Diabetes, Type 1 Diabetes Mellitus
Conditions
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.
Interventions
BIOLOGICALREMD-477
BIOLOGICALPlacebo Comparator
Sponsors
REMD Biotherapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of treatment emergent adverse events per subject, including changes in vital signs, physical and neurological examinations, laboratory safety tests and ECGs | Baseline and 57 days |
| 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. | Baseline (24 hour period on Day 1) and Days 3 and 4 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes from baseline over time of ALT. | Baseline and 57 days | Incidence of elevated serum alanine transaminase (ALT) values \>3x the upper limit of normal (ULN). |
| Changes from baseline over time of ALP. | Baseline and 57 days | Incidence of elevated serum alkaline phosphatase (ALP) \>2x upper limit of normal (ULN) |
| Immunogenicity: Incidence of REMD-477 neutralizing and non-neutralizing antibodies | Baseline and 57 days | — |
| Changes from baseline over time of amylase | Baseline and 57 days | Incidence of elevated serum amylase values at \>2.5x ULN |
| Changes from baseline over time of lipase | Baseline and 57 days | Incidence of elevated serum lipase values at \>2.5x ULN |
| Changes from baseline over time of total bilirubin. | Baseline and 57 days | Incidence of elevated serum total bilirubin \>2x upper limit of normal (ULN). |
| Changes from baseline over time of AST. | Baseline and 57 days | Incidence of elevated serum aspartate transaminase (AST) values \> 3x the upper limit of normal (ULN). |
Countries
United States
Outcome results
None listed