Safety, Tolerability and Fat Absorption Using Enteral Feeding In-line Enzyme Cartridge (Relizorb)

• Sponsor: Alcresta Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02598128
• Collaborator: (none)
• Enrollment: 34
• Locations: 11
• Arms: 2
• Duration (Months): 7
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Protocol ALCT-0000497 is a multicenter safety, tolerability and fat absorption study that anticipates enrolling 35 male and female subjects (pediatric and adult) with cystic fibrosis. Subjects with confirmed exocrine pancreatic insufficiency will use a novel enteral feeding in-line digestive enzyme cartridge (RELiZORB) connected to enteral pump sets.

Condition or Disease	Intervention/Treatment	Phase
Exocrine Pancreatic Insufficiency	Device: RELiZORB; Device: Placebo	N/A

Detailed Description

Protocol ALCT-0000497 consists of three distinct study periods as follows:

1. In Period A (7 days), subjects will receive Peptamen 1.5 enteral feedings at home.

2. In Period B (11 days), subjects will be randomized to either Group A (active investigational then placebo control) or Group B (placebo control then active investigational) and receive Impact Peptide 1.5 on Days 1 and 9. During the 8-day washout period between Days 1 and 9, subjects will receive Peptamen 1.5.

3. In Period C (9 days), subjects will use RELiZORB during nocturnal enteral feedings with Impact Peptide 1.5.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Study to Evaluate Safety, Tolerability and Fat Absorption Using a Novel Enteral Feeding In-line Digestive Enzyme Cartridge (RELIZORB) in Patients With Cystic Fibrosis Receiving Enteral Feeding
• Study Start Date: Nov 1, 2015
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RELiZORB Treatment (RELiZORB)	Device: RELiZORB; Peptamen 1.5 received Period A and Period B (washout only). Impact Peptide 1.5 received Period B (Days 1 and 9 only) and Period C.; Other Names: Peptamen 1.5 Impact Peptide 1.5
Placebo Comparator: Control Placebo control	Device: Placebo; Sham device

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Adverse Events and Unanticipated Adverse Device Effects [27 days]

   1) Frequency and severity of adverse events; 2) Patients with at least one unanticipated adverse device effects (UADE)

2. Long Chain Polyunsaturated Fatty Acid Plasma Concentration (Intent to Treat Population) [Day 1 first intervention and Day 9 second intervention.]

   AUC analysis of plasma fatty acid concentration for DHA + EPA baseline adjusted over 24-hours

Other Outcome Measures

1. Ease of Use of RELiZORB (Per-Protocol Population) [Period C: Single assessment on Day 19 or 20]

   Effect of enteral nutrition on select activities of daily living. Patients judged the size of breakfast after overnight enteral tube feeding with the following choices: No breakfast; Small breakfast; Normal breakfast; Big breakfast; Other.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Confirmed CF diagnosis with 2 clinical features

2. Documented history of EPI

3. Enteral formula use minimum of 4x/week

4. Written informed consent or assent, as applicable

Exclusion Criteria:

1. Uncontrolled diabetes mellitus

2. Signs and symptoms of liver cirrhosis or portal hypertension

3. Lung/liver transplant

4. Active cancer currently receiving cancer treatment

5. Crohn's or celiac disease, infectious gastroenteritis, sprue, lactose intolerant, inflammatory bowel disease

6. DIOS or fibrosing colonopathy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Los Angeles	Los Angeles	California	United States	90027
2	St. Luke's Cystic Fibrosis Center of Idaho	Boise	Idaho	United States	83712
3	Riley Hospital for Children at Indiana University Health	Indianapolis	Indiana	United States	46202
4	Maine Medical Center	Portland	Maine	United States	04102
5	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
6	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri	United States	63104
7	Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106
8	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
9	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15224
10	Monroe Carell Junior Children's Hospital at Vanderbilt	Nashville	Tennessee	United States	37332
11	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Alcresta Therapeutics, Inc.

Investigators

• Study Director: Russell G. Clayton, Sr., DO, Chief Medical Officer, Alcresta Therapeutics, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alcresta Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02598128
• Other Study ID Numbers: ALCT-0000497
• First Posted: Nov 5, 2015
• Last Update Posted: Jan 25, 2017
• Last Verified: Jan 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Exocrine Pancreatic Insufficiency

Study Results

Participant Flow

Recruitment Details	34 patients enrolled; 33 patients completed the study from 11 U.S. sites.
Pre-assignment Detail	33 eligible patients according to the inclusion/exclusion criteria were randomized in Period B (double-blind crossover) to the study.

Arm/Group Title	Period A: Clinical Treatment Practice (Days -7 to -1)	Crossover Period B: Placebo Then RELiZORB	Crossover Period B: RELiZORB Then Placebo	Period C: Clinical Treatment Practice + RELiZORB (Days 12-20)
Arm/Group Description	Period A was a 7-day baseline period. Patients received Peptamen 1.5 at their normal volume of enteral formula administration up to a maximum of 1000 mL per feeding. Current treatment practice was followed with normal use of oral pancreatic enzyme replacement therapy (PERT) during daily meals and nightly enteral feedings. A gastrointestinal symptom diary was completed for 7 consecutive days. Baseline Day -7 required a clinic visit followed by Days -6 to -1 at home.	Eligible subjects were randomized to Placebo then RELiZORB.	Eligible subjects were randomized to RELiZORB then Placebo.	Period C was the open label clinical treatment period with RELiZORB. All patients used RELiZORB with Impact Peptide 1.5 at their normal volume as in Period A up to a maximum of 1000 mL per feeding. Patients were instructed to use the same daily dose and schedule of oral PERT taken in Period C as in Period A. There were no dietary restrictions. A gastrointestinal symptom diary was completed for 7 consecutive days. Patients received enteral feeding at home from Days 12 to 18 and returned to clinic for their end of study Day 19.
Period Title: Period A: Days -7 to -1
STARTED	34	0	0	0
COMPLETED	33	0	0	0
NOT COMPLETED	1	0	0	0
Period Title: Period A: Days -7 to -1
STARTED	0	17	16	0
COMPLETED	0	17	16	0
NOT COMPLETED	0	0	0	0
Period Title: Period A: Days -7 to -1
STARTED	0	0	0	33
COMPLETED	0	0	0	33
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Clinical Treatment Practice: Period A: Days -7 to -1
Arm/Group Description	Period A was a 7-day baseline period. Patients received Peptamen 1.5 at their normal volume of enteral formula administration up to a maximum of 1000 mL per feeding. Current treatment practice was followed with normal use of oral pancreatic enzyme replacement therapy (PERT) during daily meals and nightly enteral feedings. A gastrointestinal symptom diary was completed for 7 consecutive days. Baseline Day -7 required a clinic visit followed by Days -6 to -1 at home.
Overall Participants	33
Age (Count of Participants)
<=18 years	27 81.8%
Between 18 and 65 years	6 18.2%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	13 39.4%
Male	20 60.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 15.2%
Not Hispanic or Latino	28 84.8%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3%
White	31 93.9%
More than one race	0 0%
Unknown or Not Reported	1 3%
Region of Enrollment (Count of Participants)
United States	33 100%
Baseline Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	41.81 (13.332)
Baseline Height (centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters]	152.32 (19.640)
Baseline Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	17.47 (2.026)

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Adverse Events and Unanticipated Adverse Device Effects
Description	1) Frequency and severity of adverse events; 2) Patients with at least one unanticipated adverse device effects (UADE)
Time Frame	27 days

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Clinical Treatment Practice: Period A: Days -7 to -1	Crossover Period B: Placebo	Crossover Period B: RELiZORB	Clinical Treatment Practice + RELiZORB: Period C: Days 12-20
Arm/Group Description	Period A was a 7-day baseline period. Patients received Peptamen 1.5 at their normal volume of enteral formula administration up to a maximum of 1000 mL per feeding. Current treatment practice was followed with normal use of oral pancreatic enzyme replacement therapy (PERT) during daily meals and nightly enteral feedings. A gastrointestinal symptom diary was completed for 7 consecutive days. Baseline Day -7 required a clinic visit followed by Days -6 to -1 at home.	Non-gastrointestinal adverse events during administration.	Non-gastrointestinal adverse events during administration.	Non-gastrointestinal adverse events during CTP+RELiZORB administration.
Measure Participants	33	33	33	33
Patients With Adverse Events	4 12.1%	6 NaN	1 NaN	2 NaN
Adverse Event by Severity (Mild)	2 6.1%	6 NaN	1 NaN	0 NaN
Adverse Event by Severity (Moderate)	2 6.1%	0 NaN	0 NaN	1 NaN
Adverse Event by Severity (Severe)	0 0%	0 NaN	0 NaN	1 NaN
Patients With At Least One UADE	0 0%	0 NaN	0 NaN	0 NaN

2. Primary Outcome

Title	Long Chain Polyunsaturated Fatty Acid Plasma Concentration (Intent to Treat Population)
Description	AUC analysis of plasma fatty acid concentration for DHA + EPA baseline adjusted over 24-hours
Time Frame	Day 1 first intervention and Day 9 second intervention.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RELiZORB	Control
Arm/Group Description	Subjects receiving RELiZORB at any time in the study.	Subjects receiving placebo at any time in the study.
Measure Participants	33	33
Mean (Standard Deviation) [ug*h/mL]	536.98 (400.519)	192.18 (198.664)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clinical Treatment Practice: Period A: Days -7 to -1, Crossover Period B: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments	The independent variables in the mixed model analysis included fixed effect factors for treatment (placebo or RELiZORB).

3. Other Pre-specified Outcome

Title	Ease of Use of RELiZORB (Per-Protocol Population)
Description	Effect of enteral nutrition on select activities of daily living. Patients judged the size of breakfast after overnight enteral tube feeding with the following choices: No breakfast; Small breakfast; Normal breakfast; Big breakfast; Other.
Time Frame	Period C: Single assessment on Day 19 or 20

Outcome Measure Data

Analysis Population Description

Per Protocol Population.

Arm/Group Title	Clinical Treatment Practice and Relizorb: Period C: Days 12-20
Arm/Group Description	Period C was the open label clinical treatment period with RELiZORB. All patients received RELiZORB with Impact Peptide 1.5 at their normal volume as in Period A up to a maximum of 1000 mL per feeding. Patients were instructed to use the same daily dose and schedule of oral PERT taken in Period C as in Period A. There were no dietary restrictions. A gastrointestinal symptom diary was completed for 7 consecutive days. Patients received enteral feeding at home from Days 12 to 18 and returned to clinic for their end of study Day 19.
Measure Participants	32
No breakfast	11 33.3%
Small breakfast	14 42.4%
Normal breakfast	6 18.2%
Big breakfast	0 0%
Other	1 3%

Adverse Events

Time Frame	20 days
Adverse Event Reporting Description	Safety Population: Non-gastrointestinal Adverse Event by System Organ Class and Preferred Term (n=33)
Arm/Group Title	Clinical Treatment Practice: Period A: Days -7 to -1		Double-Blind Crossover: Period B: Days 1 to 11		Clinical Treatment Practice and Relizorb: Period C: Days 12-20
Arm/Group Description	Period A was a 7-day baseline period. Patients received Peptamen 1.5 at their normal volume of enteral formula administration up to a maximum of 1000 mL per feeding. Current treatment practice was followed with normal use of oral pancreatic enzyme replacement therapy (PERT) during daily meals and nightly enteral feedings. A gastrointestinal symptom diary was completed for 7 consecutive days. Baseline Day -7 required a clinic visit followed by Days -6 to -1 at home.		Period B was the randomized, double-blind, placebo-controlled crossover period. Eligible patients were randomized in a 1:1 ratio to either Placebo-RELiZORB or RELiZORB-Placebo treatment sequences. On two separate administration Days 1 and 9, patients received 500 mL of Impact Peptide1.5 in clinic over a 4h period. Motility and acid suppression medications were discontinued 24h before arrival in clinic. No nocturnal feeding occurred between Days 1-2 and Days 9-10. During the home washout period Days 2 to 8, patients received Peptamen 1.5 for enteral nutrition up to a maximum volume of 1000 mL per feeding. Safety follow up calls were conducted on Days 2 and 10.		Period C was the open label clinical treatment period with RELiZORB. All patients received RELiZORB with Impact Peptide 1.5 at their normal volume as in Period A up to a maximum of 1000 mL per feeding. Patients were instructed to use the same daily dose and schedule of oral PERT taken in Period C as in Period A. There were no dietary restrictions. A gastrointestinal symptom diary was completed for 7 consecutive days. Patients received enteral feeding at home from Days 12 to 18 and returned to clinic for their end of study Day 19.
All Cause Mortality
	Clinical Treatment Practice: Period A: Days -7 to -1		Double-Blind Crossover: Period B: Days 1 to 11		Clinical Treatment Practice and Relizorb: Period C: Days 12-20
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Clinical Treatment Practice: Period A: Days -7 to -1		Double-Blind Crossover: Period B: Days 1 to 11		Clinical Treatment Practice and Relizorb: Period C: Days 12-20
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/33 (3%)		0/33 (0%)		0/33 (0%)
Infections and infestations
Cystic fibrosis pulmonary exacerbation	1/33 (3%)	1	0/33 (0%)	0	0/33 (0%)	0
Other (Not Including Serious) Adverse Events
	Clinical Treatment Practice: Period A: Days -7 to -1		Double-Blind Crossover: Period B: Days 1 to 11		Clinical Treatment Practice and Relizorb: Period C: Days 12-20
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/33 (6.1%)		0/33 (0%)		0/33 (0%)
Nervous system disorders
Headache	2/33 (6.1%)	3	0/33 (0%)	0	0/33 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.