Diabetes Mellitus, Type 1Phase 2DAYNCT03794960
Diabetes AutoimmunitY Withdrawn in Established Patients (DAY)
A Phase 2 study testing TOL-3021 in people with Diabetes Mellitus, Type 1, run by Tolerion, Inc..
Trial summary
The study is a prospective, randomized, double-blind, placebo-controlled, multicenter trial in subjects with established T1D. Read more about this study
- Who is it for?
- Ages 12 to 36 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
- No sites listed yet
- 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 36 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 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.
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- 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.
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, 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.
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 Established Type 1 Diabetes Mellitus
The study is a prospective, randomized, double-blind, placebo-controlled, multicenter trial in subjects with established T1D.
Read the detailed description
The study will include 216 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 18-35 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.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- TOL-3021, TOL-3021 Placebo
- Keywords
- Diabetes, Type 1 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
A plasmid expression vector containing the coding sequences for full-length human proinsulin.
TOL-3021 PlaceboOther
Also called Placebo
TOL-3021 Placebo
| Study group | Role | What they receive |
|---|---|---|
| TOL-3021 | Experimental | Not described Receives: Biological: TOL-3021 |
| TOL-3021 Placebo | Placebo comparator | Not described Receives: Other: TOL-3021 Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
By glucometer, a single blood glucose level
Measured: at Week 52
Rate of Clinically important hypoglycemia as defined by measured glucose value of <54 mg/dL (3.0 mM/L)
By CGM, ≥15 consecutive minutes with glucose <54 mg/dL
Measured: at Week 52
Rate of Clinically important hypoglycemia as defined by measured glucose value of <54 mg/dL (3.0 mM/L)
Total daily insulin requirements in units per kilogram (kg) body weight
Measured: at Week 52
Rate of Clinically important hypoglycemia as defined by measured glucose value of <54 mg/dL (3.0 mM/L)
HbA1c
Measured: at Week 52
Clinical responder analysis
Proportion of subjects in each treatment arm with HbA1c levels less than 6.5% at Week 52
Measured: at Week 52
Clinical responder analysis
Measure by GMS - Time in range 70 - 80 mg/dL
Measured: at Week 52
Clinical responder analysis
Measure by GMS - Time >180 mg/dL
Measured: at Week 52
Clinical responder analysis
Measure by GMS - Time >250 mg/dL
Measured: at Week 52
Clinical responder analysis
Measure by GMS - Mean Glucose Coefficient of Variation
Measured: at Week 52
Clinical responder analysis
Measure by GMS - Low Blood Glucose Index (LBGI)
Measured: at Week 52
Clinical responder analysis
Measure by GMS - Glucose below 70 mg/dL Area Over the Curve (AOC70)
Measured: at Week 52
Other measures of hypoglycemia
Severe hypoglycemia (SH) events (impaired or loss of consciousness requiring assistance of another)
Measured: at Week 52
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
Other measures of hypoglycemia
Total time <70 mg/dL by CGM
Measured: at Week 52
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
Immunologic
Quantum dot (Q-dot) responses within the qualifying subpopulation to confirm induction of specific autoantigen tolerance
Measured: at Week 52
Immunologic
Comparison of quantum dot responses within the qualifying subpopulation to clinical outcomes to confirm correlation with specific autoantigen tolerance.
Measured: at Week 52
Immunologic
Determine effect of treatment on and predictive value of regulatory/protective humoral immune response to proinsulin/insulin
Measured: at Week 52
Immunologic
Determine effect of treatment on and predictive value of serum insulin autoantibody affinity for subjects
Measured: at Week 52
Immunologic
Determine effect of treatment on and predictive value of Insulin autoantibody isotypes (IgA and IgM) and IgG subclasses
Measured: at Week 52
Immunologic
Determine 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
Immunologic
Determine 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.
- First posted7 Jan 2019
- Study start14 Dec 2019 (estimated)
- Primary completion14 Dec 2021 (estimated)
- Study completion14 Dec 2023 (estimated)
Why it stopped: Modification to Clinical Development Plan
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tolerion, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03794960
- Sponsor's protocol ID
- TOL-3021-230
- Acronym
- DAY
- 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
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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 Established Type 1 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT03794960
- Acronym / sponsor ID
- DAY / TOL-3021-230
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- Diabetes, Type 1 Diabetes, Diabetes Mellitus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Modification to Clinical Development Plan
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Tolerion, Inc.Industry (pharma, biotech, devices)
- Study start
- 14 Dec 2019 (estimated)
- Primary completion
- 14 Dec 2021 (estimated)
- Study completion
- 14 Dec 2023 (estimated)
- First posted
- 7 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is a prospective, randomized, double-blind, placebo-controlled, multicenter trial in subjects with established T1D.
Detailed description
The study will include 216 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 18-35 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TOL-3021 | Experimental | Biological: TOL-3021 |
| TOL-3021 Placebo | Placebo comparator | Other: TOL-3021 Placebo |
Who may qualify
- Ages
- 12 to 36 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- 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.
- Presence of antibodies to at least one of the following antigens: GAD-65, IA-2, ZnT8; or insulin.
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TOL-3021A plasmid expression vector containing the coding sequences for full-length human proinsulin. | Biological | TOL-3021 |
| TOL-3021 PlaceboAlso: PlaceboTOL-3021 Placebo | Other | TOL-3021 Placebo |
Primary outcome
Treatment Effect
Time frame: at Week 52
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
22 secondary outcomes
Rate of Clinically important hypoglycemia as defined by measured glucose value of <54 mg/dL (3.0 mM/L)
Time frame: at Week 52
Rate of Clinically important hypoglycemia as defined by measured glucose value of <54 mg/dL (3.0 mM/L)
Time frame: at Week 52
Rate of Clinically important hypoglycemia as defined by measured glucose value of <54 mg/dL (3.0 mM/L)
Time frame: at Week 52
Rate of Clinically important hypoglycemia as defined by measured glucose value of <54 mg/dL (3.0 mM/L)
Time frame: at Week 52
Clinical responder analysis
Time frame: at Week 52
Clinical responder analysis
Time frame: at Week 52
Clinical responder analysis
Time frame: at Week 52
Clinical responder analysis
Time frame: at Week 52
Clinical responder analysis
Time frame: at Week 52
Clinical responder analysis
Time frame: at Week 52
Clinical responder analysis
Time frame: at Week 52
Other measures of hypoglycemia
Time frame: at Week 52
Other measures of hypoglycemia
Time frame: at Week 52
Other measures of hypoglycemia
Time frame: at Week 52
Other measures of hypoglycemia
Time frame: at Week 52
Immunologic
Time frame: at Week 52
Immunologic
Time frame: at Week 52
Immunologic
Time frame: at Week 52
Immunologic
Time frame: at Week 52
Immunologic
Time frame: at Week 52
Immunologic
Time frame: at Week 52
Immunologic
Time frame: at Week 52
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2020.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
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..
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 10 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.
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 (time frame: at Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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.