Cellcept for Treatment of Juvenile Neuronal Ceroid Lipofuscinosis (JUMP)
The primary objective of this trial is to establish the safety and tolerability of short-term (8 weeks) administration of mycophenolate mofetil in ambulatory children with JNCL. The secondary objective is to gather preliminary evidence of the short-term (8 week) impact of mycophenolate mofetil on clinically relevant features of JNCL as measured by the Unified Batten Disease Rating Scale (UBDRS), including motor features, seizures, behavior, cognitive and functional measures.
Funding source-FDA Office of Orphan Product Development (OOPD).
Juvenile Neuronal Ceroid Lipofuscinosis
Drug: Mycophenolate mofetil
Drug: Liquid Placebo
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Phase II, Randomized, Placebo Controlled Trial of the Safety and Tolerability of Mycophenolate in Children With Juvenile Neuronal Ceroid Lipofuscinosis|
- Tolerability [ Time Frame: 8 weeks ]The primary outcome measure is tolerability, defined as the completion of 8 weeks on the assigned dosage of study drug.
- Preliminary Evidence of Efficacy [ Time Frame: 8 week ]To gather preliminary evidence of the short-term (8 week) impact of mycophenolate mofetil on clinically relevant features of Juvenile Neuronal Ceroid Lipofuscinosis as measured by the Unified Batten Disease Rating Scale, including motor features, seizures, behavior, cognitive and functional measures.
- Feasibility of Clinical Trials in Rare DisorderTo pilot the feasibility of conducting controlled clinical trials of this rare neurological disorder base on collaboration between a national center of excellence in the disease (URBC), and children's local care-providers (pediatricians and/or local neurologists.
|Study Start Date:||July 2011|
|Study Completion Date:||November 2015|
|Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
|Active Comparator: Mycophenolate Mofetil||
Drug: Mycophenolate mofetil
The liquid dosage will be individualized, contingent upon the subject's weight. Subjects will receive 50% of the target dose (300mg/m2/dose BID) during Week 0-Week 2, then increase to the full dose (600mg/m2/dose BID) in Week 3, continuing at this dose through Week 8. Additionally, due to the risk of gastrointestinal disturbance (hemorrhage, ulcer), children will also receive prophylactic Prilosec (Omeprazole) for the duration of the study, during both the mycophenolate and placebo arms.
Other Name: Cellcept
|Placebo Comparator: Placebo liquid||
Drug: Liquid Placebo
The dosage will be individualized, contingent upon the subject's weight. Subjects will receive 50% of the target dose (300mg/m2/dose BID) during Week 0-Week 2, then increase to the full dose (600mg/m2/dose BID) in Week 3, continuing at this dose through Week 8. Additionally, due to the risk of gastrointestinal disturbance (hemorrhage, ulcer), children will also receive prophylactic Prilosec (omeprazole) for the duration of the study, during both the mycophenolate and placebo arms.
Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a fatal disorder. Currently treatment is symptomatic. Thus, there is a real need to intervene and slow the progression of this disease. Preliminary data on genetic knock-down of the ability to mount an immune response in cln3-knockout mice is supportive of a strategy for treating JNCL with an immuno-suppressive agent. Many drugs with the ability to suppress the immune system are steroidal and deemed unsuitable for long-term administration to children. Mycophenolate mofetil (CellCept) is used as an immunosuppressive agent in allogenic transplants in pediatric patients and is therefore approved by the Food and Drug Administration (FDA) for pediatric use.
The study design is a double-blind, randomized, 22-week cross-over study of mycophenolate mofetil vs. placebo. After a 4-week washout period, subjects will undergo blinded crossover from active study drug to placebo or from placebo to active study drug.
Subjects and caregivers will be evaluated in person in the University of Rochester Batten Center (URBC) at screening/baseline, and at weeks 8, 12, and 20. In addition, subjects will be evaluated by their local clinician who is a formalized member of the research team. Such contacts will occur at Weeks 2, 4, 14, 16, and any unscheduled or early termination visits. There will also be regular telephone contact between the URBC and the local clinician.
We have selected the dosage currently FDA approved for use in children being treated for prophylaxis of renal transplant rejection.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01399047
|United States, New York|
|University of Rochester|
|Rochester, New York, United States, 14642|
|Principal Investigator:||Erika F Augustine, MD||University of Rochester|