Single-dose Study to Evaluate Safety, Tolerability, and Pharmacodynamics of REMD-477 in Subjects With Type 1 Diabetes Mellitus
Study Details
Study Description
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 |
|---|---|---|
|
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.
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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]
Incidence of elevated serum aspartate transaminase (AST) values > 3x the upper limit of normal (ULN).
- 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)
- 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 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
Eligibility Criteria
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;
-
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;
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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;
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Blood donor or blood loss >500 mL within 30 days of Day 1;
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Women who are pregnant or lactating/breastfeeding;
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Regular exercise >120 min/week within 14 days of Day 1;
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | San Diego | California | United States | ||
| 2 | St. Louis | Missouri | United States |
Sponsors and Collaborators
- REMD Biotherapeutics, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- R477-101