A Study of Continuous Subcutaneous Insulin Infusion (CSII) Pump Function in Subjects With Type 1 Diabetes With Recombinant Human Hyaluronidase (rHuPH20) (HALO-117-406)

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)

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).

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: Rapid Acting insulin with pre-treatment of rHuPH20; Device: 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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • Profil Institute for Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Hylenex recombinant; Comparing the preadministration of Hylenex recombinant in the setting of continuous subcutaneous insulin infusion (CSII).	Drug: Rapid Acting insulin with pre-treatment of rHuPH20; Hylenex recombinant will be administered via infusion sets and insulin pumps. These will be compatible with component tubing system attached to the insulin infusion site and will be placed in the lower abdominal area.; Other Names: Humalog; Hylenex
SHAM_COMPARATOR: Sham Injection; Comparing the preadministration of a sham injection in the setting of CSII.	Device: Sham injection; A sham injection will be administered via infusion sets and insulin pumps. These will be compatible with component tubing system attached to the insulin infusion site and will be placed in the lower abdominal area.; Other Names: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Area Under the Curve (AUC) of Glucose Infusion Rate (GIR) From 0-6 Hours		0-6 hours
Part 2: Time to Reduction in Plasma Glucose by 80 Milligrams Per Deciliter (mg/dL) Following CSII Bolus	Time to reduction is reported as the maximum time it took for any participant receiving each treatment sequence to achieve a reduction in plasma glucose by 80 mg/dL. During the course of the study, it became difficult to establish a stable hyperglycemic plateau with a target glucose level of 220 mg/dL, even after adjusting several operational parameters. The study was stopped early, prior to enrolling the planned 24 participants for Part 2. Thus, analysis for this endpoint was not conducted. Raw data (as a maximum) are reported.	0-10 hours
Part 3: Time to Achieve Plasma Glucose >90 mg/dL After Release of Hypoglycemic CSII Clamp		0-12 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Time-action Profile, Assessed by GIR in Euglycemic Participants		up to approximately 10 hours
Part 1: Mean Maximum Concentration (Cmax)		up to approximately 22 hours
Part 1: Time to Achieve Maximum Concentration (Tmax)		up to approximately 22 hours
Part 1: Early Time to 50% Maximum Serum Insulin Concentration (t50%) Max		up to approximately 22 hours
Part 1: Time to 50% of Total AUC (AUC0-last)		up to approximately 22 hours
Part 1: Fractional and Absolute AUC0-1hr		0 to 1 hour
Part 1: Fractional and Absolute AUC2hr-end		2 to approximately 22 hours
Part 1: Area Under the Curve From Time Zero to the Last Measureable Concentration (AUC0-last)		up to approximately 22 hours
Part 1: Mean Residence Time (MRT)		up to approximately 22 hours
Part 2: Plasma Glucose Concentration Over Time	Plasma glucose concentration over time is reported as the maximum concentration for any participant receiving each treatment sequence. During the course of the study, it became difficult to establish a stable hyperglycemic plateau with a target glucose level of 220 mg/dL, even after adjusting several operational parameters. The study was stopped early, prior to enrolling the planned 24 participants for Part 2. Thus, analysis for this endpoint was not conducted. Raw data (as a maximum) are reported.	up to approximately 10 hours
Part 2: Insulin Analog Serum Concentration as a Function of Time Following Bolus Insulin Infusion	Insulin analog serum concentration is reported as the maximum concentration for any participant receiving each treatment sequence. During the course of the study, it became difficult to establish a stable hyperglycemic plateau with a target glucose level of 220 mg/dL, even after adjusting several operational parameters. The study was stopped early, prior to enrolling the planned 24 participants for Part 2. Thus, analysis for this endpoint was not conducted. Raw data (as a maximum) are reported.	up to approximately 10 hours
Part 3: Plasma Glucose Concentration Over Time		up to approximately 12 hours
Part 3: Insulin Analog Serum Concentration as a Function of Time Following Termination of Insulin Infusion		up to approximately 12 hours

Collaborators and Investigators

• Sponsor: Halozyme Therapeutics

Publications and helpful links

Helpful Links

• Halozyme Therapeutics

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 3, 2013
• Primary Completion (ACTUAL): February 27, 2014
• Study Completion (ACTUAL): February 27, 2014

Study Registration Dates

• First Submitted: August 13, 2018
• First Submitted That Met QC Criteria: September 5, 2018
• First Posted (ACTUAL): September 7, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 1, 2019
• Last Update Submitted That Met QC Criteria: January 30, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Diabetes; Insulin; Type 1 Diabetes Mellitus; Type 1 Diabetes; CSII; Insulin pump; T1DM; Hylenex; rHuPH20; Continuous Subcutaneous Insulin Infusion (CSII); recombinant human hyaluronidase (rHuPH20); Recombinant hyaluronidase
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin, Short-Acting
• Other Study ID Numbers: HALO-117-406