OPTION 2: A Trial to Assess the Safety and Efficacy of MS1819 in Enteric Capsules in Patients With 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 in enteric capsules vs porcine pancreatic enzyme replacement therapy (PERT) in patients with exocrine pancreatic insufficiency (EPI) due to cystic fibrosis (CF). The exploratory objective of the extension phase (EP) is to find a dose of MS1819 in immediate release capsules that is safe and results in CFA values in a therapeutic range.

Detailed Description
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This is a Phase 2, open-label, multicenter, 2, 2x2 crossover study assessing the safety and efficacy of MS1819, 2240 mg/day vs porcine PERT, and 4480 mg/day vs porcine PERT given at the same dose and dosing regimen that was being administered during the pre-study period. MS1819 will be administered in enteric capsules. MS1819 will be assessed in a 2x2 crossover including approximately 30 patients completing both periods. Fifteen patients will be randomized to the MS1819 2240 mg/day vs PERT arm, and 15 patients will be randomized to the MS1819 4480 mg/day vs PERT arm. Patients in each arm will further be randomized to receive either the sequence consisting of MS1819 for 3 weeks followed by PERT for another 3 weeks or the opposite sequence of treatments, PERT for 3 weeks followed by MS1819 for another 3 weeks.The coefficient of fat absorption (CFA) will be measured at the end of each 3 week study period. Patients enrolled into the extension phase (EP) will be composed of patients who have completed the crossover phase of OPTION 2.

Official Title
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OPTION 2: A Phase 2, Open-Label, Multicenter, 2x2 Crossover Trial to Assess the Safety and Efficacy of MS1819 in Enteric Capsules in Patients With Exocrine Pancreatic Insufficiency Due to Cystic Fibrosis; With an Extension Phase Evaluation of Immediate Release MS1819 Capsules

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 either a new/historic sweat chloride ≥60 mmol/L (measured while not on a CFTR modulator) or genotype. Under stable dose of porcine PERT A fair or better nutritional status Fecal elastase <100 µg/g Standard-of-care medications including 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: 2, 2x2 Crossover
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MS1819 2240 mg/day vs PERT arm,<br>Patients in arm will further be randomized to receive either the sequence consisting of MS1819 for 3 weeks followed by PERT for another 3 weeks or the opposite sequence of treatments, PERT for 3 weeks followed by MS1819 for another 3 weeks. | Drug: MS1819<br>* MS1819 in enteric capsules. It contains is a yeast-derived (non-porcine) lipase pancreatic enzyme replacement.<br>Drug: Porcine PERT<br>* Porcine PERT is being used a comparator to MS1819 as a second drug/intervention.<br>|
| Active Comparator: MS1819 4480 mg/day vs PERT arm<br>Patients in arm will further be randomized to receive either the sequence consisting of MS1819 for 3 weeks followed by PERT for another 3 weeks or the opposite sequence of treatments, PERT for 3 weeks followed by MS1819 for another 3 weeks. | Drug: MS1819<br>* MS1819 in enteric capsules. It contains is a yeast-derived (non-porcine) lipase pancreatic enzyme replacement.<br>Drug: Porcine PERT<br>* Porcine PERT is being used 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 |
| --- | --- | --- |
| Safety of MS1819 by Number of Subjects Reporting 1 or More Adverse Events | Number of subjects reporting 1 or more adverse events | Each 3-week treatment period (crossover period) and 2-week treatment period (Extension period) | 
| Efficacy of MS1819: Coefficient of Fat Absorption (CFA) | The primary efficacy endpoint is the CFA that will be assessed at the end of each 3-week treatment period (crossover period) and 2-week treatment period (Extension period). CFAs for MS1819 will be compared to the CFAs of PERT using descriptive methods. | 6 weeks for crossover phase (to complete both first and second intervention) and 2 weeks for extension phase. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stool Weights | The relative efficacy of MS1819 compared to porcine PERT will be assessed using stool weights. | Each 3-week treatment period (crossover period) and 2-week treatment period (Extension period) | 
| Coefficient of Nitrogen Absorption (CNA) | CNA that will be assessed at the end of each 3-week treatment period (crossover period) and 2-week treatment period (Extension period). CFAs for MS1819 will be compared to the CFAs of PERT using descriptive methods. CNAs for MS1819 will be compared to the CNAs of PERT using descriptive methods. | Each 3-week treatment period (crossover period) and 2-week treatment period (Extension period) | 

 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