A Phase 3, Open-Label Study Evaluating the Efficacy and Safety of Liprotamase in Subjects with Cystic Fibrosis-Related Exocrine Pancreatic Insufficiency.
- Children’s Medical Center (Dallas, Plano, Southlake)
Meghana Sathe, M.D.
SuMMaRY oF STuDY DeSiGn:
The SiMPLiCiTY Study (an-ePi3332) is a Phase 3, open-label, study to evaluate the efficacy and safety of liprotamase in subjects with ePi due to CF. The study will be conducted in two parts. approximately 46 subjects will be enrolled between Part a and Part B.
* in Part a, approximately 16 subjects [GreaterThanorequalTo]7 years of age will be enrolled and will receive liprotamase for 1 week. Subjects enrolled in Part a must be on a stable PeRT regimen prior to study enrollment, which they will discontinue on Day 1 of the treatment period, upon initiation of open-label liprotamase administration at a dose that closely matches the lipase units of the pre-study PeRT. Safety, stool frequency, and symptoms and signs of malabsorption will be followed for the weeks of liprotamase dosing. For subjects in Part a, the total study duration will be up to 3 weeks including a screening period of up to 2 weeks.
* in Part B, approximately 30 subjects with ePi due to CF who are 28 days old to [Less Than]7 years old will be enrolled. Subjects enrolled in Part B will continue to receive pre-study PeRT (if receiving PeRT prior to enrollment) throughout the screening period and until Day 1 when they will initiate dosing with liprotamase. once enrolled, subjects will enter a 24-week dosing period with open-label liprotamase. The starting dose of liprotamase will match the dose of pre-study PeRT based on number of lipase units. Subjects [LessThanorequalTo]2 years of age who are not on a PeRT regimen prior to enrollment may initiate enzyme therapy with liprotamase in this study in accordance with the treatment guidelines of the CFF (appendix e): 2,000-5,000 u lipase at each feeding, adjusted up to a dose no greater than 2,500 u lipase/kg for each feeding with a maximum dose of 10,000 u lipase/kg/day. Subjects should maintain background medications for treatment of cystic fibrosis throughout the study, including approved potentiators or modulators of the CFTR and gastric acid suppression therapy. For measurement of CFa, the primary efficacy endpoint for Part B, subjects will be required to maintain a controlled diet, and participate in a supervised stool collection at Week 7. The period of supervised stool collection will last approximately 72 hours. For subjects in Part B, the total study duration will be up to 26 weeks including a screening period of up to 2 weeks, dosing through the evaluation of CFa at Week 7, and continued dosing to evaluate safety and additional measures of efficacy through the end of the extension Period at Week 24. Subjects who receive nutrition through breast milk may be enrolled into Part B of the study as long as nutritional intake can be accurately determined during the 5-day period of controlled diet for CFa measurement.
initiation of Part B will begin after Part a has been completed and all data have been reviewed by the DSMB, and the DSMB has deemed it is safe to proceed. The DSMB will consist of members external to the Sponsor (anthera Pharmaceuticals, inc.), and will include members of the Cystic Fibrosis Foundation Therapeutics, inc. (CFFT) DSMB. The DSMB will monitor safety throughout the trial.
The primary endpoint analysis of Part a will evaluate the safety of Liprotamase Powder for oral Solution in adults and pediatric subjects [GreaterThanorequalTo]7 years. Safety will be evaluated based on adverse events (aes) including serious aes (Saes), blood chemistry, hematology, urinalysis, physical examinations, and vital signs.
The secondary endpoints of Part a will include:
* Stool frequency compared with baseline.
* Signs and symptoms of malabsorption including stool consistency, bloating, steatorrhea, abdominal pain, and flatulence compared with baseline.
The primary endpoint analysis of Part B of this study will evaluate the efficacy of liprotamase as measured by the coefficient of fat absorption (CFa) at Week 7 in pediatric subjects 28 days to [Less Than]7 years of age with ePi due to CF.
Only subjects who meet all of the following criteria will be eligible for inclusion in Part A or Part B of this study:
* For Part A: males or females >=7 years of age at the time of screening. This number should include at least 6 subjects aged >=7 years to <17 years.
* For Part B: males or females 28 days to <7 years of age at the time of screening. Efforts will be made to enroll subjects from each of the following age groups as follows:
2. Cystic fibrosis based on the disease diagnostic criteria:
* At least one clinical feature consistent with CF, and
A. Genotype with 2 identifiable Class I x III Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutations consistent with CF, or
B. Sweat chloride >=60 mmol/L (>=60 mEq/L) by quantitative pilocarpine iontophoresis.
3. Have fecal elastase <100 mcg/g stool measured any time prior to or during screening of <100 mcg/g stool for subjects >=2 years of age, or < 200 mcg/g for subjects < 2 years of age.
4. Are clinically stable with no evidence of acute upper or lower respiratory tract infection in the 10 days prior to screening.
5.1) Have fair-to-good nutritional status at Screening, as evidenced by BMI >= 16kg/m([SQUARED] for female subjects >=18 years of age, BMI >=16.5 kg/m([SQUARED] for male subjects >= 18 years of age, BMI >= 25th percentile for subjects >=2 years of age up to 18 years of age, and >3rd percentile weight-for-age (compared with World Health Organization [WHO] weight data) for subjects < 2 years of age.
6. Have been using the same pancreatic enzyme treatment without change in dosing regimen for at least 2 weeks prior to Day 1 of the treatment period. Subjects <=2 years of age who are not on a PERT regimen prior to enrollment may initiate enzyme therapy with liprotamase in this study in accordance with the treatment guidelines of the Cystic Fibrosis Foundation (CFF, Appendix E): 2,000-5,000 U lipase at each feeding, adjusted up to a dose no greater than 2,500 U lipase/kg for each feeding with a maximum dose of 10,000 U lipase/kg/day.
7. Are able to perform testing and procedures required for the study, as judged by the Investigator.
8. If younger than 18 years of age, have a parent or legal guardian who has given written informed consent approved by Anthera or its designee and the Investigational Review Board/Independent Ethics Committee (IRB/IEC) governing the investigational site.
9. Subjects who did not meet the enrollment criteria for the SOLUTION trial (Study AN-EPI3331) may participate in in Part A of this trial as long as they meet all enrollment criteria for this trial. For these subjects, screening evaluations and procedures conducted within 1 month of screening into the SIMPLICITY trial do not need to be repeated. These subjects will be considered in consultation with the Medical Monitor on a case-by-case basis.