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

NCT ID: NCT03117998

Last Updated: 2023-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 154 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-19
• Study Completion Date: 2021-03-05

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.

Conditions

Type1 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

35 mg REMD-477

Administered as a repeated subcutaneous (SC) doses in subjects with Type 1 Diabetes

Group Type: EXPERIMENTAL

REMD-477

Intervention Type: BIOLOGICAL

Administered as repeated SC doses in subjects with Type 1 Diabetes

70 mg REMD-477

Administered as a repeated SC doses in subjects with Type 1 Diabetes

Group Type: EXPERIMENTAL

REMD-477

Intervention Type: BIOLOGICAL

Administered as repeated SC doses in subjects with Type 1 Diabetes

Matching placebo

Administered as a repeated SC doses in subjects with Type 1 Diabetes

Group Type: PLACEBO_COMPARATOR

Placebo Comparator

Intervention Type: BIOLOGICAL

Administered as a repeated SC doses in subjects with Type 1 Diabetes

Interventions

REMD-477

Administered as repeated SC doses in subjects with Type 1 Diabetes

Intervention Type: BIOLOGICAL

Placebo Comparator

Administered as a repeated SC doses in subjects with Type 1 Diabetes

Intervention Type: BIOLOGICAL

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

REMD Biotherapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

AMCR Institute

Escondido, California, United States

Marin Endocrine Care & Research

Greenbrae, California, United States

Altman Clinical and Translational Research Institute

San Diego, California, United States

Diablo Clinical Research

Walnut Creek, California, United States

University of Colorado, Denver/Barbara Davis Center for Diabetes

Aurora, Colorado, United States

Atlanta Diabetes Assoicates

Atlanta, Georgia, United States

Washington University School of Medicine

St Louis, Missouri, United States

Texas Diabetes & Endocrinology

Austin, Texas, United States

Dallas Diabetes Research Center

Dallas, Texas, United States

Clinical Trials of Texas

San Antonio, Texas, United States

Rainer Clinical Research Center

Renton, Washington, United States

Countries

United States

References

Santiago Padilla L, Schiattarella GG. Targeting HFpEF: Unlocking the Potential of Glucagon Receptor Blockade. Circ Res. 2024 Aug 16;135(5):629-631. doi: 10.1161/CIRCRESAHA.124.325130. Epub 2024 Aug 15. No abstract available.

Reference Type: DERIVED

PMID: 39146397 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

R477-202

Identifier Type: -

Identifier Source: org_study_id