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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Exocrine Pancreatic Insufficiency (EPI), Cystic Fibrosis (CF)

Intervention / Treatment
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* Drug: MS1819
* Drug: Porcine PERT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cystic fibrosis, based on 2 clinical features consistent with CF, plus initial diagnostic sweat chloride ≥ 60 mmol/L Under stable dose of porcine PERT A fair or better nutritional status Fecal elastase <100 µg/g Standard-of-care medications including Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators are allowed Exclusion Criteria: History or diagnosis of fibrosing colonopathy Any chronic diarrheal illness unrelated to pancreatic insufficiency 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 Feeding via an enteral tube during 6 months before screening Forced expiratory volume ≤30% at the Screening visit

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 2x2 Crossover
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MS1819 2240 mg/day (3 weeks) then PERT pre-study dose (3 weeks)<br>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<br>* MS1819, an oral, non-systemic, that is non-enterically-coated. It is a yeast-derived (non-porcine) lipase pancreatic enzyme replacement.<br>Drug: Porcine PERT<br>* Porcine PERT is being used as a comparator to MS1819 as a second drug/intervention<br>|
| Experimental: PERT pre-study dose(3 weeks) then MS1819 2240 mg/day (3 weeks)<br>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<br>* MS1819, an oral, non-systemic, that is non-enterically-coated. It is a yeast-derived (non-porcine) lipase pancreatic enzyme replacement.<br>Drug: Porcine PERT<br>* Porcine PERT is being used as a comparator to MS1819 as a second drug/intervention<br>|

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exocrine pancreatic insufficiency, EPI, Cystic Fibrosis, CF, Pancreatic enzyme replacement therapy (PERT), Lipase