Multiple Dose Study to Evaluate the Efficacy, Safety and Pharmacodynamics of REMD-477 in Subjects With Type 1 Diabetes Mellitus
Multiple Dose Study to Evaluate the Efficacy, Safety and Pharmacodynamics of REMD-477 in Subjects With Type 1 Diabetes Mellitus
This is a randomized, placebo-controlled, double-blind study to evaluate the efficacy,
 safety, and pharmacodynamics (PD) of multiple doses of REMD-477 in subjects who have Type 1
 diabetes and are currently receiving insulin treatment. This study will determine whether
 REMD-477 can decrease daily insulin requirements and improve glycemic control after 12 weeks
 of treatment in subjects diagnosed with Type 1 diabetes with fasting C-peptide < 0.7 ng/mL at
 Screening.

 The study will be conducted at multiple sites in the United States. Approximately 150
 subjects with type 1 diabetes on stable doses of insulin will be randomized in a 1:1:1
 fashion into one of three treatment groups.
Inclusion Criteria:

 -  Men and women between the ages of 18 and 65 years old, inclusive, at the time of
 screening;

 -  Females of non-child bearing potential must be ≥1 year post-menopausal (confirmed by a
 serum follicle-stimulating hormone (FSH) levels ≥ 40 IU/mL) or documented as being
 surgically sterile. Females of child bearing potential must agree to use two methods
 of contraception;

 -  Male subjects must be willing to use clinically acceptable method of contraception
 during the entire study;

 -  Body mass index between 18.5 and 32 kg/m2, inclusive, at screening;

 -  Diagnosed with Type 1 diabetes, based on clinical history or as defined by the current
 American Diabetes Association (ADA) criteria;

 -  HbA1c > 7% and < 10 % at screening;

 -  Fasting C-peptide < 0.7 ng/mL;

 -  Treatment with a stable insulin regimen for at least 8 weeks before screening with
 multiple daily insulin (MDI) injections or continue subcutaneous insulin infusion
 (CSII)

 -  Willing to use continuous CGM system (e.g. DexCom) throughout the study;

 -  Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 1.5x upper
 limit of normal (ULN) at screening;

 -  Able to provide written informed consent approved by an Institutional Review Board
 (IRB).

 Exclusion Criteria:

 -  History or evidence of clinically-significant disorder or condition that, in the
 opinion of the Investigator, would pose a risk to subject safety or interfere with the
 study evaluation, procedures, or completion;

 -  Significant organ system dysfunction (e.g., clinically significant pulmonary or
 cardiovascular disease, anemia [Hemoglobin < 10.0 g/dL], known hemoglobinopathies, and
 renal dysfunction [eGFR < 60 ml/min]);

 -  Any severe symptomatic hypoglycemic event associated with a seizure or requiring help
 from other people or medical facility in the past 6 months;

 -  Myocardial infarction, unstable angina, revascularization procedure, or
 cerebrovascular accident ≤12 weeks before screening;

 -  History of New York Heart Association Functional Classification III-IV cardiac
 disease;

 -  Current or recent (within 1 month of screening) use of diabetes medications other than
 insulin - subjects on an SGLT2 inhibitor should be discontinue the SGLT2 inhibitor
 during the Screening Period, at least 2 weeks prior to the start of the Lead-in
 Period;

 -  Use of steroids and/or other prescribed or over-the-counter medications that are known
 to affect the outcome measures in this study or known to influence glucose metabolism;

 -  Smokes > 10 cigarettes/day, and/or is unwilling to abstain from smoking during
 admission periods;

 -  Known sensitivity to mammalian-derived drug preparations, recombinant protein-based
 drugs or to humanized or human antibodies;

 -  History of illicit drug use or alcohol abuse within the last 6 months or a positive
 drug urine test result at screening;

 -  History of pancreatitis, pancreatic neuroendocrine tumors or multiple endocrine
 neoplasia (MEN) or family history of MEN;

 -  History of pheochromocytoma, or family history of familial pheochromocytoma;

 -  Known or suspected susceptibility to infectious disease (e.g. taking immunosuppressive
 agents or has a documented inherited or acquired immunodeficiency);

 -  Known history of positive for human immunodeficiency virus (HIV) antibodies, hepatitis
 B surface antigen (HbsAg), or hepatitis C antibodies (HepC Ab);

 -  Participation in an investigational drug or device trial within 30 days of screening
 or within 5 times the half-life of the investigational agent in the other clinical
 study, if known, whichever period is longer;

 -  Blood donor or blood loss > 500 mL within 30 days of Day 1;

 -  Women who are pregnant or lactating/breastfeeding;

 -  Unable or unwilling to follow the study protocol or who are non-compliant with
 screening appointments or study visits;

 -  Any other condition(s) that might reduce the chance of obtaining study data, or that
 might cause safety concerns, or that might compromise the ability to give truly
 informed consent

 Other inclusion and exclusion criteria may apply.