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

NCT03117998 | Completed Phase 2 Results FDA Drug

• 1 other identifier: R477-202
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 11

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

Outcome Measures

Primary Outcomes (1)

• Change in Average Daily Total Insulin Use

  Change from Baseline in average daily total insulin use at Week 12

  Baseline and 12 weeks

Secondary Outcomes (16)

• Change From Baseline Difference in AUC Glucose Concentrations Following Mixed Meal Tolerance Test (MMTT) - Part A Only

  Baseline and 13 weeks; AUC glucose timepoints: 10 minutes prior and just before (time ) initiating the mixed-meal ingestion and at 30, 60 and 120 minutes after the mixed meal ingestion.

• Continuous Glucose Monitoring (CGM) - Change in Average Daily 24-hour Glucose Concentration at Week 12

  Baseline and 12 weeks

• Seven-Point Glucose Profile - Change in Average 24-h Glucose Concentrations

  Baseline and 12 weeks

• Summary of the Product of Average Daily 24-h Glucose Ratio and Daily Insulin Use Ratio (Day 78 [Week 12]/Baseline)

  Baseline and week 12

• Change in Hemoglobin A1c From Baseline at Week 13

  Baseline and 13 weeks

Study Arms (3)

35 mg REMD-477

EXPERIMENTAL

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

Biological: REMD-477

70 mg REMD-477

EXPERIMENTAL

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

Biological: REMD-477

Matching placebo

PLACEBO COMPARATOR

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

Biological: Placebo Comparator

Interventions

REMD-477 BIOLOGICAL

Administered as repeated SC doses in subjects with Type 1 Diabetes

35 mg REMD-477; 70 mg REMD-477

Placebo Comparator BIOLOGICAL

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

Matching placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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;

Sponsors & Collaborators

• REMD Biotherapeutics, Inc.: lead

Study Sites (11)

AMCR Institute

Escondido, California, 92025, United States

Location

Marin Endocrine Care & Research

Greenbrae, California, 94904, United States

Location

Altman Clinical and Translational Research Institute

San Diego, California, 92037, United States

Location

Diablo Clinical Research

Walnut Creek, California, 94598, United States

Location

University of Colorado, Denver/Barbara Davis Center for Diabetes

Aurora, Colorado, 80045, United States

Location

Atlanta Diabetes Assoicates

Atlanta, Georgia, 30318, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Texas Diabetes & Endocrinology

Austin, Texas, 78749, United States

Location

Dallas Diabetes Research Center

Dallas, Texas, 75230, United States

Location

Clinical Trials of Texas

San Antonio, Texas, 78229, United States

Location

Rainer Clinical Research Center

Renton, Washington, 98057, United States

Location

Related Publications (1)

• 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.

  PMID: 39146397 DERIVED

MeSH Terms

Interventions

volagidemab

Results Point of Contact

• Title: Dung "Zung" Thai, MD, PhD
• Organization: REMD Biotherapeutics, Inc

zungthai@remdbio.com

415-225-9338

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2017
• First Posted: April 18, 2017
• Study Start: September 19, 2017
• Primary Completion: March 5, 2021
• Study Completion: March 5, 2021
• Last Updated: May 25, 2023
• Results First Posted: May 25, 2023

Record last verified: 2023-05

Locations

US (11)