TrialNet TOPPLE

Clinical Study Details

Title

TrialNet- TOPPLE

Description

This is a Phase 1 study to assess the assess safety and tolerability of a DNA plasmid (see the two page summary  in the right column for more details). The plasmid is designed to halt the immune attack on the insulin producing beta cells. The study involves 12 subcutaneous weekly injections with follow up for a year after the initial dose.

The first dose of the plasmid will be given in the hospital where you would be followed for 48 hours as an inpatient. Each of the following 11 weekly doses would be at the Stanford clinical research center. Because of this, you need to live in the San Francisco Bay area. We will continue to follow you for 12 months overall.

This is a randomized, placebo controlled, dose-finding (first in humans) study where every 9 out of 12 subjects will get some dose level of the plasmid. The primary purpose of the study is to assess the safety of the plasmid in humans by the number of adverse events (side effects) experienced across all subjects. The study also uses a mixed meal tolerance test to measure beta cell function through C-peptide levels of insulin production). There is some financial compensation provided for visits to our Clinical Trial Research Unit.

Many more details, including a two page summary, the study consent form, and the volunteer handbook, can be downloaded from the colum on the right. 

You may also find more study details listed on clinicaltrials.gov with the identifier of NCT04279613

Inclusion Criteria

  1. Willing to provide Informed Consent
  2. Participants must live in a location with rapid access to emergency medical services
  3. Age 18-45 years (both inclusive) at the time of signing informed consent
  4. Must have a diagnosis of T1D for less than 48 months at randomization
  5. Must have at least one diabetes-related autoantibody present (GAD65A; mIAA, if obtained within 10 days of the onset of insulin therapy; IA-2A; ICA; or ZnT8A)
  6. Must have stimulated C-peptide levels greater than or equal to 0.2 pmol/ml measured during an MMTT conducted at least 21 days from diagnosis of diabetes and within one month (37 days) of randomization
  7. Be willing to comply with intensive diabetes management
  8. HbA1c ≤8.5% at screening
  9. Subjects who are CMV and/or EBV seronegative at screening must be CMV and/or EBV PCR negative within 30 days of randomization and may not have had signs or symptoms of a CMV and/or EBV compatible illness lasting longer than 7 days within 30 days of randomization
  10. Be up to date on recommended immunizations
  11. Be at least 6 weeks from last live immunization
  12. Be at least 4 weeks from killed vaccine other than flu vaccine
  13. Participants are required to receive killed influenza vaccination at least 2 weeks prior to randomization when vaccine for the current or upcoming flu season is available
  14. Be willing and medically acceptable to postpone live vaccines during the treatment period and for 3 months following last dose of study drug
  15. If participant is female with reproductive potential, she must have a negative pregnancy test at screening and be willing to avoid pregnancy using a highly effective contraceptive method for the 12 months of the study
  16. Males of reproductive age must use adequate contraceptive method during the treatment phase and for 3 months following last dose of study drug

Exclusion Criteria

  1. One or more screening laboratory values as stated

    1. Leukocytes < 3,000/μL
    2. Neutrophils <1,500 /μL
    3. Lymphocytes <800 /μL
    4. Platelets <100,000 /μL
    5. Haemoglobin <6.2 mmol/L (10.0 g/dL)
    6. Potassium >5.5 mmol/L or <3.0 mmol/L
    7. Sodium >150mmol/L or < 130mmol/L
    8. AST or ALT ≥2.5 times the upper limits of normal
    9. Bilirubin ≥ 1.5 times upper limit of normal
    10. Glomerular Filtration Rate (eGFR) value of eGFR < 60 ml/min/1.73 m2 as defined by KDIGO 2012 (43)
    11. Any other laboratory abnormality that might, in the judgment of the investigator, place the subject at unacceptable risk for participation in this trial
  2. Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within prior 7 days of screening
  3. Use of other immunosuppressive agents including chronic use of systemic steroids. Topical products are acceptable (nasal, conjunctival, skin)
  4. Have active signs or symptoms of acute infection at the time of randomization
  5. Have current, confirmed COVID-19 infection
  6. Chronic active infection other than localized skin infections
  7. Have evidence of prior or current tuberculosis infection as assessed by PPD, interferon gamma release assay or by history
  8. Have evidence of current or past HIV, Hepatitis B infection
  9. Have evidence of active Hepatitis C infection
  10. Vaccination with a live virus within the last 6 weeks and killed vaccine within 4 weeks (except 2 weeks for flu vaccine)
  11. Be currently pregnant or lactating, or anticipate getting pregnant within the one-year study period.
  12. Have severe obesity: adults BMI ≥ 40
  13. Have a history of malignancies
  14. Untreated hypothyroidism or active Graves' disease
  15. History of severe reaction to prior vaccination
  16. Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days after last blood draw (or 5 half-lives of investigational drug, whichever is greater) before screening, or currently enrolled in any other clinical trial
  17. Subject is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the trial
  18. Supine blood pressure at screening outside the range of 90-139 mmHg for systolic or 50-89 mmHg for diastolic. To exclude white-coat nervousness a single repeat measurement is allowed
  19. Have any complicating medical issues or abnormal clinical laboratory results that may interfere with study conduct, or cause increased risk
  20. Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results

More Info

If you're interested in learning more about this study, please reach out to the research coordinator listed on the right. You may also download the consent form, assent form, and any other documents linked on the right.


Study Contact

Karen Barahona

karenbb@stanford.edu