Single-dose Study to Evaluate Safety, Tolerability, and Pharmacodynamics of REMD-477 in Subjects With Type 1 Diabetes Mellitus

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: January 2017

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

  • Biological: REMD-477
  • Biological: Placebo Comparator

Arms, Groups and Cohorts

  • Experimental: REMD-477 Treatment A
    • Administered as a single SC dose in subjects with Type 1 Diabetes
  • Placebo Comparator: Matching placebo
    • Administered as a single SC dose in subjects with Type 1 Diabetes

Clinical Trial Outcome Measures

Primary Measures

  • 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
  • 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

Secondary Measures

  • Immunogenicity: Incidence of REMD-477 neutralizing and non-neutralizing antibodies
    • Time Frame: Baseline and 57 days
  • Changes from baseline over time of AST.
    • Time Frame: Baseline and 57 days
    • Incidence of elevated serum aspartate transaminase (AST) values > 3x the upper limit of normal (ULN).
  • Changes from baseline over time of ALT.
    • Time Frame: 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.
    • Time Frame: Baseline and 57 days
    • Incidence of elevated serum alkaline phosphatase (ALP) >2x upper limit of normal (ULN)
  • Changes from baseline over time of total bilirubin.
    • Time Frame: Baseline and 57 days
    • Incidence of elevated serum total bilirubin >2x upper limit of normal (ULN).
  • Changes from baseline over time of amylase
    • Time Frame: Baseline and 57 days
    • Incidence of elevated serum amylase values at >2.5x ULN
  • Changes from baseline over time of lipase
    • Time Frame: Baseline and 57 days
    • Incidence of elevated serum lipase values at >2.5x ULN

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 60 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • REMD Biotherapeutics, Inc.
  • Provider of Information About this Clinical Study
    • Sponsor

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