A Randomized, Placebo-controlled, Double-blind, In-patient Study to Evaluate Safety, Tolerability, and Pharmacodynamics of REMD-477 Following a Single Dose in Subjects With Type 1 Diabetes Mellitus
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Type 1 Diabetes Mellitus
- Sponsor
- REMD Biotherapeutics, Inc.
- Enrollment
- 21
- Primary Endpoint
- Changes from baseline in 24-hour insulin requirements on Day 1 relative to the two 24 hour periods post-treatment on Days 3 and 4, between the REMD-477 and placebo treated subjects, needed to maintain targeted glycemic control.
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
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;
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;
Outcomes
Primary Outcomes
Changes from baseline in 24-hour insulin requirements on Day 1 relative to the two 24 hour periods post-treatment on Days 3 and 4, between the REMD-477 and placebo treated subjects, needed to maintain targeted glycemic control.
Time Frame: Baseline (24 hour period on Day 1) and Days 3 and 4
Number of treatment emergent adverse events per subject, including changes in vital signs, physical and neurological examinations, laboratory safety tests and ECGs
Time Frame: Baseline and 57 days
Secondary Outcomes
- Changes from baseline over time of ALT.(Baseline and 57 days)
- Changes from baseline over time of amylase(Baseline and 57 days)
- Immunogenicity: Incidence of REMD-477 neutralizing and non-neutralizing antibodies(Baseline and 57 days)
- Changes from baseline over time of AST.(Baseline and 57 days)
- Changes from baseline over time of ALP.(Baseline and 57 days)
- Changes from baseline over time of lipase(Baseline and 57 days)
- Changes from baseline over time of total bilirubin.(Baseline and 57 days)