Cystic Fibrosis (CF), Exocrine Pancreatic Insufficiency (EPI)
Conditions
Keywords
Exocrine Pancreatic Insufficiency, EPI, Cystic Fibrosis, CF
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.
Interventions
DRUGMS1819
MS1819 in enteric capsules. It contains is a yeast-derived (non-porcine) lipase pancreatic enzyme replacement.
DRUGPorcine PERT
Porcine PERT is being used a comparator to MS1819 as a second drug/intervention.
Sponsors
Entero Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
2, 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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of MS1819 by Number of Subjects Reporting 1 or More Adverse Events | Each 3-week treatment period (crossover period) and 2-week treatment period (Extension period) | Number of subjects reporting 1 or more adverse events |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stool Weights | Each 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. |
Countries
Poland, United States
Participant flow
Pre-assignment details
Patients in extension arms only included patients who were already part of the initial phase of the study.
Participants by arm
| Arm | Count |
|---|---|
| MS1819 (2240 mg/Day)-PERT Treatment Sequence Patients were randomized to MS1819 (2240 mg/day) first and then PERT. | 6 |
| PERT-MS1819 (2240 mg/Day) Sequence Patients were randomized to PERT first and then MS1819 (2240 mg/day). | 7 |
| MS1819 (4480 mg/Day)-PERT Treatment Sequence Patients were first randomized to MS1819 (4480 mg/day) and then PERT. | 5 |
| PERT-MS1819 (4480 mg/Day) Treatment Sequence Patients were first randomized to PERT and then MS1819 (4480 mg/day) | 7 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Crossover First and Second Interventions | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 |
| Crossover First and Second Interventions | Withdrawal by Subject | 1 | 1 | 0 | 0 | 0 | 0 |
| Extension Phase | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | MS1819 (2240 mg/Day)-PERT Treatment Sequence | PERT-MS1819 (2240 mg/Day) Sequence | MS1819 (4480 mg/Day)-PERT Treatment Sequence | PERT-MS1819 (4480 mg/Day) Treatment Sequence | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 7 Participants | 5 Participants | 7 Participants | 25 Participants |
| Age, Continuous | 25.2 Years STANDARD_DEVIATION 6.5 | 27.7 Years STANDARD_DEVIATION 4.1 | 27.4 Years STANDARD_DEVIATION 10.3 | 29.3 Years STANDARD_DEVIATION 4.3 | 27.3 Years STANDARD_DEVIATION 1.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 7 Participants | 5 Participants | 7 Participants | 24 Participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 4 Participants | 4 Participants | 12 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 1 Participants | 3 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 13 | 0 / 13 | 0 / 12 | 0 / 9 | 0 / 8 |
| other Total, other adverse events | 1 / 14 | 0 / 13 | 2 / 13 | 0 / 12 | 2 / 9 | 2 / 8 |
| serious Total, serious adverse events | 0 / 14 | 0 / 13 | 0 / 13 | 0 / 12 | 0 / 9 | 0 / 8 |
Outcome results
Primary
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.
Time frame: 6 weeks for crossover phase (to complete both first and second intervention) and 2 weeks for extension phase.
Population: Modified intent to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MS1819 (2240 mg/Day) | Efficacy of MS1819: Coefficient of Fat Absorption (CFA) | 66 percentage of fat absorption | Standard Deviation 19.1 |
| PERT ( MS1819 2240 mg/Day Crossover Group) | Efficacy of MS1819: Coefficient of Fat Absorption (CFA) | 83.3 percentage of fat absorption | Standard Deviation 13.1 |
| MS1819 (4480 mg/Day) | Efficacy of MS1819: Coefficient of Fat Absorption (CFA) | 52.8 percentage of fat absorption | Standard Deviation 19.4 |
| PERT (MS1819 4480 mg/Day Crossover Group) | Efficacy of MS1819: Coefficient of Fat Absorption (CFA) | 89.3 percentage of fat absorption | Standard Deviation 4.7 |
| Extension MS1819 IR (4.4 g/Day) | Efficacy of MS1819: Coefficient of Fat Absorption (CFA) | 52.9 percentage of fat absorption | Standard Deviation 12.3 |
| Extension MS1819 (6.7 g/Day) | Efficacy of MS1819: Coefficient of Fat Absorption (CFA) | 50.6 percentage of fat absorption | Standard Deviation 9.2 |
Primary
Safety of MS1819 by Number of Subjects Reporting 1 or More Adverse Events
Number of subjects reporting 1 or more adverse events
Time frame: Each 3-week treatment period (crossover period) and 2-week treatment period (Extension period)
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MS1819 (2240 mg/Day) | Safety of MS1819 by Number of Subjects Reporting 1 or More Adverse Events | 1 Participants |
| PERT ( MS1819 2240 mg/Day Crossover Group) | Safety of MS1819 by Number of Subjects Reporting 1 or More Adverse Events | 0 Participants |
| MS1819 (4480 mg/Day) | Safety of MS1819 by Number of Subjects Reporting 1 or More Adverse Events | 2 Participants |
| PERT (MS1819 4480 mg/Day Crossover Group) | Safety of MS1819 by Number of Subjects Reporting 1 or More Adverse Events | 0 Participants |
| Extension MS1819 IR (4.4 g/Day) | Safety of MS1819 by Number of Subjects Reporting 1 or More Adverse Events | 2 Participants |
| Extension MS1819 (6.7 g/Day) | Safety of MS1819 by Number of Subjects Reporting 1 or More Adverse Events | 2 Participants |
Secondary
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.
Time frame: Each 3-week treatment period (crossover period) and 2-week treatment period (Extension period)
Population: modified intent to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MS1819 (2240 mg/Day) | Coefficient of Nitrogen Absorption (CNA) | 94.4 percentage of nitrogen absorption | Standard Deviation 3.3 |
| PERT ( MS1819 2240 mg/Day Crossover Group) | Coefficient of Nitrogen Absorption (CNA) | 97.3 percentage of nitrogen absorption | Standard Deviation 1.8 |
| MS1819 (4480 mg/Day) | Coefficient of Nitrogen Absorption (CNA) | 90.9 percentage of nitrogen absorption | Standard Deviation 3.9 |
| PERT (MS1819 4480 mg/Day Crossover Group) | Coefficient of Nitrogen Absorption (CNA) | 97.5 percentage of nitrogen absorption | Standard Deviation 1 |
| Extension MS1819 IR (4.4 g/Day) | Coefficient of Nitrogen Absorption (CNA) | 93.1 percentage of nitrogen absorption | Standard Deviation 2.4 |
| Extension MS1819 (6.7 g/Day) | Coefficient of Nitrogen Absorption (CNA) | 92.6 percentage of nitrogen absorption | Standard Deviation 2.5 |
Secondary
Stool Weights
The relative efficacy of MS1819 compared to porcine PERT will be assessed using stool weights.
Time frame: Each 3-week treatment period (crossover period) and 2-week treatment period (Extension period)
Population: modified intent to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MS1819 (2240 mg/Day) | Stool Weights | 1086.9 grams | Standard Deviation 609.2 |
| PERT ( MS1819 2240 mg/Day Crossover Group) | Stool Weights | 664.4 grams | Standard Deviation 361.1 |
| MS1819 (4480 mg/Day) | Stool Weights | 1689.6 grams | Standard Deviation 681.8 |
| PERT (MS1819 4480 mg/Day Crossover Group) | Stool Weights | 644.7 grams | Standard Deviation 310.1 |
| Extension MS1819 IR (4.4 g/Day) | Stool Weights | 1301.6 grams | Standard Deviation 478.7 |
| Extension MS1819 (6.7 g/Day) | Stool Weights | 1409.3 grams | Standard Deviation 448 |