Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of REMD-477 in Subjects With Type 2 Diabetes Mellitus

Overview

This is a randomized, placebo-controlled, double-blind, dose escalation study to evaluate safety, tolerability, PK and PD of single and repeated SC doses of REMD-477 in Type 2 diabetic subjects. The study will be conducted at multiple sites in the United States and will enroll approximately 102 subjects with Type 2 diabetes who are either treatment-naïve, controlled with diet and exercise or treated with oral antidiabetic medications.

Full Title of Study: “A Randomized, Placebo-controlled, Double-blind, Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Single and Repeated Subcutaneous (SC) Doses of REMD-477 in Subjects With Type 2 Diabetes Mellitus”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: January 2018

Detailed Description

The study will consist of three parts: Part A – Dose Escalation, Part B – Adaptive Dose Cohort, and Part C – REMD-477 in Combination with Metformin. Part A includes 5 cohorts that will be enrolled and dosed sequentially at escalating doses. Each cohort will consist of 12 subjects randomized in a 3:1 (active: placebo) fashion. Part B includes a single dose cohort that will enroll 12 subjects (9 on active treatment and 3 on placebo) with dose level and frequency determined by a Dose Level Review Meeting (DLRM)Committee. Part C includes 2 cohorts of T2DM patients currently treated with metformin alone, and each cohort will consist of 15 subjects (10 on active treatment and 3 on placebo).

Interventions

  • Biological: REMD-477

Arms, Groups and Cohorts

  • Experimental: REMD-477 Treatment A
    • Administered as a single and repeated SC doses in subjects with Type 2 Diabetes
  • Placebo Comparator: Matching placebo
    • Placebo administered as single and repeated SC doses in subjects with Type 2 Diabetes
  • Experimental: REMD-477 Treatment B
    • Administered as a single and repeated SC doses in subjects with Type 2 Diabetes
  • Experimental: REMD-477 Treatment C
    • Administered as a single and repeated SC doses in subjects with Type 2 Diabetes
  • Experimental: REMD-477 Treatment D
    • Administered as a single and repeated SC doses in subjects with Type 2 Diabetes
  • Experimental: REMD-477 Treatment E
    • Administered as a single and repeated SC doses in subjects with Type 2 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: 141 Days

Secondary Measures

  • Pharmacokinetic (PK) profile (parameters including maximum observed concentration (Cmax), area under the curve (AUC) serum-concentration, clearance, and half-life (t1/2) after single and repeated SC doses.
    • Time Frame: 141 Days
  • Changes in fasting glucose and insulin levels following single and repeated SC doses of REMD-477.
    • Time Frame: 141 Days
  • Changes in glucose and insulin AUC following a Mixed Meal Tolerance Test.
    • Time Frame: Day 29, Day 57 and Day 85
  • Incidence of REMD-477 neutralizing and non-neutralizing antibodies
    • Time Frame: 141 Days
  • Incidence of elevated alanine transaminase (ALT) or aspartate transaminase (AST) values >3x the upper limit of normal with concomitant >2x increases in alkaline phosphatase (ALP) and/or >2x total bilirubin.
    • Time Frame: 141 Days
  • Incidence and severity of elevated amylase and lipase values at >2.5x ULN after study treatment
    • Time Frame: 141 Days
  • Geometric mean ratio to baseline over time of AST, ALT, ALP and total bilirubin.
    • Time Frame: 141

Participating in This Clinical Trial

Inclusion Criteria

  • Men and women between the ages of 18 and 65 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, and females of child bearing potential must use two medically acceptable methods of contraception; – Male subjects must be willing to use clinically acceptable contraception during treatment and for 2 months after the last administration of REMD-477; – Normal or clinically-acceptable physical examination, laboratory test values, and 12-lead ECG (reporting heart rate and PR, QRS, QT, and QTcF) at screening; – Body mass index between 23 and 40 kg/m2, inclusive, at screening; – Diagnosed with Type 2 diabetes as defined by the current American Diabetes Association (ADA) criteria; – Subjects in Parts A and B only: Treatment-naive, controlled with diet and exercise, or treated with oral antidiabetic medications and willing to wash-out and discontinue oral medications during the study; – Fasting plasma glucose 126 – 270 mg/dL (7-15 mM), inclusive, at screening and at re-test on Day -1; – Subjects in Parts A and B only: Screening HbA1c of 7.0-10 % inclusive for subjects not currently taking any oral antidiabetic medications, or 6.5-9.5% for subjects receiving acceptable oral antidiabetic medications; – Subjects in Part C only: Screening HbA1c of 7.5-10 % inclusive for subjects on stable doses of metformin. Exclusion Criteria:

  • History of drug or alcohol abuse within the last 6 months or a positive illegal drug urine test result; – History or family history of pancreatic neuroendocrine tumors or multiple endocrine neoplasia; – History or family history of 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>300 mL, within 30 days of Day 1; – Recent use (6 weeks prior to Screening) of thiazolidinediones, >half-maximal dose sulfonylurea agent therapy, or any injectable antidiabetic agents (exenatide and other injectable GLP-1 agonists, insulin and insulin analogs, etc.); – Other gastrointestinal, cardiac, renal and CNS (i.e. hypoglycemia unawareness) conditions specific to diabetes that would pose additional risk to subject's safety or interfere with the study evaluation, procedures or completion; – Lipid panel profiles of non-HDL-C (total cholesterol minus HDL-C) >219 mg/dL, LDL-C >189 mg/dL, and/or fasting triglycerides >499 mg/dL; – Female subject is pregnant or breastfeeding. Other inclusion and exclusion criteria may apply.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 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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