A Phase 3, Randomized, Open-Label, Assessor-Blind, Non-Inferiority, Active-Comparator Study Evaluating the Efficacy and Safety of Liprotamase in Subjects with Cystic Fibrosis-Related Exocrine Pancreatic Insufficiency
Study ID: STU 022017-063
This is a Phase 3, 2-group, parallel, randomized, open-label, assessor-blind, non-inferiority study comparing the non-porcine enzyme product, liprotamase, to Pancreaze in subjects [GreaterThanorequalTo]7 years of age with ePi due to CF. * The study will be conducted as outpatient except for 2 periods of supervised confinement each lasting up to 7 days during which marker-to-marker stool samples will be collected for determination of CFa. There maybe an ad hoc in hospital stay for subject equal to or great than 17 years of age. * Following the first screening visit, subjects will continue their pre-study pancreatic enzyme therapy followed by their first supervised confinement admission for stool collection (screening Visit 2) and subsequent calculation of CFa * Subjects who meet all of the enrollment criteria will be randomized to receive liprotamase or Pancreaze. a total of approximately 150 subjects will be randomized 1:1 to Liprotamase or Pancreaze. * Subjects randomized to Pancreaze will initiate dosing at a lipase dose that match the dose of pre-study PeRT based on number of lipase units. * adjustment of the liprotamase or Pancreaze dose may occur at any time during the first 3 weeks of the Primary Treatment Period at the end of the 4-week Primary Treatment Period, subjects will have their second and final period of supervised confinement for stool collection and subsequent calculation of CFa. * after the Week 4 CFa assessments, all subjects randomized to Pancreaze will discontinue from the study and resume therapy with a commercially-available PeRT according to physician prescription. * after the Week 4 CFa assessments, all subjects randomized to liprotamase will continue, at least initially, to receive liprotamase in the extension Period. * Subjects [GreaterThanorequalTo]17 years of age who enroll into the extension Period at a liprotamase dose [LessThanorequalTo]10,000 u lipase-CLeC/kg/day may increase liprotamase dose above 10,000 u lipase-CLeC/kg/day based on investigator assessment of nutritional status, food consumption, age, weight, fat intake, and clinical signs/symptoms of malabsorption, as long as the protocol-defined maximum dose is not exceeded. in such cases, an ad hoc supervised confinement and marker-to-marker stool collection for measurement of CFa must be conducted within 1 week, if possible, and no later than 1 month after the new stable dose is reached to evaluate suitability of the new liprotamase dose. The subject may continue to receive the new, higher liprotamase dose if the ad hoc CFa is at least 80%. * an interim analysis of risk/benefit will be conducted by an independent unblinded statistician and reviewed by the independent Data Monitoring Committee when at least approximately 15 subjects randomized to liprotamase have completed the Week 4 CFa assessments. The only outcome of the interim analysis of risk/benefit will be to either stop the study for futility or continue as planned; it will not inform or enable any decision to stop the study early for efficacy. all individuals who are directly involved with the study will remain blinded to Week 4 CFa during the interim analysis. * at the end of the 20-week extension Period, the study will be complete and the subjects (randomized to liprotamase) may elect to continue to receive liprotamase by enrolling in the eaSY study (an-ePi3334). Subjects randomized to liprotamase who do not enroll in the eaSY study will resume therapy witha commercially-available PeRT according to physician prescription.
Only subjects who meet all of the following criteria will be eligible for inclusion: 1. Cystic Fibrosis based on the disease diagnostic criteria: * Two clinical features consistent with CF, and * Either: a) genotype with 2 identifiable mutations consistent with CF, or b) sweat chloride >60 mEq/L by quantitative pilocarpine iontophoresis. Diagnostic evidence of CF disease may be measured during screening unless previously documented. 2. Age >= 7 years of age at the time of screening. 3. Have fecal elastase <100 mcg/g stool measured during screening. 4. CFA during screening of >=80% while receiving PERT therapy. Subjects who meet all enrollment criteria except CFA may be re-screened for CFA after an increase in pre-enrollment PERT dose for at least 1 week if this is deemed to be safe and appropriate by the Investigator. Such rescreening of CFA should occur within 30 days of the result of the first CFA measurement. 5. Are clinically stable with no evidence of acute upper or lower respiratory tract infection in the last 10 days prior to Visit 1. 6. Are of fair or better nutritional status as defined by: * BMI >=16.0 kg/m2 for female subjects >=18 years of age, or * BMI >=16.5 kg/m2 for male subjects >=18 years of age, or * BMI >=25th percentile for subjects 7 to <18 years of age based on growth charts published by the World Health organization (WHO). * Weight for all age groups has remained stable (no more than a 5% decline) during the 90 days prior to screening. 7. Are able to take pancreatic enzyme supplementation in the form of capsules. 8. Using the same pancreatic enzyme treatment for the past 30 days without change in dosing regimen unless the change in regimen occurs during CFA rescreening as described in the Inclusion Criterion #4. 9. Subjects receiving gastric acid suppression therapy (proton pup inhibitor or histamine antagonist) must have been on a stable dose for at least 30 days prior to Visit 2. 10. Are able to perform testing and procedures required for the study, as judged by the Investigator. 11. If adult, have given written informed consent or assent as required by Anthera or its designee and the Institutional Review Board/Independent Ethic Committee (IRB/IEC). If not adult, have parent or legal guardian who has given written informed consent approved by Anthera or its designee and the IRB/IEC governing the site.
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- Meghana Nitin Sathe
ANTHERA PHARMACEUTICALS INC