SOLUTION: Study of Oral Liprotamase Unit-Matched Therapy Of Non-Porcine Origin in Patients With Cystic Fibrosis

A Phase 3, Randomized, Open-Label, Assessor-Blind, Noninferiority, Active-Comparator Study Evaluating the Efficacy and Safety of Liprotamase in Subjects With Cystic Fibrosis-Related Exocrine Pancreatic Insufficiency

Liprotamase powder is a non-porcine, soluble and stable mixture of three digestive enzymes including lipase, protease, and amylase. The purpose of the present study is to provide additional efficacy and safety data compared to approved, porcine-derived, enterically-coated and encapsulated pancreatic enzyme replacement therapy. The primary efficacy endpoint of the study will be comparative efficacy measured as the change in the coefficient of fat absorption (CFA) in Cystic Fibrosis patients with exocrine pancreatic insufficiency (EPI).

Liprotamase is stable in stomach and digestive fluids allowing administration in a variety of convenient formulations and with a number of foods without enteric coating.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis; Exocrine Pancreatic Insufficiency
• Intervention / Treatment: Drug: Liprotamase; Drug: porcine (pig) PERT

Detailed Description

Porcine derived enzymes are used for pancreatic enzyme replacement therapy in patients with cystic fibrosis (CF). Liprotamase is a biotechnology-derived enzyme replacement without enteric coating. This is an open-label, assessor blind, parallel group, multicenter, international trial to evaluate the noninferiority of liprotamase and pancrelipase in CF patients aged ≥7 years with pancreatic insufficiency. Subjects were randomized to liprotamase or pancrelipase, dose-matched to pre-study lipase doses. The lower bound of the 95% confidence interval (CI) for noninferiority was -15% for treatment difference in change from baseline coefficient of fat absorption (CFA).

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G IC9
      • Investigator Site 133
• Czechia
  • Brno, Czechia, 62500
    • Investigator Site 501
  • Plzen, Czechia, 305 99
    • Investigator Site 502
• Hungary
  • Csongrad County
    • Szeged, Csongrad County, Hungary, 6720
      • Investigator Site 305
  • Hajdu-Bihar
    • Debrecen, Hajdu-Bihar, Hungary, 4031
      • Investigator Site 303
  • Pest County
    • Torokbalint, Pest County, Hungary, 2045
      • Investigator Site 302
  • Somogy County
    • Mosdos, Somogy County, Hungary, 7257
      • Investigator Site 304
  • Veszprem County
    • Ajka, Veszprem County, Hungary, 8400
      • Investigator site 301
• Israel
  • Jerusalem, Israel, 9124001
    • Investigator Site 601
• Poland
  • Bialystok, Poland, 15-044
    • Investigator site 208
  • Karpacz, Poland, 58-540
    • Investigator site 203
  • Lodz, Poland, 90-329
    • Investigator site 206
  • Lublin, Poland, 20-093
    • Investigator site 201
  • Lublin, Poland, 20-362
    • Investigator site 205
  • Rabka Zdroj, Poland, 34-700
    • Investigator site 202
  • Rzeszow, Poland, 35-312
    • Investigator site 209
  • Sopot, Poland, 81-713
    • Investigator site 204
  • Warszawa, Poland, 01-195
    • Investigator site 207
• Spain
  • Madrid, Spain, 28046
    • Investigator Site 401
  • Madrid, Spain, 28006
    • Investigator Site 403
  • Malaga, Spain, 29009
    • Investigator Site 402
  • Valencia, Spain, 46026
    • Investigator Site 404
• United States
  • California
    • Long Beach, California, United States, 90806
      • Investigator Site 123
    • Los Angeles, California, United States, 90033
      • Investigator site 107
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Investigator site 114
  • Florida
    • Gainesville, Florida, United States, 32610
      • Investigator Site 120
    • Jacksonville, Florida, United States, 32207
      • Investigator Site 102
    • Miami, Florida, United States, 33136
      • Investigator Site 130
    • Orlando, Florida, United States, 32803
      • Investigator Site 117
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Investigator site 110
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Investigator Site 127
    • Glenview, Illinois, United States, 60025
      • Investigator site 109
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Investigator site 104
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Investigator site 105
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • Investigator Site 128
    • Louisville, Kentucky, United States, 40202
      • Investigator Site 122
  • Maine
    • Portland, Maine, United States, 04102
      • Investigator Site 132
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5212
      • Investigator Site 124
    • East Lansing, Michigan, United States, 48823
      • Investigator Site 126
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Investigator Site 134
  • Nevada
    • Las Vegas, Nevada, United States, 89107
      • Investigator Site 135
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Investigator Site 103
    • Toledo, Ohio, United States, 43606
      • Investigator site 113
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Investigator Site 101
    • Oklahoma City, Oklahoma, United States, 73112
      • Investigator Site 136
  • Oregon
    • Portland, Oregon, United States, 97239
      • Investigator Site 119
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Investigator site 106
    • Pittsburgh, Pennsylvania, United States, 15224
      • Investigator site 115
  • Texas
    • Dallas, Texas, United States, 75390
      • Investigator site 111
    • Fort Worth, Texas, United States, 76104
      • Investigator Site 125
    • Houston, Texas, United States, 77030
      • Investigator Site 116
  • Vermont
    • Burlington, Vermont, United States, 05405
      • Investigator Site 121
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Investigator site 112
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Investigator Site 129

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of Cystic Fibrosis based on presentation, genotype and/or sweat chloride
• Fecal elastase <100 mcg/g stool
• Minimum Coefficient of Fat (CFA) at screening while on stable PERT therapy
• Good nutritional status

Exclusion Criteria:

• History or diagnosis of fibrosing colonopathy
• Distal intestinal obstruction syndrome in 6 months prior to screening
• Receiving enteral tube feedings
• Chronic diarrheal illness unrelated to pancreatic insufficiency
• Liver abnormalities, or liver or lung transplant, or significant bowel resection
• Forced expiratory volume in 1 second (FEV1) <30%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liprotamase; Individually-optimized dose to be administered orally	Drug: Liprotamase; oral, soluble, non-enterically coated, non-porcine, pancreatic enzyme replacement
Active Comparator: porcine (pig) PERT; Individually-optimized dose to be administered orally	Drug: porcine (pig) PERT; oral, enterically-coated, pancreatic replacement enzymes prepared from a porcine source

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Difference in Coefficient of Fat Absorption (CFA) Change From Baseline	The primary endpoint evaluates the difference between treatment arms in change from baseline in coefficient of fat absorption (CFA). As such, descriptive statistics for individual treatment arms are not provided in this measure, but are reported in the secondary endpoints	Baseline, 7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coefficient of Fat Absorption (CFA)	Change from baseline in coefficient of fat absorption	Baseline, 7 weeks
Coefficient of Nitrogen Absorption (CNA)	Change from baseline in coefficient of nitrogen absorption	Baseline, 7 weeks

Collaborators and Investigators

• Sponsor: Anthera Pharmaceuticals
• Investigators: Study Director: Monica Gangal, Anthera Pharmaceuticals

Publications and helpful links

General Publications

• Somaraju URR, Solis-Moya A. Pancreatic enzyme replacement therapy for people with cystic fibrosis. Cochrane Database Syst Rev. 2020 Aug 5;8(8):CD008227. doi: 10.1002/14651858.CD008227.pub4.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): January 20, 2017

Study Registration Dates

• First Submitted: October 28, 2014
• First Submitted That Met QC Criteria: October 28, 2014
• First Posted (Estimate): October 31, 2014

Study Record Updates

• Last Update Posted (Actual): August 14, 2018
• Last Update Submitted That Met QC Criteria: July 17, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Exocrine Pancreatic Insufficiency
• Other Study ID Numbers: AN-EPI3331