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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02715193
Recruitment Status : Completed
First Posted : March 22, 2016
Last Update Posted : February 7, 2017
Information provided by (Responsible Party):
REMD Biotherapeutics, Inc.

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.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Diabetes Biological: REMD-477 Biological: Placebo Comparator Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 2016
Actual Primary Completion Date : January 2017
Actual Study Completion Date : January 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Experimental: REMD-477 Treatment A
Administered as a single SC dose in subjects with Type 1 Diabetes
Biological: REMD-477
Placebo Comparator: Matching placebo
Administered as a single SC dose in subjects with Type 1 Diabetes
Biological: Placebo Comparator

Primary Outcome Measures :
  1. 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 ]
  2. 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 Outcome Measures :
  1. Immunogenicity: Incidence of REMD-477 neutralizing and non-neutralizing antibodies [ Time Frame: Baseline and 57 days ]
  2. 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).

  3. 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).

  4. 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)

  5. 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).

  6. Changes from baseline over time of amylase [ Time Frame: Baseline and 57 days ]
    Incidence of elevated serum amylase values at >2.5x ULN

  7. Changes from baseline over time of lipase [ Time Frame: Baseline and 57 days ]
    Incidence of elevated serum lipase values at >2.5x ULN

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts 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 exclusion criteria may apply.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02715193

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United States, California
San Diego, California, United States
United States, Missouri
St. Louis, Missouri, United States
Sponsors and Collaborators
REMD Biotherapeutics, Inc.
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: REMD Biotherapeutics, Inc. Identifier: NCT02715193    
Other Study ID Numbers: R477-101
First Posted: March 22, 2016    Key Record Dates
Last Update Posted: February 7, 2017
Last Verified: February 2017
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs