Multiple Dose Study to Evaluate the Efficacy, Safety and Pharmacodynamics of REMD-477 in Subjects With Type 1 Diabetes Mellitus

• ClinicalTrials.gov Identifier: NCT03117998
• Recruitment Status: Recruiting
• First Posted: April 18, 2017
• Last Update Posted: October 14, 2020
• Sponsor: REMD Biotherapeutics, Inc.
• Information provided by (Responsible Party): REMD Biotherapeutics, Inc.

Study Description

Brief Summary:

This is a randomized, placebo-controlled, double-blind study to evaluate the efficacy, safety, and pharmacodynamics (PD) of multiple doses of REMD-477 in subjects who have Type 1 diabetes and are currently receiving insulin treatment. This study will determine whether REMD-477 can decrease daily insulin requirements and improve glycemic control after 12 weeks of treatment in subjects diagnosed with Type 1 diabetes with fasting C-peptide < 0.7 ng/mL at Screening.

The study will be conducted at multiple sites in the United States. Approximately 150 subjects with type 1 diabetes on stable doses of insulin will be randomized in a 1:1:1 fashion into one of three treatment groups.

Condition or disease	Intervention/treatment	Phase
Type1 Diabetes Mellitus	Biological: REMD-477; Biological: Placebo Comparator	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 150 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 Study to Evaluate the Efficacy, Safety, and Pharmacodynamics of Multiple Doses of REMD-477 in Subjects With Type 1 Diabetes Mellitus
• Actual Study Start Date: September 19, 2017
• Estimated Primary Completion Date: January 30, 2021
• Estimated Study Completion Date: April 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: REMD-477 Treatment A; Administered as a repeated subcutaneous (SC) doses in subjects with Type 1 Diabetes	Biological: REMD-477; Administered as repeated SC doses in subjects with Type 1 Diabetes
Experimental: REMD-477 Treatment B; Administered as a repeated SC doses in subjects with Type 1 Diabetes	Biological: REMD-477; Administered as repeated SC doses in subjects with Type 1 Diabetes
Placebo Comparator: Matching placebo; Administered as a repeated SC doses in subjects with Type 1 Diabetes	Biological: Placebo Comparator; Administered as a repeated SC doses in subjects with Type 1 Diabetes

Outcome Measures

Primary Outcome Measures :

1. Daily Insulin Use [ Time Frame: 12 weeks ]
   Change in daily insulin use from baseline at Week 12

Secondary Outcome Measures :

1. Glucose after Mixed Meal Tolerance Test (MMTT) [ Time Frame: 13 weeks ]
   Change from baseline at Week 13 in fasting glucose and glucose area under the curve (AUC) after the Mixed Meal Tolerance Test (MMTT) after repeated doses of REMD-477.
2. Continuous Glucose Monitoring (CGM) [ Time Frame: 12 weeks ]
   Change from baseline at Week 12 in average daily 24-h blood glucose as assessed by CGM after repeated doses of REMD-477.
3. Seven-Point Glucose Profile [ Time Frame: 12 weeks ]
   Change from baseline at Week 12 in the average daily 24-h blood glucose concentration as assessed by seven-point glucose profile after repeated doses of REMD-477.
4. Product of the ratio of average glucose and insulin [ Time Frame: 12 weeks ]
   The product of the ratio of average glucose (Week 12/Baseline) and ratio of average insulin use (Week 12/Baseline).
5. Adverse Events [ Time Frame: 24 weeks ]
   Number of treatment emergent adverse events per subject, including clinically relevant changes in medical history, physical examination, laboratory safety values, and ECGs
6. Hypoglycemic Events [ Time Frame: 12 weeks ]
   Incidence of hypoglycemic events, after repeated doses of REMD-477
7. HbA1c at Week 13 [ Time Frame: 13 weeks ]
   Change from baseline at Week 13 in HbA1c, after repeated doses of REMD-477.
8. HbA1c Reduction of ≥ 0.4% [ Time Frame: 12 weeks ]
   Proportion of subjects who achieve HbA1c reduction of ≥ 0.4%, after repeated doses of REMD-477
9. C-peptide after MMTT and Arginine Challenge [ Time Frame: 13 weeks ]
   Change from baseline at Week 13 in fasting C-peptide and C-peptide AUC after MMTT and arginine challenge, after repeated doses of REMD-477.
10. Glucagon after MMTT [ Time Frame: 13 weeks ]
    Change from baseline at Week 13 in peripheral levels of fasting glucagon and glucagon AUC after MMTT challenge, after repeated doses of REMD-477.
11. GLP-1 after MMTT [ Time Frame: 13 weeks ]
    Change from baseline at Week 13 in peripheral levels of active and total glucagon-like peptide 1 (GLP-1), and GLP-1 (active and total) AUC after MMTT challenge, after repeated doses of REMD-477.
12. Immunogenicity [ Time Frame: 24 weeks ]
    Incidence of REMD-477 antibody formation.
13. Peak Serum Concentration [ Time Frame: 24 weeks ]
    Maximum observed concentration (Cmax) after repeated doses of REMD-477.
14. Area under the serum concentration [ Time Frame: 24 weeks ]
    Area under the curve (AUC) serum-concentration after repeated doses of REMD-477.
15. Half-life of REMD-477 [ Time Frame: 24 weeks ]
    Half-life (t1/2) after repeated doses of REMD-477.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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. 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 32 kg/m2, inclusive, at screening;
• Diagnosed with Type 1 diabetes, based on clinical history or as defined by the current American Diabetes Association (ADA) criteria;
• HbA1c > 7% and < 10 % at screening;
• Fasting C-peptide < 0.7 ng/mL;
• Treatment with a stable insulin regimen for at least 8 weeks before screening with multiple daily insulin (MDI) injections or continue subcutaneous insulin infusion (CSII)
• Willing to use continuous CGM system (e.g. DexCom) throughout the study;
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 1.5x upper limit of normal (ULN) 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], known hemoglobinopathies, and renal dysfunction [eGFR < 60 ml/min]);
• Any severe symptomatic hypoglycemic event associated with a seizure or requiring help from other people or medical facility in the past 6 months;
• Myocardial infarction, unstable angina, revascularization procedure, or cerebrovascular accident ≤12 weeks before screening;
• History of New York Heart Association Functional Classification III-IV cardiac disease;
• Current or recent (within 1 month of screening) use of diabetes medications other than insulin - subjects on an SGLT2 inhibitor should be discontinue the SGLT2 inhibitor during the Screening Period, at least 2 weeks prior to the start of the Lead-in Period;
• 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 > 10 cigarettes/day, and/or is unwilling to abstain from smoking during admission periods;
• Known sensitivity to mammalian-derived drug preparations, recombinant protein-based drugs or to humanized or human antibodies;
• History of illicit 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 (MEN) or family history of MEN;
• History of pheochromocytoma, or family history of familial pheochromocytoma;
• Known or suspected susceptibility to infectious disease (e.g. taking immunosuppressive agents or has a documented inherited or acquired immunodeficiency);
• Known history of 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;
• Unable or unwilling to follow the study protocol or who are non-compliant with screening appointments or study visits;
• Any other condition(s) that might reduce the chance of obtaining study data, or that might cause safety concerns, or that might compromise the ability to give truly informed consent

Other inclusion and exclusion criteria may apply.

Contacts and Locations

Contacts

Contact: Dung "Zung" Thai, MD; 805-987-0600; zungthai@remdbio.com

Locations

United States, California

AMCR Institute; Recruiting

Escondido, California, United States, 92025

Contact: Timonthy S Bailey, MD 760-466-1523

Marin Endocrine Care & Research; Recruiting

Greenbrae, California, United States, 94904

Contact: Mickie Cheng, MD 415-461-1780

Altman Clinical and Translational Research Institute; Recruiting

San Diego, California, United States, 92037

Contact: Todd May 858-657-7039 tmay@ucsd.edu

Diablo Clinical Research; Recruiting

Walnut Creek, California, United States, 94598

Contact: Caitlin Sheets 925-930-7267 csheets@Diabloclinical.com

Contact: Mark Christiansen, MD

United States, Colorado

University of Colorado, Denver/Barbara Davis Center for Diabetes; Recruiting

Aurora, Colorado, United States, 80045

Contact: Halis Kaan Akturk, MD 303-724-6761 halis.akturk@ucdenver.edu

United States, Georgia

Atlanta Diabetes Assoicates; Recruiting

Atlanta, Georgia, United States, 30318

Contact: Bruce W Bode, MD 404-355-4393

United States, Missouri

Washington University School of Medicine; Recruiting

Saint Louis, Missouri, United States, 63110

Contact: Karen Flavin 314-747-8592 flavinkarens@wustl.edu

United States, Texas

Texas Diabetes & Endocrinology; Recruiting

Austin, Texas, United States, 78749

Contact: Jean Chen, MD 512-334-3505

Dallas Diabetes Research Center; Recruiting

Dallas, Texas, United States, 75230

Contact: Julio Rosenstock, MD 972-566-7799 juliorosenstock@dallasdiabetes.com

Clinical Trials of Texas; Recruiting

San Antonio, Texas, United States, 78229

Contact: Douglas S Denham, DO 210-949-0122

United States, Washington

Rainer Clinical Research Center; Recruiting

Renton, Washington, United States, 98057

Contact: Leslie Klaff, MD 425-251-1720 ljklaff@rainier-research.com

Sponsors and Collaborators

REMD Biotherapeutics, Inc.

More Information

• Responsible Party: REMD Biotherapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03117998
• Other Study ID Numbers: R477-202
• First Posted: April 18, 2017
• Last Update Posted: October 14, 2020
• Last Verified: October 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; REMD-477; Hypoglycemic Agents; Physiological Effects of Drugs