Diabetes AutoimmunitY Withdrawn in Established Patients (DAY)

NCT03794960 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: TOL-3021-230
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The study is a prospective, randomized, double-blind, placebo-controlled, multicenter trial in subjects with established T1D.

Conditions

Diabetes Mellitus, Type 1

Keywords

Diabetes; Type 1 Diabetes; Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Treatment Effect

  The primary outcome is the treatment effect on log-transformed MMTT C-peptide area under the curve (AUC) after 52 weeks of TOL-3021 treatment

  at Week 52

Secondary Outcomes (22)

• Rate of Clinically important hypoglycemia as defined by measured glucose value of <54 mg/dL (3.0 mM/L)

  at Week 52

• Rate of Clinically important hypoglycemia as defined by measured glucose value of <54 mg/dL (3.0 mM/L)

  at Week 52

• Rate of Clinically important hypoglycemia as defined by measured glucose value of <54 mg/dL (3.0 mM/L)

  at Week 52

• Rate of Clinically important hypoglycemia as defined by measured glucose value of <54 mg/dL (3.0 mM/L)

  at Week 52

• Clinical responder analysis

  at Week 52

Study Arms (2)

TOL-3021

EXPERIMENTAL

Biological: TOL-3021

TOL-3021 Placebo

PLACEBO COMPARATOR

Other: TOL-3021 Placebo

Interventions

TOL-3021 BIOLOGICAL

A plasmid expression vector containing the coding sequences for full-length human proinsulin.

TOL-3021

TOL-3021 Placebo OTHER

TOL-3021 Placebo

Also known as: Placebo

TOL-3021 Placebo

Eligibility Criteria

• Age: 12 Years - 36 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of Type 1 Diabetes Mellitus based on American Diabetes Association (ADA) criteria and within 1.0 to 5.0 years from diagnosis, defined as the first day of insulin administration.
• Adequate glycemic control for \>14 days, defined as 3 consecutive fasting glucose levels by self-administered blood glucose (SMBG) or lab testing \<130 mg/dL.
• Age at randomization of 12.0 - \<18.0 years (adolescent), 18.0 - \<36.0 years of age (adult) .
• HbA1c \<8.5% based on point-of-care or local lab measurement.
• Measurement can be repeated every 5-7 days if \>8.5%.
• Presence of antibodies to at least one of the following antigens: GAD-65, IA-2, ZnT8; or insulin.
• Peak C-peptide during screening 4-hour mixed meal tolerance test (MMTT) ≥ 0.2pmol/mL.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Tolerion, Inc.: lead

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2019
• First Posted: January 7, 2019
• Study Start: December 14, 2019
• Primary Completion: December 14, 2021
• Study Completion: December 14, 2023
• Last Updated: December 8, 2020

Record last verified: 2020-12