Trial Outcomes & Findings for Hyaluronidase Effect on Infusion Set Life (NCT NCT02199028)

NCT ID: NCT02199028

Last Updated: 2019-10-11

Results Overview

Average (mean) days of wear are presented for each group. A longer period of wear was considered a better outcome.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 30 participants
• Primary outcome timeframe: Up to 4 weeks
• Results posted on: 2019-10-11

Participant Flow

A total of 30 subjects with Type 1 diabetes between 12-45 years were enrolled at 2 academic medical centers. 28 subjects completed the full 4 weeks of the study. 2 subjects discontinued for the study early. The last subject completed in March 2015.

Participant milestones

Measure	Hylenex, Then Control Participants assigned to active treatment arm (Hylenex) for weeks 1 and 3. On weeks 1 and 3 (Hylenex weeks) subjects injected 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear. On weeks 2 and 4 (control weeks) no Hylenex was administered.	Control, Then Hylenex Participants were first assigned to the control arm. They received active treatment (Hylenex) on weeks 2 and 4. On weeks 1 and 3 (control weeks) no Hylenex was administered. On weeks 2 and 4 (Hylenex weeks) subjects injected 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear.
Week 1 STARTED	15	15
Week 1 COMPLETED	14	15
Week 1 NOT COMPLETED	1	0
Week 2 STARTED	14	15
Week 2 COMPLETED	14	15
Week 2 NOT COMPLETED	0	0
Week 3 STARTED	14	15
Week 3 COMPLETED	13	15
Week 3 NOT COMPLETED	1	0
Week 4 STARTED	13	15
Week 4 COMPLETED	13	15
Week 4 NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Hylenex, Then Control Participants assigned to active treatment arm (Hylenex) for weeks 1 and 3. On weeks 1 and 3 (Hylenex weeks) subjects injected 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear. On weeks 2 and 4 (control weeks) no Hylenex was administered.	Control, Then Hylenex Participants were first assigned to the control arm. They received active treatment (Hylenex) on weeks 2 and 4. On weeks 1 and 3 (control weeks) no Hylenex was administered. On weeks 2 and 4 (Hylenex weeks) subjects injected 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear.
Week 1 Adverse Event	1	0
Week 3 Adverse Event	1	0

Baseline Characteristics

Hyaluronidase Effect on Infusion Set Life

Baseline characteristics by cohort

Measure	Hylenex, Then Control n=15 Participants Participants were first assigned to the control arm. They received active treatment (Hylenex) on weeks 2 and 4. On weeks 1 and 3 (control weeks) no Hylenex was administered. On weeks 2 and 4 (Hylenex weeks) subjects injected 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear.	Control, Then Hylenex n=15 Participants Participants were first assigned to the control arm. They received active treatment (Hylenex) on weeks 2 and 4. On weeks 1 and 3 (control weeks) no Hylenex was administered. On weeks 2 and 4 (Hylenex weeks) subjects injected 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear.	Total n=30 Participants Total of all reporting groups
Age, Categorical <=18 years	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	24.80552 years STANDARD_DEVIATION 8.22924 • n=5 Participants	30.06919 years STANDARD_DEVIATION 8.33594 • n=7 Participants	27.52718 years STANDARD_DEVIATION 8.57883 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants	15 participants n=7 Participants	30 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 4 weeks

Population: Thirty subjects were enrolled in this study; 28 completed all scheduled visits. Therefore, 117 total weeks of infusion set wear were available for analysis including 58 hyaluronidase weeks and 59 standard weeks.

Average (mean) days of wear are presented for each group. A longer period of wear was considered a better outcome.

Outcome measures

Measure	Hyaluronidase n=58 week of infusion set wear Infuse 1mL Hyaluronidase at time of infusion set placement and again on Day 3 Hyaluronidase: If assigned to hyaluronidase week, subjects will inject 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set. They will then give a catheter fixed prime of 0.7 cc to clear the infusion set of hyaluronidase. On the morning of day 3 during a Hyaluronidase week, a second dose of 1ml Hylenex (150 units/1ml) will be injected through the catheter hub prior to breakfast using the Duo Infusion Set Tubing. They will then reconnect their pump catheter and give a fixed prime of 0.7 cc to clear the infusion set of hyaluronidase.	Control n=59 week of infusion set wear Subjects will not receive Hyaluronidase during this week
Duration of Insulin Infusion Set Wear as a Measure of the Effect of Hyaluronidase Treatment	5.7 Days of wear Standard Deviation 1.7	5.4 Days of wear Standard Deviation 1.9

SECONDARY outcome

Timeframe: Up to 24 hours post infusion

The effects of hyaluronidase on post-prandial glucodymamic parameters is presented as the estimated glycemic excursion, a composite value which was calculated based on peak glucose concentration (Cmax), time to Cmax (Tmax), time to early half-maximal glucose concentration (t50%), time to late t50%, and area under the curve (AUC) of glucose concentrations at time intervals of 120 and 240 minutes, with or without hyaluronidase. Estimated glycemic excursion for a patient with Type 1 diabetes that is less than 80 mg/dL is considered acceptable.

Outcome measures

Measure	Hyaluronidase n=30 Participants Infuse 1mL Hyaluronidase at time of infusion set placement and again on Day 3 Hyaluronidase: If assigned to hyaluronidase week, subjects will inject 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set. They will then give a catheter fixed prime of 0.7 cc to clear the infusion set of hyaluronidase. On the morning of day 3 during a Hyaluronidase week, a second dose of 1ml Hylenex (150 units/1ml) will be injected through the catheter hub prior to breakfast using the Duo Infusion Set Tubing. They will then reconnect their pump catheter and give a fixed prime of 0.7 cc to clear the infusion set of hyaluronidase.	Control n=30 Participants Subjects will not receive Hyaluronidase during this week
Maximum Glycemic Excursion Day 1 0-1 hour of infusion set	43.5 mg/dL Standard Deviation 44.5	69.5 mg/dL Standard Deviation 47.4
Maximum Glycemic Excursion Day 1 12-24 hours of infusion set	36.9 mg/dL Standard Deviation 35.1	72 mg/dL Standard Deviation 48.8
Maximum Glycemic Excursion Day 2 24-48 hours of infusion set	56.4 mg/dL Standard Deviation 25.9	51.6 mg/dL Standard Deviation 32

SECONDARY outcome

Timeframe: Up to 4 weeks

Population: Only participants in the Hyaluronidase injections group completed diary entries to track pain.

Patients recorded pain experience at the infusion site (at time of injection and pain each day of wear) in subject diaries on a 0-5 pain scale (0 = no pain and 5 = worst pain imaginable).

The number of diary entries are presented by scale category.

Outcome measures

Measure	Hyaluronidase n=107 Diary Entries Infuse 1mL Hyaluronidase at time of infusion set placement and again on Day 3 Hyaluronidase: If assigned to hyaluronidase week, subjects will inject 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set. They will then give a catheter fixed prime of 0.7 cc to clear the infusion set of hyaluronidase. On the morning of day 3 during a Hyaluronidase week, a second dose of 1ml Hylenex (150 units/1ml) will be injected through the catheter hub prior to breakfast using the Duo Infusion Set Tubing. They will then reconnect their pump catheter and give a fixed prime of 0.7 cc to clear the infusion set of hyaluronidase.	Control Subjects will not receive Hyaluronidase during this week
Pain Tolerability of Hyaluronidase Injections "0" on 0-5 pain scale	58 Diary entries	—
Pain Tolerability of Hyaluronidase Injections "1" on 0-5 pain scale	34 Diary entries	—
Pain Tolerability of Hyaluronidase Injections "2" on 0-5 pain scale	11 Diary entries	—
Pain Tolerability of Hyaluronidase Injections "3" on 0-5 pain scale	4 Diary entries	—
Pain Tolerability of Hyaluronidase Injections "4" on 0-5 pain scale	0 Diary entries	—
Pain Tolerability of Hyaluronidase Injections "5" on 0-5 pain scale	0 Diary entries	—

Adverse Events

Hyaluronidase Week

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Control Week

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Hyaluronidase Week n=30 participants at risk Infuse 1mL Hyaluronidase at time of infusion set placement and again on Day 3 Hyaluronidase: If assigned to hyaluronidase week, subjects will inject 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set. They will then give a catheter fixed prime of 0.7 cc to clear the infusion set of hyaluronidase. On the morning of day 3 during a Hyaluronidase week, a second dose of 1ml Hylenex (150 units/1ml) will be injected through the catheter hub prior to breakfast using the Duo Infusion Set Tubing. They will then reconnect their pump catheter and give a fixed prime of 0.7 cc to clear the infusion set of hyaluronidase.	Control Week n=30 participants at risk Subjects will not receive Hyaluronidase during this week
Skin and subcutaneous tissue disorders Erythema >10 mm diameter	53.3% 16/30 • Number of events 20 • Adverse events were recorded during subject's participation in the study (screening to final visit). Adverse events were followed from onset to resolution. Adverse events were recorded during weeks of infusion set wear. In the study a total of 117 weeks of infusion set wear were available for analysis including 58 hyaluronidase weeks and 59 control weeks.	56.7% 17/30 • Number of events 19 • Adverse events were recorded during subject's participation in the study (screening to final visit). Adverse events were followed from onset to resolution. Adverse events were recorded during weeks of infusion set wear. In the study a total of 117 weeks of infusion set wear were available for analysis including 58 hyaluronidase weeks and 59 control weeks.
Skin and subcutaneous tissue disorders Infection at infusion set site	0.00% 0/30 • Adverse events were recorded during subject's participation in the study (screening to final visit). Adverse events were followed from onset to resolution. Adverse events were recorded during weeks of infusion set wear. In the study a total of 117 weeks of infusion set wear were available for analysis including 58 hyaluronidase weeks and 59 control weeks.	3.3% 1/30 • Number of events 1 • Adverse events were recorded during subject's participation in the study (screening to final visit). Adverse events were followed from onset to resolution. Adverse events were recorded during weeks of infusion set wear. In the study a total of 117 weeks of infusion set wear were available for analysis including 58 hyaluronidase weeks and 59 control weeks.
Skin and subcutaneous tissue disorders Infection at sensor site	3.3% 1/30 • Number of events 1 • Adverse events were recorded during subject's participation in the study (screening to final visit). Adverse events were followed from onset to resolution. Adverse events were recorded during weeks of infusion set wear. In the study a total of 117 weeks of infusion set wear were available for analysis including 58 hyaluronidase weeks and 59 control weeks.	3.3% 1/30 • Number of events 1 • Adverse events were recorded during subject's participation in the study (screening to final visit). Adverse events were followed from onset to resolution. Adverse events were recorded during weeks of infusion set wear. In the study a total of 117 weeks of infusion set wear were available for analysis including 58 hyaluronidase weeks and 59 control weeks.
Skin and subcutaneous tissue disorders Rash	3.3% 1/30 • Number of events 1 • Adverse events were recorded during subject's participation in the study (screening to final visit). Adverse events were followed from onset to resolution. Adverse events were recorded during weeks of infusion set wear. In the study a total of 117 weeks of infusion set wear were available for analysis including 58 hyaluronidase weeks and 59 control weeks.	3.3% 1/30 • Number of events 1 • Adverse events were recorded during subject's participation in the study (screening to final visit). Adverse events were followed from onset to resolution. Adverse events were recorded during weeks of infusion set wear. In the study a total of 117 weeks of infusion set wear were available for analysis including 58 hyaluronidase weeks and 59 control weeks.

Additional Information

Dr Bruce Buckingham

Stanford University

Phone: (408) 356-0911

Email: buckingham@stanford.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place