Clinical trial NCT03662334: A Study of Continuous Subcutaneous Insulin Infusion (CSII) Pump Function in Subjects With Type 1 Diabetes With Recombinant Human Hyaluronidase (rHuPH20)
Official title: A Phase 4, Double Blind, Single Center, Randomized, Cross-Over Study of Continuous Subcutaneous Insulin Infusion (CSII) Pump Functionality in Subjects With Type 1 Diabetes Comparing Pretreatment vs. No Pretreatment With Recombinant Human Hyaluronidase (rHuPH20)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 1 Diabetes Mellitus
Keywords: Diabetes
Type 1 Diabetes Mellitus
Type 1 Diabetes
T1DM
Continuous Subcutaneous Insulin Infusion (CSII)
CSII
Insulin pump
Insulin
rHuPH20
Hylenex
recombinant human hyaluronidase (rHuPH20)
Recombinant hyaluronidase
Lead sponsor: Halozyme Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-09-07
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The goal of this study is to determine if Hylenex recombinant leads to changes in the insulin time-action profiles and glucose responses when preadministered in the setting of continuous subcutaneous insulin infusion (CSII) compared to CSII without Hylenex recombinant (sham injection).

Detailed description: There is a recognized need for more rapid insulin action than is available from current rapid-acting analog products. In addition, current products have inconstant absorption and action profiles over the course of infusion set life. Previous human studies of prandial insulin preparations have used co-mixtures of rHuPH20 (study drug) with insulin delivered to study participants by subcutaneous injection and have demonstrated acceleration of insulin absorption and action. CSII has been used clinically for the treatment of diabetes over the last three decades, and a previous study using a co-mixture of rHuPH20 during CSII showed that the combination resulted in a more consistent and ultrafast profile of insulin absorption and action across infusion set use as compared to rapid analog insulin alone.

Eligibility criteria: Inclusion Criteria:

1. Male or female participants between the ages 18 and 65 years, inclusive.
2. Females of child-bearing potential must agree to use a standard and effective means of birth control for the duration of the study. Adequate contraceptive measures include oral or injectable contraceptives, sterilization, intra-uterine device (IUD), barrier methods, or abstinence.
3. Participants with type 1 diabetes mellitus treated with insulin (multiple daily injections or continuous subcutaneous insulin infusion \[CSII\]) diagnosed ≥ 12 months prior to enrollment
4. Body mass index (BMI) 18.0 to 32.0 kilograms per meters squared (kg/m\^2)
5. HbA1c (glycated hemoglobin A1c) ≤ 10% based on local laboratory results
6. Fasting C-peptide \< 0.6 nanograms per milliliter (ng/mL)
7. Current treatment with insulin \<1.2 Units per kg per day (U/kg/day)
8. Participant should be in good general health based on medical history and physical examination, without medical conditions that might prevent the completion of study drug injections and assessments required in this protocol

Exclusion Criteria:

1. Inability to comply with study requirements as judged by the Investigator
2. Known or suspected allergy to any component of any of the study drugs in this trial
3. A participant who has proliferative retinopathy or maculopathy, severe gastroparesis, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator
4. As judged by the Investigator, clinically significant active disease of the gastrointestinal, cardiovascular (including a history of arrhythmia or conduction delays on electrocardiogram), hepatic, neurological, renal, genitourinary, or hematological systems
5. As judged by the Investigator, uncontrolled hypertension (diastolic blood pressure ≥ 100 millimeters of mercury \[mmHg\] and/or systolic blood pressure ≥ 160 mmHg after 5 minutes in the supine position)
6. History of any illness or disease that in the opinion of the Investigator might confound the results of the trial 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. Anemia with hemoglobin less than lower limits of normal at screening is specifically exclusionary
8. Use of drugs that may interfere with the interpretation of trial results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia, or drugs not permitted according to Hylenex recombinant package insert
9. Recurrent major hypoglycemia or hypoglycemic unawareness, as judged by the Investigator
10. Current addiction to alcohol or substances of abuse as determined by the Investigator
11. Blood donation (\> 500 mL) within the previous 8 weeks (56 days) prior to Day -1 of Treatment Period 1
12. Pregnancy, breast-feeding, the intention of becoming pregnant, or not using adequate contraceptive measures (adequate contraceptive measures consist of sterilization, IUD, oral or injectable contraceptives, or barrier methods)
13. Mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation in this study
14. Participation in any other clinical trial and receipt of any investigational drug within 4 weeks of Day -1 of Treatment Period 1
15. Any condition (intrinsic or extrinsic) that in the judgment of the Investigator will interfere with trial participation or evaluation of data
16. Positive for human immunodeficiency virus (HIV), Hepatitis C or Hepatitis B
17. Tobacco and nicotine use within 3 months prior to Day 1 of Treatment Period 1 or use during the study

Primary outcomes:
measure: Part 1: Area Under the Curve (AUC) of Glucose Infusion Rate (GIR) From 0-6 Hours
timeFrame: 0-6 hours
measure: Part 2: Time to Reduction in Plasma Glucose by 80 Milligrams Per Deciliter (mg/dL) Following CSII Bolus
timeFrame: 0-10 hours
measure: Part 3: Time to Achieve Plasma Glucose >90 mg/dL After Release of Hypoglycemic CSII Clamp
timeFrame: 0-12 hours
Secondary outcomes:
measure: Part 1: Time-action Profile, Assessed by GIR in Euglycemic Participants
timeFrame: up to approximately 10 hours
measure: Part 1: Mean Maximum Concentration (Cmax)
timeFrame: up to approximately 22 hours
measure: Part 1: Time to Achieve Maximum Concentration (Tmax)
timeFrame: up to approximately 22 hours
measure: Part 1: Early Time to 50% Maximum Serum Insulin Concentration (t50%) Max
timeFrame: up to approximately 22 hours
measure: Part 1: Time to 50% of Total AUC (AUC0-last)
timeFrame: up to approximately 22 hours
measure: Part 1: Fractional and Absolute AUC0-1hr
timeFrame: 0 to 1 hour
measure: Part 1: Fractional and Absolute AUC2hr-end
timeFrame: 2 to approximately 22 hours
measure: Part 1: Area Under the Curve From Time Zero to the Last Measureable Concentration (AUC0-last)
timeFrame: up to approximately 22 hours
measure: Part 1: Mean Residence Time (MRT)
timeFrame: up to approximately 22 hours
measure: Part 2: Plasma Glucose Concentration Over Time
timeFrame: up to approximately 10 hours
measure: Part 2: Insulin Analog Serum Concentration as a Function of Time Following Bolus Insulin Infusion
timeFrame: up to approximately 10 hours
measure: Part 3: Plasma Glucose Concentration Over Time
timeFrame: up to approximately 12 hours
measure: Part 3: Insulin Analog Serum Concentration as a Function of Time Following Termination of Insulin Infusion
timeFrame: up to approximately 12 hours
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Profil Institute for Clinical Research
state: California
Study officials:
References: