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)
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)
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.
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