MER3101: MAS-1 Adjuvanted Antigen-specific Immunotherapeutic for Prevention and Treatment of Type 1 Diabetes

The study is a four-arm (cohort), single center, randomized, double-masked, placebo-controlled, dose-escalation clinical trial. In this Phase I study, subjects (5 active MER3101 per arm plus 2 MAS-1 placebo) will be randomized to receive two intramuscular doses at days 0 and 28 of either MAS-1 placebo emulsion or MAS-1 adjuvanted IBC at 33, 109, and 327 µg IBC in 0.25 mL MAS-1 adjuvanted emulsion, followed by an additional arm to receive the optimal IBC dose selected from the first 3 arms in 0.25 mL MAS-1 emulsion. All groups will receive standard intensive diabetes treatment with insulin and dietary management.

The primary endpoint is assess the safety and tolerability of 3 doses of progressively higher IBC antigen doses of the vaccine, at 0.25 mL of MAS-1 adjuvant emulsion. In addition, to determine if the vaccine induces a shift towards protection shown by increased levels of IL-4, IL-5, IL-10 and TGF-b and regulatory changes in insulin-specific T and B cells using novel reagents to detect these unique populations of cells in treated subjects.

Inclusion criteria

• Be between the ages of 18 and 45 years of age who meet the ADA standard T1DM criteria and are positive for at least 1 islet cell autoantibody.
• Type 1-diabetes mellitus diagnosed within the previous 2 years at time of screening
• Must have stimulated C-peptide levels ≥ 0.2 pmol/ml measured during a mixed meal tolerance test (MMTT) conducted at least 21 days from diagnosis of diabetes and within one month (37 days) of randomization
• At least one month from last immunization
• Must be willing to comply with intensive diabetes management
• If participant is female with reproductive potential, she must have a negative pregnancy test and be willing to avoid pregnancy during the treatment period until 2 months after the last study drug administration.
• Willing to forgo routine clinical immunizations during the first 100 days after initial study drug administration (COVID-19 vaccination is permitted 60 days following initial study drug administration)
• Subjects must have HbA1c levels under 9.5 to be enrolled in the study.
• At least 30 days from receiving a single dose COVID-19 vaccine or at least 30 days from completing a multi-dose COVID-19 vaccine series.

Exclusion criteria

• Be currently pregnant or lactating, or anticipate getting pregnant during the treatment period until 2 months after the last study drug administration.
• Ongoing use of medications known to influence glucose tolerance
• Require use of systemic immunosuppressant(s)
• Any significant diabetes complications such as renal disease (proteinuria or elevated Cr) and diabetic retinopathy
• Have a history of malignancies
• Be currently using non-insulin pharmaceuticals to affect glycemic control
• Have any acute or chronic complicating medical issues or abnormal clinical laboratory results that interfere with study conduct or cause increased risk including neurological abnormalities.
• Inability or unwillingness to comply with the provisions of this protocol
• Have an active infection or positive tuberculosis test result.
• Have serologic evidence of current or past HIV, Hep B, or Hep C infection.
• Have a known history of hypersensitivity or allergy reactions to squalane or squalene based adjuvants or other components of the study immunogen
• Subjects with a history or evidence of chronic kidney disease (serum creatinine> 1.5mg/dL)
• Subjects with a history of proliferative diabetic retinopathy that has not been treated with laser therapy
• Subjects with a history of neuropathy, foot ulcers, amputations, or kidney disease
• Males of reproductive potential who are unwilling to use acceptable birth control during the treatment period through 2 months after the last study drug administration, unless the female partner is postmenopausal or surgically sterile.
• Have current, confirmed COVID-19 infection