A Randomized, Double-blind, Multicenter, Two-Period Crossover Study to Assess the Efficacy and Tolerability of NM-BL (Burlulipase) in Patients with Exocrine Pancreatic Insufficiency due to Cystic Fibrosis
This is a Phase iia, randomized, double-blind, multicenter, two-period crossover study to compare
nM-BL (Burlulipase) 360 mg nM-BL-protein/day to placebo in patients with ePi due to CF. it is
planned to randomize approximately 28 patients in order to have 22 patients completing both
Treatment Periods (11 patients in each treatment sequence). each patient is expected to
participate in the study for up to 8 weeks (this includes a Screening Period of up to 35 days, two
Treatment Periods of up to 7 days each, and an approximate 7-day Follow-up Period it
excludes the Stabilization Period between the Treatment Periods, lasting 1 to 4 weeks, when the
patient will take their normal enzyme replacement therapy at home).
a diagram of the study design is presented in Figure 1 in the protocol.
The primary efficacy variable is the:
[?] Comparison of CFa% between nM-BL and placebo Treatment Periods.
Secondary efficacy variables are the:
[?] Comparison of the following gastrointestinal parameters, recorded by the patient/carer in the
Symptom Questionnaire in the evening of each day during the Treatment Periods: stool
frequency, consistency, flatulence, and abdominal pain. The average score in each Treatment
Period will be used for the analysis.
[?] Comparison of Cna% between nM-BL and placebo Treatment Periods.
To be eligible for the study, patients must meet the following criteria:
1. Male and female patients aged >=12 years from the date of informed consent and assent, if
2. Confirmed diagnosis of CF at Screening based on the following criteria:
- Two clinical features consistent with CF at least one of the following
- Sweat test with sweat chloride >=60 mmol/L (by quantitative pilocarpine iontophoresis)
- Genotype with two identifiable mutations consistent with CF.
3. Confirmed EPI by historical (within the past 12 months) CFA <70% without the use of PERT or
by current fecal elastase <50 [MICRO-SYMBOL]g/g stool at Screening.
4. Currently receiving PERT with a commercially available pancreatic enzyme. Patients should
also be willing and able to remain on the same regimen of PERT during the Stabilization
Period of the study.
5. Nutritionally stable and acceptable BMI.
6. Currently on stable treatment or willing to start treatment with proton pump inhibitors or
H2 receptor antagonists (for at least 1 week prior to Treatment Period 1).
7. Clinically stable condition without evidence of acute respiratory disease or any other acute
condition within 30 days before Screening.
8. Females of child-bearing potential who agree to continue using a medically acceptable method
of birth control which would include:
- Double-barrier contraception such as condom with spermicidal jelly, foam suppository, or
film; diaphragm with spermicide; male condom and diaphragm; or stable dose regimen of
oral contraception and male condom;
- Complete abstinence from sexual intercourse throughout the entire study; or
- Female who has undergone a hysterectomy; or
- Vasectomized partner who is sterile before the female patient[Single Quote]s entry and is the sole sexual
partner for that female.
9. Be willing and able to comply with the clinical study protocol requirements (e.g., stool
collections, inpatient stays, high-fat diet prescribed by dietician).
10. Be able to understand and willing to provide written informed consent (patients >=18 years of
age) or assent (patients <18 years of age; as well as written informed consent signed by a
parent/legal guardian or caregiver).
Before patients can enter the double-blind part of the study they must have met all eligibility
criteria, including a current fecal elastase of <50 [MICRO-SYMBOL]g/g stool (or a historical [within the past
12 months] CFA <70% without the use of PERT).