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

February 6, 2017 updated by: REMD Biotherapeutics, Inc.

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Diego, California, United States
    • Missouri
      • St. Louis, Missouri, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome 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
Time Frame: Baseline and 57 days
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
Baseline (24 hour period on Day 1) and Days 3 and 4

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immunogenicity: Incidence of REMD-477 neutralizing and non-neutralizing antibodies
Time Frame: Baseline and 57 days
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).
Baseline and 57 days
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).
Baseline and 57 days
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)
Baseline and 57 days
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).
Baseline and 57 days
Changes from baseline over time of amylase
Time Frame: Baseline and 57 days
Incidence of elevated serum amylase values at >2.5x ULN
Baseline and 57 days
Changes from baseline over time of lipase
Time Frame: Baseline and 57 days
Incidence of elevated serum lipase values at >2.5x ULN
Baseline and 57 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

REMD Biotherapeutics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2016

Primary Completion (Actual)

January 1, 2017

Study Completion (Actual)

January 1, 2017

Study Registration Dates

First Submitted

February 29, 2016

First Submitted That Met QC Criteria

March 16, 2016

First Posted (Estimate)

March 22, 2016

Study Record Updates

Last Update Posted (Estimate)

February 7, 2017

Last Update Submitted That Met QC Criteria

February 6, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R477-101

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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