Trial Outcomes & Findings for A Study of Continuous Subcutaneous Insulin Infusion (CSII) Pump Function in Subjects With Type 1 Diabetes With Recombinant Human Hyaluronidase (rHuPH20) (NCT NCT03662334)

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

14 participants

Primary outcome timeframe

0-6 hours

Results posted on

2019-02-01

Participant Flow

All three parts (Parts 1, 2, and 3) of this exploratory study were to use a cross-over design that would maximize efficiency while minimizing sample size. Only Part 2 of this study was conducted; thus, all 14 participants were enrolled in Part 2 only.

Participant milestones

Participant milestones
Measure	Hyaluronidase Human Injection/Sham Injection Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Sham Injection/Hyaluronidase Human Injection Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Part 1: Treatment Period 1 STARTED	0	0
Part 1: Treatment Period 1 COMPLETED	0	0
Part 1: Treatment Period 1 NOT COMPLETED	0	0
Part 1: Treatment Period 2 STARTED	0	0
Part 1: Treatment Period 2 COMPLETED	0	0
Part 1: Treatment Period 2 NOT COMPLETED	0	0
Part 2: Treatment Period 1 (2 Days) STARTED	7	7
Part 2: Treatment Period 1 (2 Days) COMPLETED	7	7
Part 2: Treatment Period 1 (2 Days) NOT COMPLETED	0	0
Part 2: Treatment Period 2 (2 Days) STARTED	7	7
Part 2: Treatment Period 2 (2 Days) COMPLETED	6	7
Part 2: Treatment Period 2 (2 Days) NOT COMPLETED	1	0
Part 3: Treatment Period 1 STARTED	0	0
Part 3: Treatment Period 1 COMPLETED	0	0
Part 3: Treatment Period 1 NOT COMPLETED	0	0
Part 3: Treatment Period 2 STARTED	0	0
Part 3: Treatment Period 2 COMPLETED	0	0
Part 3: Treatment Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Hyaluronidase Human Injection/Sham Injection Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Sham Injection/Hyaluronidase Human Injection Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Part 2: Treatment Period 2 (2 Days) Intended Changes to Clamp Procedure	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Hyaluronidase Human Injection/Sham Injection n=7 Participants Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Sham Injection/Hyaluronidase Human Injection n=7 Participants Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.	Total n=14 Participants Total of all reporting groups
Age, Continuous	43.6 years STANDARD_DEVIATION 8.90 • n=113 Participants	40.4 years STANDARD_DEVIATION 14.84 • n=163 Participants	42.0 years STANDARD_DEVIATION 11.87 • n=160 Participants
Sex: Female, Male Female	2 Participants n=113 Participants	2 Participants n=163 Participants	4 Participants n=160 Participants
Sex: Female, Male Male	5 Participants n=113 Participants	5 Participants n=163 Participants	10 Participants n=160 Participants
Race/Ethnicity, Customized White or Caucasian	7 Participants n=113 Participants	7 Participants n=163 Participants	14 Participants n=160 Participants

PRIMARY outcome

Timeframe: 0-6 hours

Population: The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 0-10 hours

Population: Safety Population: all randomized participants exposed to at least one dose of study drug

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.

Outcome measures

Outcome measures
Measure	Hyaluronidase Human Injection/Sham Injection n=7 Participants Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Sham Injection/Hyaluronidase Human Injection n=7 Participants Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Part 2: Time to Reduction in Plasma Glucose by 80 Milligrams Per Deciliter (mg/dL) Following CSII Bolus First Intervention	5.58 hours	5.23 hours
Part 2: Time to Reduction in Plasma Glucose by 80 Milligrams Per Deciliter (mg/dL) Following CSII Bolus Second Intervention	4.63 hours	5.32 hours

PRIMARY outcome

Timeframe: 0-12 hours

Population: The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to approximately 10 hours

Population: The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to approximately 22 hours

Population: The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to approximately 22 hours

Population: The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to approximately 22 hours

Population: The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to approximately 22 hours

Population: The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 0 to 1 hour

Population: The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 to approximately 22 hours

Population: The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to approximately 22 hours

Population: The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to approximately 22 hours

Population: The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to approximately 10 hours

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Hyaluronidase Human Injection/Sham Injection n=7 Participants Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Sham Injection/Hyaluronidase Human Injection n=7 Participants Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Part 2: Plasma Glucose Concentration Over Time First Intervention	299 mg/dL	341 mg/dL
Part 2: Plasma Glucose Concentration Over Time Second Intervention	350 mg/dL	445 mg/dL

SECONDARY outcome

Timeframe: up to approximately 10 hours

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Hyaluronidase Human Injection/Sham Injection n=7 Participants Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Sham Injection/Hyaluronidase Human Injection n=7 Participants Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Part 2: Insulin Analog Serum Concentration as a Function of Time Following Bolus Insulin Infusion First Intervention	1341.8 picomolar	805.1 picomolar
Part 2: Insulin Analog Serum Concentration as a Function of Time Following Bolus Insulin Infusion Second Intervention	688.5 picomolar	1092.6 picomolar

SECONDARY outcome

Timeframe: up to approximately 12 hours

Population: The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to approximately 12 hours

Population: The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Outcome measures

Outcome data not reported

Adverse Events

Hyaluronidase Human Injection

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Sham Injection

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Hyaluronidase Human Injection n=14 participants at risk Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of either Treatment Period 1 or Treatment Period 2. The two periods were separated by a 3- to 7-day washout period.	Sham Injection n=14 participants at risk Participants received pretreatment of 1 mL sham injection on Day 1 of either Treatment Period 1 or Treatment Period 2. The two periods were separated by a 3- to 7-day washout period.
General disorders Injection Site Pain	14.3% 2/14 • 155 days	0.00% 0/14 • 155 days
General disorders Injection Site Haematoma	7.1% 1/14 • 155 days	0.00% 0/14 • 155 days
General disorders Pyrexia	0.00% 0/14 • 155 days	7.1% 1/14 • 155 days
Gastrointestinal disorders Abdominal Pain Upper	7.1% 1/14 • 155 days	0.00% 0/14 • 155 days
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/14 • 155 days	7.1% 1/14 • 155 days
Metabolism and nutrition disorders Hyperglycaemia	7.1% 1/14 • 155 days	0.00% 0/14 • 155 days

Additional Information

Dimitrios Chondros, M.D., Chief Medical Officer

Halozyme Therapeutics

Phone: 858-794-8889

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee All information obtained as a result of this study or during the conduct of this study will be regarded as confidential. The Investigator agrees to use the information for the purpose of carrying out this study and for no other purpose, unless written permission from the sponsor (Halozyme) is obtained.
Publication restrictions are in place

Restriction type: OTHER