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OPTION 2: A Trial to Assess the Safety and Efficacy of MS1819 in Enteric Capsules in Patients With Cystic Fibrosis

Phase 2
Completed
Conditions
Exocrine Pancreatic Insufficiency (EPI)
Cystic Fibrosis (CF)
Interventions
Drug: Porcine PERT
Registration Number
NCT04375878
Lead Sponsor
Entero Therapeutics
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
27
Inclusion Criteria
  1. 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.
  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 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
GroupInterventionDescription
MS1819 2240 mg/day vs PERT arm,MS1819Patients 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.
MS1819 2240 mg/day vs PERT arm,Porcine PERTPatients 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.
MS1819 4480 mg/day vs PERT armMS1819Patients 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.
MS1819 4480 mg/day vs PERT armPorcine PERTPatients 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.
Primary Outcome Measures
NameTimeMethod
Efficacy of MS1819: Coefficient of Fat Absorption (CFA)6 weeks for crossover phase (to complete both first and second intervention) and 2 weeks for extension phase.

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.

Safety of MS1819 by Number of Subjects Reporting 1 or More Adverse EventsEach 3-week treatment period (crossover period) and 2-week treatment period (Extension period)

Number of subjects reporting 1 or more adverse events

Secondary Outcome Measures
NameTimeMethod
Stool WeightsEach 3-week treatment period (crossover period) and 2-week treatment period (Extension period)

The relative efficacy of MS1819 compared to porcine PERT will be assessed using stool weights.

Coefficient of Nitrogen Absorption (CNA)Each 3-week treatment period (crossover period) and 2-week treatment period (Extension period)

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.

Trial Locations

Locations (15)

Investigator Site 102

🇺🇸

Altamonte Springs, Florida, United States

Investigator Site 111

🇺🇸

Wichita, Kansas, United States

Investigator Site 106

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Hershey, Pennsylvania, United States

Investigator Site 205

🇵🇱

Białystok, Poland

Investigator Site 107

🇺🇸

Miami, Florida, United States

Investigator Site 206

🇵🇱

Katowice, Poland

Investigator Site 105

🇺🇸

Long Beach, California, United States

Investigator Site 110

🇺🇸

Cleveland, Ohio, United States

Investigator Site 101

🇺🇸

Glenview, Illinois, United States

Investigator Site 108

🇺🇸

Portland, Maine, United States

Investigator Site 104

🇺🇸

Toledo, Ohio, United States

Investigator Site 204

🇵🇱

Sopot, Poland

Investigator Site 203

🇵🇱

Karpacz, Poland

Investigator Site 202

🇵🇱

Rabka-Zdrój, Poland

Investigator Site 103

🇺🇸

Las Vegas, Nevada, United States

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