consistent 1: metabolic and safety outcomes of hylenex recombinant (hyaluronidase human injection) preadministered at csii infusion site in participants with type 1 diabetes mellitus (t1dm)

Conditions: Type 1 Diabetes Mellitus

Summary: the primary objectives of this study are to compare the difference in glycosylated hemoglobin (hba1c) from baseline to month 6 using hylenex recombinant preadministration in continuous subcutaneous insulin infusion (csii) versus standard csii and to evaluate the safety of hylenex recombinant preadministration, including local tolerability, adverse events, and hypo- and hyperglycemia rates.

this phase 4 study is designed to demonstrate noninferiority of pretreatment with hylenex recombinant in the csii setting to rapid-acting analog insulin alone with respect to glycemic control as assessed by changes in hba1c in participants with type 1 diabetes mellitus. total duration of study treatment is 24 months. however, according to the study design, the primary outcome measure is to be assessed at 6 months and an interim analysis is to be completed at 6 months for the secondary outcome measures and adverse events. therefore, data reported in this clinical trials record is for the 6-month interim analysis.

Eligibility criteria:
inclusion criteria: 1. male or female of age 18 years or older with a history of t1dm for at least 12 months 2. glycosylated hemoglobin (hba1c) 6.5% to 9.5% (inclusive) based on central laboratory results 3. fasting c-peptide \<0.6 nanograms per milliliter (ng/ml) 4. current use of an insulin pump compatible with available tubing for hylenex recombinant infusion and use of an infusion set compatible with the tubing available or willingness to switch to an infusion set compatible with tubing available for infusion of hylenex recombinant 5. current treatment at the time of screening with insulin \<300 units per day (u/day) 6. participants who routinely use continuous glucose monitoring (cgm) (defined as average cgm use 5 or more days per week over the preceding 3 months) and those who do not routinely used cgm are both eligible for inclusion in the study. intermittent use of cgm is also acceptable but will not be a criterion use for stratified randomization. 7. participants should be in good general health based on medical history and physical examination, without medical conditions that might prevent the completion of study drug infusions and assessments required in this protocol. exclusion criteria: 1. type 2 diabetes 2. known or suspected allergy to any component of any of the study drugs in this study 3. severe proliferative retinopathy or maculopathy, and/or gastroparesis, and/or severe neuropathy, in particular autonomic neuropathy, of such severity as to impede the participant's ability to comply with protocol procedures, as judged by the investigator 4. history of transmural myocardial infarction, congestive heart failure and uncontrolled hypertension (diastolic blood pressure \[bp\] consistently \>100 millimeters of mercury \[mmhg\]) are exclusionary 5. as judged by the investigator, clinically significant active disease of the gastrointestinal, cardiovascular (including history of stroke, history of arrhythmia, or conduction delays on electrocardiogram \[ecg\]), hepatic, neurological, renal, genitourinary, pulmonary, or hematological systems of such severity as to impede the participant's ability to comply with protocol procedures 6. history of any illness or disease that in the opinion of the investigator might confound the results of the study or pose additional risk in administering the study drugs to the participant 7. as judged by the investigator, clinically significant findings in routine laboratory data at screening 8. use of drugs that may interfere with the interpretation of study results or are known to cause clinically relevant interference with hyaluronidase action, insulin action, glucose utilization, or recovery from hypoglycemia (including systemic pharmacologic corticosteroid). use of pramlintide or a glucagon-like peptide \[glp\]-1 receptor agonist is not exclusionary but participants using these agents will be subjected to stratified randomization. use of aspirin (acetylsalicylic acid \[asa\]) up to 325 milligrams (mg)/day is not exclusionary but should be noted for analysis. 9. hypoglycemic unawareness of such severity as to impede the participant's ability to comply with protocol procedures, as judged by the investigator. 10. current addiction to alcohol or substance abuse as determined by the investigator. 11. pregnancy, breast-feeding, the intention of becoming pregnant, or not using adequate contraceptive measures (adequate contraceptive measures consist of sterilization, intra-uterine device \[iud\], oral or injectable contraceptives, and/or barrier methods). abstinence alone is not considered an adequate contraceptive measure for the purposes of this study. 12. mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation in this study

Keywords: type 1 diabetes mellitus sub cutaneous insulin infusion rapid acting analog insulin hylenex halozyme phase 4