Cystic Fibrosis (CF), Exocrine Pancreatic Insufficiency (EPI)
Conditions
Keywords
Exocrine pancreatic insufficiency, EPI, Cystic Fibrosis, CF, Pancreatic enzyme replacement therapy (PERT), Lipase
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.
Interventions
DRUGMS1819
MS1819, an oral, non-systemic, that is non-enterically-coated. It is a yeast-derived (non-porcine) lipase pancreatic enzyme replacement.
DRUGPorcine PERT
Porcine PERT is being used as a comparator to MS1819 as a second drug/intervention
Sponsors
Entero Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Masking description
Unblinded
Intervention model description
2x2 Crossover
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Poland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MS1819 - PERT Sequence Participants were first randomized to receive MS1819 first and PERT during the crossover phase | 17 |
| PERT - MS1819 Sequence Participants were first randomized to receive PERT first and MS1819 during the crossover phase | 19 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lack of Efficacy | 3 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 2 | 0 |
Baseline characteristics
| Characteristic | MS1819 - PERT Sequence | PERT - MS1819 Sequence | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 19 Participants | 36 Participants |
| Age, Continuous | 28.5 years STANDARD_DEVIATION 7.6 | 29.0 years STANDARD_DEVIATION 7.97 | 28.8 years STANDARD_DEVIATION 7.69 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 19 Participants | 35 Participants |
| Region of Enrollment Poland | 4 participants | 6 participants | 10 participants |
| Region of Enrollment United States | 13 participants | 13 participants | 26 participants |
| Sex: Female, Male Female | 4 Participants | 11 Participants | 15 Participants |
| Sex: Female, Male Male | 13 Participants | 8 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 38 |
| other Total, other adverse events | 13 / 40 | 6 / 38 |
| serious Total, serious adverse events | 0 / 40 | 0 / 38 |
Outcome results
Primary
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.
Time frame: 3 weeks
Population: modified Intent To Treat (mITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MS1819 | Efficacy of MS1819-SD: Coefficient of Fat Absorption (CFA) | 55.6 % CFA | Standard Deviation 21.44 |
| PERT | Efficacy of MS1819-SD: Coefficient of Fat Absorption (CFA) | 86.2 % CFA | Standard Deviation 7.39 |
Primary
Safety of MS1819-SD by Number of Participants Reporting 1 or More Adverse Events (AE)
Number of participants reporting 1 or more adverse events
Time frame: 6 weeks
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MS1819 | Safety of MS1819-SD by Number of Participants Reporting 1 or More Adverse Events (AE) | Number of subjects with any TEAEs | 13 Participants |
| MS1819 | Safety of MS1819-SD by Number of Participants Reporting 1 or More Adverse Events (AE) | Number of subjects with TEAEs related to | 2 Participants |
| PERT | Safety of MS1819-SD by Number of Participants Reporting 1 or More Adverse Events (AE) | Number of subjects with any TEAEs | 6 Participants |
| PERT | Safety of MS1819-SD by Number of Participants Reporting 1 or More Adverse Events (AE) | Number of subjects with TEAEs related to | 0 Participants |
Primary
Safety of MS1819-SD by Number of Treatment Emergent Adverse Events (TEAEs)
Number of Treatment emergent adverse events
Time frame: 6 weeks
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MS1819 | Safety of MS1819-SD by Number of Treatment Emergent Adverse Events (TEAEs) | Number of Treatment-emergent adverse event (TEAEs) | 19 Number of TEAEs reported |
| MS1819 | Safety of MS1819-SD by Number of Treatment Emergent Adverse Events (TEAEs) | Number of serious TEAEs reported | 0 Number of TEAEs reported |
| PERT | Safety of MS1819-SD by Number of Treatment Emergent Adverse Events (TEAEs) | Number of Treatment-emergent adverse event (TEAEs) | 8 Number of TEAEs reported |
| PERT | Safety of MS1819-SD by Number of Treatment Emergent Adverse Events (TEAEs) | Number of serious TEAEs reported | 0 Number of TEAEs reported |
Secondary
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.
Time frame: 3 weeks per group.
Population: mITT. Samples from 4 patients were not available for analysis due to discontinuation from the study. Three patients discontinued in the MS1819 group while 1 patient discontinued in the PERT group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MS1819 | Coefficient of Nitrogen Absorption (CNA) | 93.0 % CNA | Standard Deviation 2.54 |
| PERT | Coefficient of Nitrogen Absorption (CNA) | 97.2 % CNA | Standard Deviation 1.21 |
Secondary
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.
Time frame: 3 weeks
Population: Data presented at 3 weeks post first dose.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MS1819 | Signs and Symptoms of Malabsorption | Grade 3 | 1 Participants |
| MS1819 | Signs and Symptoms of Malabsorption | Unknown | 2 Participants |
| MS1819 | Signs and Symptoms of Malabsorption | Grade 1 | 12 Participants |
| MS1819 | Signs and Symptoms of Malabsorption | Grade 0 | 15 Participants |
| MS1819 | Signs and Symptoms of Malabsorption | Grade 2 | 6 Participants |
| PERT | Signs and Symptoms of Malabsorption | Grade 2 | 1 Participants |
| PERT | Signs and Symptoms of Malabsorption | Grade 3 | 0 Participants |
| PERT | Signs and Symptoms of Malabsorption | Grade 0 | 32 Participants |
| PERT | Signs and Symptoms of Malabsorption | Unknown | 0 Participants |
| PERT | Signs and Symptoms of Malabsorption | Grade 1 | 3 Participants |
Secondary
Stool Weights
The relative efficacy of MS1819-SD compared to porcine PERT will be assessed using stool weights
Time frame: 6 weeks
Population: mITT. Samples from 4 patients were not available for analysis due to discontinuation from the study. Three patients discontinued in the MS1819 group while 1 patient discontinued in the PERT group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MS1819 | Stool Weights | 1394.0 grams | Standard Deviation 590.63 |
| PERT | Stool Weights | 727.3 grams | Standard Deviation 334.29 |