Overview

This trial is active, not recruiting.

Condition type 1 diabetes mellitus
Treatments commercial hylenex® recombinant (hyaluronidase human injection), pre-commercial formulation of hylenex recombinant (hyaluronidase human injection), preadministration of commercial hylenex® recombinant (hyaluronidase human injection), preadministration of pre-commercial hylenex recombinant (hyaluronidase human injection), continuous subcutaneous insulin infusion (csii) via insulin infusion pumps
Phase phase 4
Sponsor Halozyme Therapeutics
Start date March 2013
End date January 2014
Trial size 400 participants
Trial identifier NCT01848990, Halo-117-403

Summary

The primary objectives of this study are to compare the difference in A1C from baseline to month 4 using Hylenex recombinant preadministration in CSII versus standard CSII and to evaluate the safety of Hylenex recombinant preadministration, including local tolerability, immunogenicity, adverse events and hypo- and hyperglycemia rates.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model factorial assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Preadministration of commercial Hylenex® recombinant (Formulation 1) delivered as a pretreatment each time an infusion set is deployed for the full 24 month duration of the study.
commercial hylenex® recombinant (hyaluronidase human injection) Commercial Hylenex® recombinant
See Arm Description
preadministration of commercial hylenex® recombinant (hyaluronidase human injection)
See Arm Description
continuous subcutaneous insulin infusion (csii) via insulin infusion pumps
Continuous Subcutaneous Insulin Infusion (CSII) via insulin infusion pumps of varying manufacturers.
(Active Comparator)
Preadministration of a pre-commercial formulation (Formulation 2) of Hylenex recombinant delivered as a pretreatment each time an infusion set is deployed for the full 24 month duration of the study.
pre-commercial formulation of hylenex recombinant (hyaluronidase human injection) Formulation 2
See Arm Description
preadministration of pre-commercial hylenex recombinant (hyaluronidase human injection)
See Arm Description
continuous subcutaneous insulin infusion (csii) via insulin infusion pumps
Continuous Subcutaneous Insulin Infusion (CSII) via insulin infusion pumps of varying manufacturers.
(Active Comparator)
CSII treatment using commercial Hylenex® recombinant (Formulation 1) pretreatment each time an infusion set is deployed for the first 12 months followed by crossover to standard CSII treatment for the next 12 months
commercial hylenex® recombinant (hyaluronidase human injection) Commercial Hylenex® recombinant
See Arm Description
preadministration of commercial hylenex® recombinant (hyaluronidase human injection)
See Arm Description
continuous subcutaneous insulin infusion (csii) via insulin infusion pumps
Continuous Subcutaneous Insulin Infusion (CSII) via insulin infusion pumps of varying manufacturers.
(Active Comparator)
Standard CSII treatment for the first 12 months followed by crossover to commercial Hylenex® recombinant (Formulation 1) pretreatment each time an infusion set is deployed for the next 12 months
commercial hylenex® recombinant (hyaluronidase human injection) Commercial Hylenex® recombinant
See Arm Description
preadministration of commercial hylenex® recombinant (hyaluronidase human injection)
See Arm Description
continuous subcutaneous insulin infusion (csii) via insulin infusion pumps
Continuous Subcutaneous Insulin Infusion (CSII) via insulin infusion pumps of varying manufacturers.

Primary Outcomes

Measure
Comparison of the 4 month A1C change from baseline
time frame: 4 Months

Secondary Outcomes

Measure
Compare relative effects of pretreatment with Hylenex recombinant formulations versus standard CSII on hypoglycemia rates
time frame: 12 Months
Compare relative effects of pretreatment with Hylenex recombinant formulations versus standard CSII on mean glucose and glucose variability
time frame: 12 Months
Compare relative effects of pretreatment with Hylenex recombinant formulations versus standard CSII on local tolerability assessments
time frame: 12 Months
Compare relative effects of pretreatment with Hylenex recombinant formulations versus standard CSII on immunogenicity
time frame: 12 Months
Compare relative effects of pretreatment with Hylenex recombinant formulations versus standard CSII on Adverse Event rates
time frame: 12 Months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Male or female of age 18 or older with a history of T1DM for at least 12 months. 2. A1C 6.5 - 9.5% (inclusive) based on central laboratory results. 3. Fasting C-peptide < 0.6 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 U/day. 6. Subjects who routinely use CGM (defined as average CGM use 5 or more days per week over the preceding 3 months) and those who do not routinely use 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. Subjects 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 subject'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 BP consistently >100 mm Hg) are exclusionary 5. As judged by the Investigator, clinically significant active disease of the gastrointestinal, cardiovascular (including history of stroke, a history of arrhythmia or conduction delays on ECG), hepatic, neurological, renal, genitourinary, pulmonary, or hematological systems of such severity as to impede the subject'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 subject. 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 (see Section 8.3), insulin action, glucose utilization, or recovery from hypoglycemia (including systemic pharmacologic corticosteroid). Use of pramlintide or a GLP1 receptor agonist is NOT exclusionary but subjects using these agents will be subjected to stratified randomization. Use of aspirin (ASA) up to 325 mg/day is NOT exclusionary but should be noted for analysis. 9. Hypoglycemic unawareness of such severity as to impede the subject'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.

Additional Information

Official title CONtinuous Subcutaneous Insulin Infusion STudy ENrolling Type 1 (CONSISTENT 1) 1: Evaluation of Metabolic Outcomes and Safety of Hylenex Recombinant (Hyaluronidase Human Injection) Used as a Preadministration Infusion Site Treatment in Subjects With Type 1 Diabetes (T1DM) Using Continuous Subcutaneous Insulin Infusion (CSII)
Description When a healthy individual begins a meal, there is a rapid insulin response. Currently available subcutaneously injected or infused human insulin products (both recombinant human insulin and rapid acting insulin analogs) do not replicate the natural insulin response to a meal challenge. Instead, subcutaneously injected or infused insulins enter the bloodstream relatively slowly, and, likewise, they tend to have a duration of action that is too long to optimally mimic normal physiology. As a consequence, patients with diabetes have inadequate levels of insulin present at the initiation of a meal and very often have too much systemic insulin between meals. This may lead to hyperglycemia in the early post-meal time period, followed by risk of hypoglycemia between meals. Building on Halozyme's experience with rHuPH20 (active component of Hylenex recombinant) co-injected with insulin products studied in both the clinical setting and in the take-home setting along with experience using rHuPH20 with CSII, this Phase 4 study is designed to demonstrate non-inferiority 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 A1C in patients with Type 1 diabetes mellitus
Trial information was received from ClinicalTrials.gov and was last updated in August 2013.
Information provided to ClinicalTrials.gov by Halozyme Therapeutics.