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

REMD Biotherapeutics

Status and phase: Completed; Phase 2

Conditions: Type1 Diabetes Mellitus

Treatments: Biological: REMD-477; Biological: Placebo Comparator

Study type: Interventional

Funder types: Industry

Identifiers

NCT03117998

R477-202

Details and patient eligibility

About

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.

Enrollment: 154 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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154 participants in 3 patient groups, including a placebo group

35 mg REMD-477

Experimental group

Description:

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

Treatment:

Biological: REMD-477

70 mg REMD-477

Experimental group

Description:

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

Treatment:

Biological: REMD-477

Matching placebo

Placebo Comparator group

Description:

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

Treatment:

Biological: Placebo Comparator