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

Diabetes Autoimmunity Withdrawn in New Onset Patients (DAWN)


Lead sponsor: Tolerion, Inc.

Source Tolerion, Inc.
Brief Summary

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

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.

Overall Status Not yet recruiting
Start Date December 14, 2019
Completion Date December 14, 2023
Primary Completion Date December 14, 2021
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Treatment effect on log-transformed MMTT C-peptide area under the curve (AUC) 52 weeks
Secondary Outcome
Measure Time Frame
Rate of clinically important hypoglycemia 52 weeks
Rate of clinically important hypoglycemia 52 weeks
Daily Insulin requirements 52 weeks
Clinical Responder 52 weeks
Exogenous insulin-free at Week 52
Persistent Reduction at Week 52
GCM Measurement at Week 52
GCM Measurement at Week 52
GCM Measurement at Week 52
GCM Measurement at Week 52
GCM Measurement at Week 52
GCM Measurement at Week 52
Other measures of hypoglycemia at Week 52
Other measures of hypoglycemia at Week 52
Other measures of hypoglycemia at Week 52
Other measures of hypoglycemia at Week 52
Immunologic at Week 52
Immunologic at Week 52
Immunologic at Week 52
Immunologic at Week 52
Immunologic at Week 52
Immunologic at Week 52
Immunologic at Week 52
Enrollment 210

Intervention type: Biological

Intervention name: TOL-3021

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

Arm group label: TOL-3021

Intervention type: Other

Intervention name: TOL-3021 Placebo

Description: TOL-3021 Placebo

Arm group label: TOL-3021 Placebo

Other name: Placebo



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.

Gender: All

Minimum age: 12 Years

Maximum age: 35 Years

Healthy volunteers: No

Overall Contact

Last name: Nilay Shah, MD

Phone: +1 301-251-1161

Email: [email protected]

facility contact investigator
University of Miami Diabetes Research Institute Jay S Skyler, MD, MACP Jay S Skyler, MD,MACP Principal Investigator
Location Countries

United States

Verification Date

September 2019

Responsible Party

Responsible party type: Sponsor

Has Expanded Access
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: TOL-3021

Arm group type: Experimental

Description: TOL-3021 2 mg/mL

Arm group label: TOL-3021 Placebo

Arm group type: Placebo Comparator

Description: TOL-3021 Placebo

Acronym DAWN
Patient Data Undecided
Study Design Info

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

Primary purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Source: ClinicalTrials.gov