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Trial registered on ANZCTR


Registration number
ACTRN12620000021976
Ethics application status
Approved
Date submitted
18/09/2019
Date registered
14/01/2020
Date last updated
14/01/2020
Date data sharing statement initially provided
14/01/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Feasibility of an Investigational Extended Wear Infusion Set for Continuous Subcutaneous Insulin Infusion (CSII) in Patients with Type 1 Diabetes Mellitus (T1DM).
Scientific title
Feasibility of an Investigational Extended Wear Infusion Set for Continuous Subcutaneous Insulin Infusion (CSII) in Type 1 Diabetes Mellitus (T1DM) Participants.
Secondary ID [1] 299315 0
Capillary Biomedical, Inc., protocol 150-1072-00 Rev. X1
Universal Trial Number (UTN)
Trial acronym
"FEXIS”: (Feasibility of an Extended Wear CSII Set in Participants with
T1DM)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 Diabetes Mellitus 314453 0
Condition category
Condition code
Metabolic and Endocrine 312788 312788 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a prospective, non-randomized, home-use feasibility study of device performance,
usability, tolerability, and safety of the Capillary Biomedical, Inc. (CapBio) Achilles infusion set for continuous subcutaneous insulin infusion (CSII or insulin pump therapy) in up to 20 participants diagnosed with type 1 diabetes mellitus (T1DM).

The CapBio Achilles infusion set is a sterile single use device designed to be used with commercially available infusion pumps (e.g., Medtronic MiniMed). The investigational Achilles infusion set contains a coil reinforced soft polymer indwelling cannula with one distal and three proximal holes.

The primary objective of this study is to determine feasibility and device performance of the
CapBio Achilles infusion set over 2 extended home use wear periods of up to 7 days each during routine therapeutic insulin infusion. Feasibility is evidenced by the absence of uncontrolled hyperglycemia and/or suspected infusion set cannula occlusion.
Secondary objectives include the assessment of standard glucose control measures obtained from CGM, including observed hyper- and hypoglycemic episodes, patient tolerability (patient comfort) during wear period, cannula dislodgment, inability to pierce skin or leakage, and adverse events (infusion site reaction/infection, etc.). Regarding Week 1, patient comfort, cannula dislodgment, inability to pierce skin or leakage, and adverse events such as infusion site reactions/infections, etc. are secondary outcomes of this study.

All staff on the study will be trained on the study and associated procedures prior to undertaking any study related activities. A principal investigator with adequate medical training will oversee the study procedures associated with the trial. A dedicated study coordinator will assist with the day to day activities of the study. The existing patient population at the study center will be screened for study eligibility within 21 days of planned study enrollment Eligible participants will complete written informed consent and be assigned a study identifier.

The study is comprised of 3 periods. Each period is initiated at the study center and followed by a home-use phase of up to 7 days:
During home-use periods, participants will conduct daily visual infusion site inspection and record pain levels and skin reactions. They will use Dexcom G5 Continuous Glucose Monitor (CGM) (if patient is not routinely using this CGM) to monitor blood glucose and detect hypo and or hyperglycemic episodes or events. If participant experiences an Achilles infusion set device issue, participants shall insert a commercial CSII set to maintain routine insulin therapy. Participants will be provided with training and written instructions if an Achilles device issue occurs at any time during home wear periods. They are instructed to contact study staff as early as possible after infusion set failure and return to the study site at their earliest convenience.
1. Week 1 (t equals 7 days): Trial run with saline infusion. Patients will continue to use their own pump and insulin infusion set while wearing the CapBio Achilles infusion set connected
to a second pump. The reservoir in this pump will be filled with saline and patients will
mimic their insulin basal/bolus pattern on the dummy pump.

2. Week 2 (t equal to or less than 7 days): After successful completion of Week 1, patients will manage their blood glucose (BG) solely with their insulin pump and the Achilles infusion set. BG will be closely monitored with a continuous glucose monitoring (CGM) device. Week 2 is considered complete when either, (1) an Achilles infusion set failure (see below) occurs
and participant needs to insert a commercial CSII set to maintain routine therapy until
they return to the study center, or (2) participant has worn Achilles for the total 7-day
wear period.

3. Week 3 (t equal to or less than 7 days): (Note: Initiation of Week 3 will only occur if Week 2 was completed without any major safety issues, adverse events or other concerns.) After completion of Week 2 patients will return to study center to receive a fresh Achilles infusion set and continue BG management with at home until infusion set failure (see below). BG will be closely monitored with a continuous glucose monitoring (CGM) device. Week 3 is considered complete when either, (1) an Achilles infusion set failure occurs and participant needs to insert a commercial CSII set to maintain routine therapy until they return to the study center, or (2) participant has worn Achilles for the total 7-day wear period.
Infusion set failure is defined as:
1. The occurrence of unexplained hyperglycemia (glucose greater than 250 mg per dL or greater than 14 mmol per L) occurring more than 2 hours after a meal and not responsive to a pump bolus dose where response to the bolus is defined as a fall of at least 50 mg per dL (3 mmol per L) in blood glucose within one hour
2. The occurrence of any hyperglycemic episode (glucose greater than 250 mg per dL or greater than 14 mmol per L) not associated with acute intercurrent illness, but with a concurrent ketone level equal to or greater than 0.6 mmol per L.
3. Signs of infection (e.g. erythema or induration greater than 1 cm in maximal diameter),
4. Occurrence of non-resolvable insulin pump occlusion alarm signal.


Intervention code [1] 315585 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 321614 0
The composite primary objective of this study is to evaluate feasibility and device performance of the Achilles infusion set over three extended home use wear periods of up to 7 days each during routine therapeutic insulin infusion.

The composite primary objective of this study will be assessed through Continuous Glucose Monitor (CGM) readings in coordination with pump data. CGM readings will indicate how well the device performs in terms of insulin absorption, indicated by pump boluses. Therefore, a comparison of time of pump bolus and the CGM readings over the course of two to three hours will be made to asses if the device was successful in delivering insulin to the body to absorb.
Timepoint [1] 321614 0
Week 1, Week 2 and week 3
Secondary outcome [1] 374906 0
Evaluation of, Standard glucose control measures obtained from Continuous Glucose Monitoring (CGM), including observed hyper- and hypoglycemic episodes.
This outcome will be assessed by means of CGM readings and participant diary.
Timepoint [1] 374906 0
Week 2 and week 3
Secondary outcome [2] 374907 0
Evaluation of, Subject tolerability (subject comfort) during wear period.
This outcome will be assessed by means of a Participant diary, which includes a Visual Pain Scale (VAS), to be filled daily with the participant’s feedback and pain level of wearing the device.
Timepoint [2] 374907 0
Week 1, Week 2 and week 3
Secondary outcome [3] 375608 0
Evaluation of, adverse events (infusion site reaction/infection, etc.).
This secondary outcome will be assessed as follows -Participant instructions provide description of adverse events, if identified by the participant, a visit must be made to the clinical site. Therefore, data will be collected by the clinical site, the pump data points (if occlusion occurs), and the CGM readings (in the case of hypo- or hyperglycaemia).
Timepoint [3] 375608 0
Week 1, week 2 and week 3

Eligibility
Key inclusion criteria
1) Participant is 18 – 70 years of age inclusive
2) Participant is in generally good health, as determined by the investigator
3) Participant is willing and able to individually complete written informed consent and
agrees to comply with all study related testing and examinations
4) Participant must be geographically stable (e.g., expects to be available and capable of
returning for all study specified test and examinations) during the study period
5) Participant has been diagnosed with T1DM for at least 12 months
6) C-peptide less than 0.6 nmol per L at screening
7) Subject can provide a minimum of 14 days of insulin pump data to demonstrate pump
use compliance
8) Participant is willing to perform serum ketone measurements whenever the blood
glucose is determined to be greater than 250 mg per dL (14 mmol per L) using a ketone meter
and strips provided by the sponsor
9) Participant has BMI in the range 20 – 35 kg per square metre inclusive
10) Participant has experience infusing a rapid-acting insulin analog for at least 6 months
11) Participant has been using an insulin pump with commercially available infusion sets for
at least 6 months (this includes Automated Insulin Delivery systems)
12) Participant has previous experience using a continuous glucose monitor (CGM) and is
willing to use a CGM for the duration of the study and perform necessary calibration
fingerstick glucose readings
13) Participant has ability to understand and comply with protocol procedures and to
provide informed consent
14) AST and ALT less than or equal to 120 U per L
15) Creatinine less than 1.8 mg per dL
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Participants whose average total daily insulin dose exceeds 85 units per day (i.e. typically
change insulin reservoirs more often than every 3.5 days on average)
2) Participants who routinely change their commercial insulin infusion sets twice weekly or
less often (wear time greater than 3.5 days)
3) Female participant is pregnant or nursing (Documented negative pregnancy test results for female participants required unless participant is menopausal without any spontaneous menstrual cycles for >12 months or key organs have been removed.)
4) Participant has abnormal skin at intended device infusion sites (existing infection, inflammation, burns, or other extensive scarring)
5) Participant has HbA1C greater than 8.5 percent at screening
6) Participant has documented history in last 6 months of severe hypoglycemia associated
with cognitive dysfunction sufficiently severe to require third party intervention or a
history of impaired awareness of hypoglycemia.
7) Participant has a history of diabetic ketoacidosis in the last 6 months
8) Participant has known cardiovascular disease considered to be clinically relevant by the investigator
9) Participant has known arrhythmias considered to be clinically relevant by the investigator
10) Participant has known history of:
a) Cushing’s Disease,
b) pancreatic islet cell tumor, or
c) insulinoma
11) Participant has:
a) Lipodystrophy,
b) extensive lipohypertrophy, as assessed by the investigator
12) Participant is undergoing current treatment with:
a) Systemic oral or intravenous corticosteroids,
b) monoamine oxidase (MAO) inhibitors,
c) non-selective beta-blockers,
d) growth hormone,
e) thyroid hormones, unless use has been stable during the past 3 months
13) Subject has significant history of any of the following, that in the opinion of the
investigator would compromise the subject’s safety or successful study participation:
a) Alcoholism,
b) drug abuse
14) Significant acute or chronic illness, that in the investigator’s opinion, might interfere
with subject safety or integrity of study results
15) Planned operation, MRI or CT which require removal of infusion set or CGM sensor
during wear periods
16) Current participation in another clinical drug or device study
17) AST and ALT greater than 120 U per L
18) Creatinine equal to or greater than 1.8 mg per dL

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
This study is a first-in-human observational study of device feasibility in a known subject
population. As such, there is no definitive relevant statistical hypothesis. A 20 patient sample size was selected based on similar studies of insulin infusion set functionality.

Intended Performance/Success Criteria
Results of this study will be compared to those of Patel et al. Randomized trial of infusion set function: steel versus teflon. Diabetes Technol Ther. 2014 Jan;16(1):15–9., who observed that 30% of infusion sets performed adequately (no premature failure due to mechanical malfunction and no episodes of uncorrectable hyperglycemia prior to the end of 7 days of infusion set wear time), and, among infusion sets that did not exhibit mechanical malfunction, 60% performed adequately by the glucose control metrics for the 7-day wear period. Success criteria willbe considered met if the Achilles infusion set exceeds these performance outcomes.

Populations for Analysis -
Intent-to-Treat (ITT) Analysis Population: All participants who meet all eligibility criteria and
have undergone a first attempt to insert an investigational Achilles infusion set shall be
included in the ITT analysis population.

Safety Analysis Population: All participants who had an investigational cannula inserted.
Per-Protocol (PP) Analysis Population: All patients who completed any part of the 7-day Achilles infusion set evaluation period.

The primary effectiveness analysis will be based on the ITT subject population. Sensitivity
analyses of the primary effectiveness endpoint will be generated based on the PP population.
The ITT population may contain some patients who did not complete the evaluation interval.
This will require the use of imputation methods for missing values. Last observation carry
forward will be used in such case.

The primary safety analysis will be based on the safety population. All secondary and
exploratory effectiveness analyses will use both the ITT and PP populations.

Analysis of the Primary Efficacy Endpoint-
The primary study endpoint is the proportion of Achilles infusion sets that function each day of use, up to 7 days. This endpoint will serve as both the preliminary effectiveness and safety endpoint during the feasibility evaluation.

Analysis of the Secondary Endpoint(s) -
Secondary analyses will use the both ITT and PP populations for analysis.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 14805 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 28054 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 303834 0
Commercial sector/Industry
Name [1] 303834 0
Capillary Biomedical, Inc.
Address [1] 303834 0
8 Faraday, Ste B,
Irvine, CA 92618
Country [1] 303834 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Capillary Biomedical, Inc.
Address
8 Faraday, Ste B,
Irvine, CA 92618
Country
United States of America
Secondary sponsor category [1] 303994 0
None
Name [1] 303994 0
Address [1] 303994 0
Country [1] 303994 0
Other collaborator category [1] 280951 0
Commercial sector/Industry
Name [1] 280951 0
Pacific Clinical Research Group Pty Ltd
Address [1] 280951 0
PO Box 1600,
North Sydney,
NSW 2059
Country [1] 280951 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304349 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 304349 0
St Vincent's Hospital (Melbourne), 41 Victoria Parade, Fitzroy, VIC 3065
Ethics committee country [1] 304349 0
Australia
Date submitted for ethics approval [1] 304349 0
19/09/2019
Approval date [1] 304349 0
10/10/2019
Ethics approval number [1] 304349 0

Summary
Brief summary
Over 1 million patients globally currently manage their Type 1 Diabetes mellitus using continuous subcutaneous insulin infusion with an infusion set that needs to be changed every 3 days. This study will assess the feasibility and device performance of the study device, the Achilles infusion set over three periods during routine insulin infusion.
This study will include 20 participants and has 3 periods:
Period 1 (up to 7 days): Trial run with study device with saline infusion.
Period 2 (up to 7 days): participants will manage their blood glucose solely with their insulin pump and the Achilles infusion set. Blood glucose will be closely monitored with a continuous glucose monitoring (CGM) device.
Period 3 (up to 7 days): Participants will return to study centre to receive a fresh Achilles infusion set and continue blood glucose management at home until infusion set failure or 7 days.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 96638 0
Prof David O'Neal
Address 96638 0
St Vincent's Hospital
Department of Medicine,
Level 4, Building D,
D41 Daly Wing North,
35 Victoria Parade
Fitzroy, Victoria 3065

Country 96638 0
Australia
Phone 96638 0
+61 392882012
Fax 96638 0
+61392882581
Email 96638 0
dno@unimelb.edu.au
Contact person for public queries
Name 96639 0
Miss Druann Greer-Cisneros
Address 96639 0
Capillary Biomedical, Inc.
Administrative Manager,
2 Wrigley, Irvine, CA 92618
Country 96639 0
United States of America
Phone 96639 0
+1 949 317 1700
Fax 96639 0
Email 96639 0
info@capillarybio.com
Contact person for scientific queries
Name 96640 0
Dr Doug Muchmore
Address 96640 0
Capillary Biomedical, Inc.
Medical Director,
2 Wrigley, Irvine, CA 92618
Country 96640 0
United States of America
Phone 96640 0
+1 949 317 1700
Fax 96640 0
Email 96640 0
clinical@capillarybio.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
As per sponsor.
What supporting documents are/will be available?
No other documents available
Summary results
No Results