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

Phase 2

Completed

• Conditions: Exocrine Pancreatic Insufficiency (EPI); Cystic Fibrosis (CF)
• Interventions: Drug: MS1819; Drug: Porcine PERT

• Registration Number: NCT03746483
• Lead Sponsor: Entero Therapeutics

Brief Summary

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).

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 Timeline

• Study First Submitted: 2018-11-15
• Study First Submitted QC: 2018-11-16
• Study First Posted: 2018-11-19
• Study Start: 2019-01-10
• Primary Completion: 2019-07-13
• Study Completion: 2019-07-27
• Status Verified: 2020-02
• Results First Submitted: 2022-03-04
• Results First Submitted QC: 2022-05-12
• Last Update Submitted: 2022-05-12
• Results First Posted: 2022-06-06
• Last Update Posted: 2022-06-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
MS1819 2240 mg/day (3 weeks) then PERT pre-study dose (3 weeks)	Porcine PERT	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.
PERT pre-study dose(3 weeks) then MS1819 2240 mg/day (3 weeks)	MS1819	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.
PERT pre-study dose(3 weeks) then MS1819 2240 mg/day (3 weeks)	Porcine PERT	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.
MS1819 2240 mg/day (3 weeks) then PERT pre-study dose (3 weeks)	MS1819	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.

Primary Outcome Measures

Name	Time	Method
Efficacy of MS1819-SD: Coefficient of Fat Absorption (CFA)	3 weeks	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.
Safety of MS1819-SD by Number of Participants Reporting 1 or More Adverse Events (AE)	6 weeks	Number of participants reporting 1 or more adverse events
Safety of MS1819-SD by Number of Treatment Emergent Adverse Events (TEAEs)	6 weeks	Number of Treatment emergent adverse events

Secondary Outcome Measures

Name	Time	Method
Stool Weights	6 weeks	The relative efficacy of MS1819-SD compared to porcine PERT will be assessed using stool weights
Signs and Symptoms of Malabsorption	3 weeks	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.
Coefficient of Nitrogen Absorption (CNA)	3 weeks per group.	CNA at the end of each treatment period was expressed as the percentage of nitrogen (protein) absorbed from the subjects diet.

Trial Locations

Locations (14)

Investigator Site 105; 🇺🇸 Long Beach, California, United States

Investigator Site 102; 🇺🇸 Altamonte Springs, Florida, United States

Investigator Site 108; 🇺🇸 Portland, Maine, United States

Investigator Site 103; 🇺🇸 Las Vegas, Nevada, United States

Investigator Site 106; 🇺🇸 Hershey, Pennsylvania, United States

Investigator Site 202; 🇵🇱 Rabka-Zdrój, Poland

Investigator Site 107; 🇺🇸 Miami, Florida, United States

Investigator Site 203; 🇵🇱 Karpacz, Poland

Investigator Site 104; 🇺🇸 Toledo, Ohio, United States

Investigator Site 204; 🇵🇱 Sopot, Poland

Investigator Site 109; 🇺🇸 Dallas, Texas, United States

Investigator Site 101; 🇺🇸 Glenview, Illinois, United States

Investigator Site 111; 🇺🇸 Wichita, Kansas, United States

Investigator Site 110; 🇺🇸 Cleveland, Ohio, United States