to 35 years
Conditions the study is for
Diabetes Mellitus, Type 1
What is being tested?
TOL-3021
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
1 siteUnited States
Study dates
14 Dec 2019to 14 Dec 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 35 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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) .
  • 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.
  • Age at randomization of 12.0 - <18.0 years (adolescent), 18.0 - <36.0 years of age (adult) ..
  • HbA1c <10.0% based on point-of-care or local lab measurement.
  • Measurement can be repeated every 5-7 days if >10.0%.
  • 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.
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  • Willingness to wear a continuous glucose monitoring (CGM) device for specified periods of time.
  • Written informed consent, including authorization to release health information and assent for adolescent subjects.
  • Willingness and ability of subject or adult guardian to comply with all study procedures of the study protocol, including attending all clinic visits.

Who cannot join

  • Body Mass Index (BMI) >30 kg/m2 for adults; >95 percentile BMI-for-age for subjects under 18 years of age.
  • Previous immunotherapy for T1D.
  • Diagnosis of liver disease or hepatic enzymes, as defined by ALT and/or AST ≥2.5 times the upper limit of normal (ULN).
  • 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.)
  • Serum creatinine > 1.5 times ULN.
  • History of malignancy, except for cancers in remission >5 years, or basal cell or in situ squamous cell carcinoma of the skin.
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  • 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.
  • Immunosuppressive therapy (systemic corticosteroids, cyclosporine, azathioprine, or biologics) within 30 days of screening.
  • Current or prior (within the last 30 days) use of metformin, sulfonylureas, glinides, thiazolidinediones, GLP1-RAs, DPP-IV inhibitors, pramlintide, or SGLT-2 inhibitors.
  • Current use of verapamil or α-methyldopa.
  • History of any organ transplant, including islet cell transplant.
  • 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.
  • Thyroid-stimulating hormone (TSH) at screening >2.5 mIU/L.
  • History of adrenal insufficiency.
  • Evidence of infection with HBV (as defined by hepatitis B surface antigen (HBsAg)), HCV (anti-HCV antibodies), or HIV.
  • 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).
  • Males of reproductive potential who are unwilling to use medically acceptable birth control, unless the female partner is postmenopausal or surgically sterile.
  • 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.
  • Anticipated major surgery during the duration of the trial, which could interfere with participation in the trial.
  • History of drug or alcohol dependence within 12 months of screening.
  • Psychiatric disorder that would prevent subjects from giving informed consent.
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Miami Diabetes Research Institute

    Miami, Florida, 33101-6960

Other trials in United States

About this study

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

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

Read the 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.

Being tested
TOL-3021, TOL-3021 Placebo
Keywords
Type 1 Diabetes, Diabetes, Diabetes Mellitus
Medical subject headings
Diabetes Mellitus, Type 1, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TOL-3021Biological

    TOL-3021 1 mg is a bacterial plasmid expression vector containing the coding sequences for the human proinsulin (hINS) gene.

  • TOL-3021 PlaceboOther

    Also called Placebo

    TOL-3021 Placebo

Study groups in NCT03794973
Study groupRoleWhat they receive
TOL-3021ExperimentalTOL-3021 2 mg/mL
Receives: Biological: TOL-3021
TOL-3021 PlaceboPlacebo comparatorTOL-3021 Placebo
Receives: Other: TOL-3021 Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Treatment effect on log-transformed MMTT C-peptide area under the curve (AUC)

    The primary outcome is the treatment effect on log-transformed MMTT C-peptide area under the curve (AUC)

    Measured: 52 weeks

Secondary outcomes (23)

  1. Rate of clinically important hypoglycemia

    glucometer, a single blood glucose level

    Measured: 52 weeks

  2. Rate of clinically important hypoglycemia

    CGM, ≥15 consecutive minutes with glucose <54 mg/dL

    Measured: 52 weeks

  3. Daily Insulin requirements

    Total daily insulin requirements in units per kilogram (kg) body weight

    Measured: 52 weeks

  4. Clinical Responder

    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

    Measured: 52 weeks

  5. Exogenous insulin-free

    Proportion of subjects in each treatment arm who are exogenous insulin-free for at least 3 months with HbA1c levels less than 6.5%

    Measured: at Week 52

  6. Persistent Reduction

    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

    Measured: at Week 52

  7. GCM Measurement

    Time in range 70-80 mg/dL

    Measured: at Week 52

  8. GCM Measurement

    Time >180 mg/dL

    Measured: at Week 52

  9. GCM Measurement

    Time >250 mg/dL

    Measured: at Week 52

  10. GCM Measurement

    Mean Glucose Coefficient of Variation

    Measured: at Week 52

  11. GCM Measurement

    Low Blood Glucose Index (LBGI)

    Measured: at Week 52

  12. GCM Measurement

    Glucose below 70 mg/dL Area Over the Curve (AOC70)

    Measured: at Week 52

  13. Other measures of hypoglycemia

    Severe hypoglycemia (SH) events (impaired or loss of consciousness requiring assistance of another)

    Measured: at Week 52

  14. Other measures of hypoglycemia

    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))

    Measured: at Week 52

  15. Other measures of hypoglycemia

    Total time <70 mg/dL by CGM

    Measured: at Week 52

  16. Other measures of hypoglycemia

    Nocturnal hypoglycemia, severe or documented symptomatic episodes (as defined above) occurring after the subject has retired for the primary sleeping period

    Measured: at Week 52

  17. Immunologic

    Quantum dot (Q-dot) responses within the qualifying subpopulation to confirm induction of specific autoantigen tolerance

    Measured: at Week 52

  18. Immunologic

    Comparison of quantum dot responses within the qualifying subpopulation to clinical outcomes to confirm correlation with specific autoantigen tolerance

    Measured: at Week 52

  19. Immunologic

    Determine the effect of treatment on and predictive value of regulatory/protective humoral immune response to proinsulin/insulin

    Measured: at Week 52

  20. Immunologic

    Determine the effect of treatment on and predictive value of serum insulin autoantibody affinity for subjects

    Measured: at Week 52

  21. Immunologic

    Determine the effect of treatment on and predictive value of insulin autoantibody isotypes (IgA and IgM) and IgG subclasses

    Measured: at Week 52

  22. Immunologic

    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

    Measured: at Week 52

  23. Immunologic

    Determine the effect of treatment on and predictive value of competition assays of serum insulin and proinsulin IgM and IgG antibodies

    Measured: at Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jan 2019
  2. Study start14 Dec 2019 (estimated)
  3. Primary completion14 Dec 2021 (estimated)
  4. Study completion14 Dec 2023 (estimated)

Why it stopped: Modification to Clinical Development Plan

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Subjects will be randomly assigned to treatment with TOL-3021 or placebo in a 2:1 fashion
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03794973
Sponsor's protocol ID
TOL-3021-220
Acronym
DAWN
Status last verified
Dec 2020
First submitted
3 Jan 2019
Last updated
8 Dec 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TOL-3021 in people with Diabetes Mellitus, Type 1, run by Tolerion, Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 8 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment effect on log-transformed MMTT C-peptide area under the curve (AUC) (time frame: 52 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03794973.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2020.

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