Multiple Dose Study to Evaluate the Efficacy, Safety and Pharmacodynamics of REMD-477 in Subjects With Type 1 Diabetes Mellitus
Condition: Type1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: REMD-477; Placebo Comparator
Intervention description: Administered as repeated SC doses in subjects with Type 1 Diabetes; Administered as a repeated SC doses in subjects with Type 1 Diabetes
Intervention MeSH terms: Volagidemab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 154.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

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.
    

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

        Other inclusion and exclusion criteria may apply.