Single-dose Study to Evaluate Safety, Tolerability, and Pharmacodynamics of REMD-477 in Subjects With Type 1 Diabetes Mellitus
Single-dose Study to Evaluate Safety, Tolerability, and Pharmacodynamics of REMD-477 in Subjects With Type 1 Diabetes Mellitus
This is a randomized, placebo-controlled, double-blind study to evaluate safety, tolerability
 and pharmacodynamics of REMD-477 in subjects who have Type 1 diabetes and are currently
 receiving insulin treatment. This proof of concept study will determine whether glucagon
 receptor blockade using a single dose REMD-477 can improve short-term glucose homeostasis in
 people with Type 1 diabetes.
The study will be conducted at two sites in the United States, and approximately 20 subjects
 with type 1 diabetes will be enrolled. Eligible subjects will be admitted to the clinical
 research unit, to carefully monitor blood glucose; and establish the baseline insulin
 requirement for maintaining targeted normoglycemia (postabsorptive: 90-120 mg/dL; and
 postprandial: <180 mg/dL).

 The patients will then be subjected to a hyperglycemic period (250-300 mg/dL) by a stepwise
 reduction in insulin infusion. After receiving a single SC dose of REMD-477 or matching
 placebo in a double-blinded fashion, all subjects will be assessed for the post-treatment
 24-hour insulin requirement needed to maintain targeted normoglycemia (postabsorptive: 90-120
 mg/dL; and postprandial: <180 mg/dL); and to be monitored closely for safety, tolerability
 and targeted glycemic control, for a 48-hr period. After the in-patient residency period,
 subjects will return to the clinic for weekly out-patient safety follow-up visits for 8
 weeks.
Inclusion Criteria:

 -  Men and women between the ages of 18 and 60 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 26.9 kg/m2, inclusive, at screening;

 -  Diagnosed with Type 1 diabetes for greater than 2 years, based on clinical history or
 as defined by the current American Diabetes Association (ADA) criteria;

 -  HbA1c ≥6.0 % but <9.0 % at screening;

 -  Fasting C-peptide <0.2 ng/mL;

 -  Current use of insulin pump and willing to use continuous glucose monitoring (CGM)
 system (e.g. DexCom) throughout the entire study;

 -  ALT and/or AST within <1.5x ULN at screening;

 -  Serum amylase and lipase within normal limits 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], and renal dysfunction [eGFR
 <90 ml/1.73M2/min]);

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

 -  Current or recent (within 1 month of screening) use of diabetes medications other than
 insulin;

 -  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 tobacco;

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

 -  History of illegal 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;

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

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

 -  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;

 -  Regular exercise >120 min/week within 14 days of Day 1;

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

 -  Family history of multiple endocrine neoplasia.

 Other inclusion and exclusion criteria may apply.