Cystic Fibrosis, Exocrine Pancreatic Insufficiency
Conditions
Brief summary
Some cystic fibrosis patients are unable to digest food and absorb nutrition appropriately as they have a condition known as exocrine pancreatic insufficiency (EPI). Currently, these patients take pancreatic enzymes that are obtained from pig pancreas to aid the digestion of food. The goals of this clinical study are to evaluate the safety and efficacy of a novel formulation of a non-porcine lipase, called adrulipase, in patients with EPI due to cystic fibrosis. The main question\[s\] the study aims to answer are: 1. Is the novel formulation of adrulipase safe to use at the doses being evaluated in the clinical study. 2. Is adrulipase as effective, or more effective, compared to the pig enzymes the patients currently use. Researchers will compare the results obtained with adrulipase to how the patients typically respond to their pig enzymes to see if adrulipase helps patients digest fats adequately and if their stomach feels good (signs and symptoms of malabsorption).
Detailed description
This is an Phase 2, open label, single arm pilot study assessing the safety and efficacy of adrulipase in an enteric microgranule formulation. Patients with a confirmed diagnosis of cystic fibrosis who are 18 years of age or greater will be screened for eligibility if they have been clinically controlled on a stable dose of commercial pancreatic enzyme replacement therapy (PERT) for at least one month. Patients on cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies must have been on a stable dose for at least 3 months prior to study entry, and no dose changes will be made during the study. Patients receiving gastric acid suppressants must have been on a stable dose for at least one month prior to study entry and no dose changes will be made during the study. Upon obtaining an informed consent, potentially eligible patients will receive dietary counselling during the week prior to the scheduled date of confinement for collecting stool samples for calculation of baseline coefficient of fat absorption (CFA). This counselling will emphasize the importance of dietary stability during the study. Patients found to have a CFA of 80% or greater while receiving their commercial PERT and meeting the other eligibility criteria will be enrolled into the study. Upon study enrolment, the patient will be switched from their commercial PERT to receive adrulipase. The patient will remain on study for approximately three weeks, after which a repeat CFA will be obtained. A dose titration scheme will be used for determining whether a low, medium, or high dose of adrulipase may succeed in controlling signs and symptoms of exocrine pancreatic insufficiency (EPI) and provide a CFA of 80% or greater. Patients will initially receive a low dose of adrulipase. Upon the appearance of EPI symptoms, lasting at least three days, and upon discussion with the investigator, the patient will be switched to the medium dose of adrulipase. If signs and symptoms of EPI persist for three or more days, the patient will be switched to the high dose of adrulipase. After patients reach 3 weeks of study and complete their end of study CFA, they will be returned to their pre-study commercial PERT. An end of study safety visit will be scheduled for one week after finishing adrulipase therapy. Safety assessments will be made by collecting adverse events, safety lab assessments, and immunologic assays to assess drug induced immune responses.
Interventions
DRUGadrulipase
Enteric microgranule formulation of adrulipase.
Sponsors
Entero Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. A confirmed diagnosis of cystic fibrosis, based on 2 clinical features consistent with CF, plus either a new/historic sweat chloride \>60 mmol/L by quantitative pilocarpine iontophoresis (measured while not on a CFTR modulator) or genotype. 2. On stable dose of porcine PERT ≥1 month (30 days) prior to screening; stable dose is defined as dose of medication not changed during this time period, and the medication must be commercially available and be administered in the recommended dose range. 3. CFA = or \> 80% at screening while on stable PERT 4. A fair or better nutritional status as defined by: * BMI ≥16.0 kg/m2 for female patients ≥18 years of age, or * BMI ≥16.5 kg/m2 for male patients ≥18 years of age 5. Fecal elastase \<100 µg/g of stool at screening 6. 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 Screening 4. Feeding via an enteral tube during 6 months before screening 5. Forced expiratory volume ≤30% at the Screening visit 6. Changes in gastric acid suppressant therapy during the one month prior to screening for patients already on suppressant therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Adrulipase | End of 3-week treatment period. | Number of subjects reporting 1 or more adverse events. |
| Efficacy of Adrulipase: Coefficient of Fat Absorption (CFA) | End of 3-week treatment period. | The primary efficacy endpoint is the CFA that will be assessed at the end of the 3-week treatment period. CFAs for adrulipase will be compared to the CFAs of PERT obtained at baseline/eligibility using descriptive methods. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stool Weight | Change between two time points: initial PERT confinement and end of 3-week treatment period. | Stool weights obtained during the supervised confinement visit at the end of the 3-week treatment period will be measured. Stool weights obtained during confinement on adrulipase will be compared to the stool weights during confinement on PERT obtained at baseline/eligibility using descriptive methods. |
| Coefficient of Nitrogen Absorption (CNA) | Change between two time points: initial PERT confinement and end of 3-week treatment period | CNA that will be assessed at the end of the 3-week treatment period. CNAs for adrulipase will be compared to the CNAs of PERT obtained at baseline/eligibility using descriptive methods. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adrulipase Upon study enrolment, the patient will be switched from their commercial PERT to receive adrulipase. Patients will initially receive a low dose of adrulipase. Upon the appearance of EPI symptoms, lasting at least three days, and upon discussion with the investigator, the patient will be switched to the medium dose of adrulipase. If signs and symptoms of EPI persist for three or more days, the patient will be switched to the high dose of adrulipase.
adrulipase: Enteric microgranule formulation of adrulipase. | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Adrulipase |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age, Continuous | 33.2 years STANDARD_DEVIATION 9.86 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 5 | 0 / 7 |
| other Total, other adverse events | 0 / 1 | 2 / 5 | 0 / 7 |
| serious Total, serious adverse events | 0 / 1 | 0 / 5 | 0 / 7 |
Outcome results
Primary
Efficacy of Adrulipase: Coefficient of Fat Absorption (CFA)
The primary efficacy endpoint is the CFA that will be assessed at the end of the 3-week treatment period. CFAs for adrulipase will be compared to the CFAs of PERT obtained at baseline/eligibility using descriptive methods.
Time frame: End of 3-week treatment period.
Population: Number of participants that achieved a CFA \>= 80%
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adrulipase | Efficacy of Adrulipase: Coefficient of Fat Absorption (CFA) | 2 Participants |
Primary
Safety of Adrulipase
Number of subjects reporting 1 or more adverse events.
Time frame: End of 3-week treatment period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adrulipase | Safety of Adrulipase | 2 Participants |
Secondary
Coefficient of Nitrogen Absorption (CNA)
CNA that will be assessed at the end of the 3-week treatment period. CNAs for adrulipase will be compared to the CNAs of PERT obtained at baseline/eligibility using descriptive methods.
Time frame: Change between two time points: initial PERT confinement and end of 3-week treatment period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adrulipase | Coefficient of Nitrogen Absorption (CNA) | -27.8 Percentage of nitrogen absorbed | Standard Deviation 14.47 |
Secondary
Stool Weight
Stool weights obtained during the supervised confinement visit at the end of the 3-week treatment period will be measured. Stool weights obtained during confinement on adrulipase will be compared to the stool weights during confinement on PERT obtained at baseline/eligibility using descriptive methods.
Time frame: Change between two time points: initial PERT confinement and end of 3-week treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adrulipase | Stool Weight | 647.1 grams | Standard Deviation 496.41 |