OPTION: A Trial to Assess the Safety & Efficacy of MS1819 in Patients With Exocrine Pancreatic Insufficiency Due to Cystic Fibrosis (OPTION)

A Phase 2, Open-Label, Multicenter, 2x2 Crossover Trial to Assess the Safety and Efficacy of MS1819-SD in Patients With Exocrine Pancreatic Insufficiency Due to Cystic Fibrosis

The primary objectives of this study are to assess the safety and efficacy of MS1819-SD vs porcine pancreatic enzyme replacement therapy (PERT) in patients with exocrine pancreatic insufficiency (EPI) due to cystic fibrosis (CF).

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis (CF); Exocrine Pancreatic Insufficiency (EPI)
• Intervention / Treatment: Drug: MS1819; Drug: Porcine PERT

Detailed Description

This is a Phase 2, open-label, multi-center, 2x2 crossover study assessing the safety and efficacy of MS1819-SD (spray dried) vs porcine PERT given at the same dose that was being administered during the pre-study period.

MS1819-SD will be assessed in a 2x2 crossover including at least 30 patients completing both periods.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• Poland
  • Karpacz, Poland
    • Investigator site 203
  • Rabka-Zdrój, Poland
    • Investigator site 202
  • Sopot, Poland
    • Investigator site 204
• United States
  • California
    • Long Beach, California, United States, 90806
      • Investigator site 105
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Investigator site 102
    • Miami, Florida, United States, 33136
      • Investigator site 107
  • Illinois
    • Glenview, Illinois, United States, 60025
      • Investigator site 101
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Investigator site 111
  • Maine
    • Portland, Maine, United States, 04102
      • Investigator site 108
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Investigator site 103
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Investigator site 110
    • Toledo, Ohio, United States, 43606
      • Investigator site 104
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Investigator site 106
  • Texas
    • Dallas, Texas, United States, 75235
      • Investigator site 109

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Cystic fibrosis, based on 2 clinical features consistent with CF, plus initial diagnostic sweat chloride ≥ 60 mmol/L
2. Under stable dose of porcine PERT
3. A fair or better nutritional status
4. Fecal elastase <100 µg/g
5. Standard-of-care medications including Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators are allowed

Exclusion Criteria:

1. History or diagnosis of fibrosing colonopathy
2. Any chronic diarrheal illness unrelated to pancreatic insufficiency
3. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥5 ×upper limit of normal (ULN), or total bilirubin level ≥1.5 ×ULN at the Screening visit
4. Feeding via an enteral tube during 6 months before screening
5. Forced expiratory volume ≤30% at the Screening visit

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MS1819 2240 mg/day (3 weeks) then PERT pre-study dose (3 weeks); Patients in arm will further be randomized to receive either the sequence consisting of MS1819 2240 mg/day for 3 weeks followed by PERT for another 3 weeks. During the PERT treatment period the patients will take their stable pre-study PERT dose.	Drug: MS1819; MS1819, an oral, non-systemic, that is non-enterically-coated. It is a yeast-derived (non-porcine) lipase pancreatic enzyme replacement.; Drug: Porcine PERT; Porcine PERT is being used as a comparator to MS1819 as a second drug/intervention
Experimental: PERT pre-study dose(3 weeks) then MS1819 2240 mg/day (3 weeks); Patients in arm will be randomized to receive PERT for 3 weeks followed by MS1819 2240 mg/day for another 3 weeks. During the PERT treatment period the patients will take their stable pre-study PERT dose.	Drug: MS1819; MS1819, an oral, non-systemic, that is non-enterically-coated. It is a yeast-derived (non-porcine) lipase pancreatic enzyme replacement.; Drug: Porcine PERT; Porcine PERT is being used as a comparator to MS1819 as a second drug/intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of MS1819-SD: Coefficient of Fat Absorption (CFA)	The Coefficient of Fat Absorption (CFA%) is defined as: [72-hour fat intake (g) - 72-hour fat excretion (g)/72-hour fat intake(g)] x 100 = CFA% The threshold for CFA results (>80%) is considered clinically significant for treatment effectiveness by the FDA.	3 weeks
Safety of MS1819-SD by Number of Participants Reporting 1 or More Adverse Events (AE)	Number of participants reporting 1 or more adverse events	6 weeks
Safety of MS1819-SD by Number of Treatment Emergent Adverse Events (TEAEs)	Number of Treatment emergent adverse events	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stool Weights	The relative efficacy of MS1819-SD compared to porcine PERT will be assessed using stool weights	6 weeks
Signs and Symptoms of Malabsorption	The relative efficacy of MS1819 compared to porcine PERT will be assessed using signs and symptoms of malabsorption. Abdominal pain, bloating, flatulence, increased stool quantity, and worsening of overall bowel habit were graded as 0 = none, 1 = mild, 2 = moderate, or 3 = severe.	3 weeks
Coefficient of Nitrogen Absorption (CNA)	CNA at the end of each treatment period was expressed as the percentage of nitrogen (protein) absorbed from the subjects diet.	3 weeks per group.

Collaborators and Investigators

• Sponsor: First Wave Bio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2019
• Primary Completion (Actual): July 13, 2019
• Study Completion (Actual): July 27, 2019

Study Registration Dates

• First Submitted: November 15, 2018
• First Submitted That Met QC Criteria: November 16, 2018
• First Posted (Actual): November 19, 2018

Study Record Updates

• Last Update Posted (Actual): June 6, 2022
• Last Update Submitted That Met QC Criteria: May 12, 2022
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; CF; Lipase; EPI; Exocrine pancreatic insufficiency; Pancreatic enzyme replacement therapy (PERT)
• 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: AZ-CF2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No