Absorption and Safety With Sustained Use of RELiZORB Evaluation (ASSURE) Study

Absorption and Safety With Sustained Use of RELiZORB Evaluation (ASSURE) Study in Patients With Cystic Fibrosis Receiving Enteral Feeding

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02750501

Acronym

ASSURE

Enrollment

Registered

2016-04-25

Start date

2016-07-20

Completion date

2017-03-30

Last updated

2018-08-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cystic Fibrosis

Keywords

CF, EPI, diabetes, PERT, LCPUFA, DHA, EPA, Omega-3 index

Brief summary

Protocol 0000498: Multicenter, open label study to evaluate the effect of sustained RELiZORB (immobilized lipase) cartridge use during enteral feeding on fat absorption, as well as safety and tolerability of sustained RELiZORB use, in patients with cystic fibrosis and exocrine pancreatic insufficiency.

Detailed description

Study Entry (Day -14): Baseline blood samples collected for plasma and erythrocyte concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic (EPA). Baseline characteristics collected included BMI and cystic fibrosis related diabetes. Observation Period (Day -14 to Day -8): Subjects followed their usual enteral nutrition regimen with pancreatic enzyme replacement therapy (PERT). Run-in Period (Day -7 to Day -1): Subjects used Peptamen 1.5 enteral formula at their normal volume of administration from 500 mL to 1,000 mL per feeding with usual PERT regimen. Treatment Period (Day 0 to Day 90): Subjects used Impact Peptide 1.5 up to a maximum volume of 1,000 mL per feeding with RELiZORB for the 90 day treatment period. Blood screening measurements were repeated at start of treatment period (Day 0), Day 30, Day 60 and Day 90. PERT use with enteral feedings was prohibited. Safety and tolerability were assessed with GI symptom diaries and systematic assessments of adverse events and unanticipated adverse device effects.

Interventions

DEVICERELiZORB (immobilized lipase) cartridge

Hydrolyzing fats from enteral formula, ex vivo, with in-line enteral feed RELiZORB (immobilized lipase) cartridge

OTHERImpact Peptide 1.5

Impact Peptide 1.5 at a volume of administration from 500 mL to 1,000 mL per enteral feeding

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

4 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Confirmed diagnosis of cystic fibrosis 2. Documented history of exocrine pancreatic insufficiency 3. Enteral formula use a minimum of 4x/week, using PERT, consuming an unrestricted fat diet, and willing to use Peptamen 1.5 and Impact Peptide 1.5 4. Written informed consent or assent.

Exclusion criteria

1. Uncontrolled diabetes mellitus 2. Signs and symptoms of liver cirrhosis or portal hypertension 3. Lung or liver transplant 4. Active cancer currently receiving cancer treatment 5. Crohn's or celiac disease, infectious gastroenteritis, sprue, lactose intolerance, inflammatory bowel disease

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline of Erythrocyte Omega-3 Index % (DHA+EPA)	Day 0 to Day 90	Change from baseline Day 0 to Day 90 of erythrocyte tissue composition % of the omega-3 index

Secondary

Measure	Time frame	Description
Unanticipated Adverse Device Effects (UADE)	RELiZORB Treatment Period (Day 0-Day 90): 90 days with additional 30 days of follow up.	A UADE is analogous to a serious adverse event (SAE), defined as an AE, occurring at any exposure to the therapeutic agent, that results in any of the following outcomes: death, life-threatening AE, inpatient hospitalization or prolonged existing hospitalization, a persistent or significant disability or incapacity or a congenital anomaly/birth defect.
Changes in Plasma Concentration Total DHA+EPA	RELiZORB Treatment Period (Day 0-Day 90): 90 days	Changes in plasma concentration total DHA+EPA from baseline (Day 0 to Day 90).
Erythrocyte Composition (%) of DHA	RELiZORB Treatment Period (Day 0-Day 90): 90 days	Changes over time in erythrocyte composition (%) for total DHA in ITT population (n=39)
Erythrocyte Composition (%) Ratio of n6/n3 Fatty Acids	RELiZORB Treatment Period (Day 0-Day 90): 90 days	Change from baseline to Day 90 in n6/n3 ratio in erythrocytes
Plasma Composition (%) Ratio of n6/n3 Fatty Acids.	RELiZORB Treatment Period (Day 0-Day 90): 90 days	Change over time in n6/n3 ratio in plasma in the ITT population
Erythrocyte Composition (%) of EPA	RELiZORB Treatment Period (Day 0-Day 90): 90 days	Changes over time in erythrocyte composition (%) for EPA in ITT population

Other

Measure	Time frame	Description
GI Symptoms	Observation, Baseline and RELiZORB Treatment periods (Day -14 to Day 90): 104 days with additional 30 days of follow up.	GI symptoms recorded in GI diaries by subject and/or caregiver.

Countries

United States

Participant flow

Recruitment details

Recruitment was conducted through Cystic Fibrosis Care Centers.

Pre-assignment details

7-day Observation Period: Maintain usual enteral feeding (EF) regimen. 7-day Run-in period: Maintain usual EF volume up to a max of 1000 mL using standard formula for at least 5 days. 49 subjects signed consent; 5 screen failed; 44 started the observation period; 39 completed observation and run-in periods entering the treatment period.

Participants by arm

Arm	Count
Single Arm: Open Label RELiZORB cartridge and Impact Peptide 1.5 with enteral feeding 500 mL to 1,000 mL per enteral feeding for a period of 90 days. RELiZORB: Novel enteral feeding in-line digestive enzyme cartridge Impact Peptide 1.5: Impact Peptide 1.5 at a volume of administration from 500 mL to 1,000 mL per enteral feeding	39
Total	39

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	4
Overall Study	G-tube came out	1
Overall Study	Non-compliant use of PERT	1
Overall Study	Physician Decision	1
Overall Study	Protocol Violation	1

Baseline characteristics

Characteristic	Single Arm: Open Label
Age, Categorical <=18 years	34 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	5 Participants
BMI	17.7 weight (kg) / [height (m)]2 STANDARD_DEVIATION 1.8
Cystic fibrosis related diabetes Cystic fibrosis related diabetes	9 Participants
Cystic fibrosis related diabetes Non-cystic fibrosis related diabetes	30 Participants
Erythrocyte omega-3 index %	4.43 % of omega-3 index of RBC membrane STANDARD_DEVIATION 2.05
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	2 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	37 Participants
Sex: Female, Male Female	15 Participants
Sex: Female, Male Male	24 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 44	0 / 39
other Total, other adverse events	4 / 44	23 / 39
serious Total, serious adverse events	2 / 44	0 / 39

Outcome results

Primary

Change From Baseline of Erythrocyte Omega-3 Index % (DHA+EPA)

Change from baseline Day 0 to Day 90 of erythrocyte tissue composition % of the omega-3 index

Time frame: Day 0 to Day 90

Population: Intent to treat population = 39 subjects who received at least one exposure to RELiZORB. Analysis group is 38 due to one subject discontinuing prior to Visit 3.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
RELiZORB Cartridge With Standard Enteral Formula	Change From Baseline of Erythrocyte Omega-3 Index % (DHA+EPA)	5.01 percentage of omega-3 composition	Standard Error 0.4

Secondary