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Cellcept for Treatment of Juvenile Neuronal Ceroid Lipofuscinosis (JUMP)

Primary Purpose

Juvenile Neuronal Ceroid Lipofuscinosis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Mycophenolate mofetil
Liquid Placebo
Sponsored by
University of Rochester
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Juvenile Neuronal Ceroid Lipofuscinosis focused on measuring Batten Disease

Eligibility Criteria

6 Years - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • JNCL as determined by a characteristic clinical presentation and confirmatory genetic evidence.
  • Able to walk 10 feet without assistance beyond that required due to vision impairment.
  • Subjects with local treating clinician (pediatrician or neurologist) willing to conduct the trial according to the protocol, good clinical practice, and applicable regulations.
  • Subjects with a parent/legal guardian willing to accompany them to all study visits, oversee study drug compliance, and monitor and report to local treating clinician/investigator and the URBC investigative personnel any signs of adversity.

Exclusion Criteria:

  • Inability to tolerate oral administration of medications
  • Concomitant medical condition, which, in the opinion of the local treating clinician, the parent(s)/guardian, or the URBC study investigator would place the child at greater than acceptable risk from: 1) travel by plane or car to the URBC on four occasions over the course of 22 weeks, 2) exposure to mycophenolate mofetil at protocol defined dosages for periods up to 8 weeks.
  • Anticipated inability of the child (on the part of the investigator, parent/guardian, or URBC study personnel) to comply with the rigors of the protocol..
  • Use of disallowed concomitant medications.
  • Administration of immunosuppressive medications
  • History of any prior exposure to mycophenolate mofetil
  • History of hypersensitivity to mycophenolate mofetil, or any other component of the product
  • History of frank gastrointestinal hemorrhage, ulceration, or melena
  • White blood cell count < 3000/μL, absolute neutrophil count (ANC) < 1500/μL, hemoglobin < 10g/dL, or thrombocytopenia <100,000/μL.
  • Abnormal liver function (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or bilirubin greater than 3 times the upper limit of normal)
  • Pregnancy or vulnerability to engage in sexual intercourse based on report of the parent/guardian, judgment of the local treating clinician/investigator or judgment of the URBC study personnel.
  • Positive Tuberculosis test
  • Immunizations not up to date for age according to Centers for Disease Control guidelines

Sites / Locations

  • University of Rochester

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Mycophenolate Mofetil

Placebo liquid

Arm Description

Outcomes

Primary Outcome Measures

Tolerability - Number of Participants Who Completed Each Arm on Assigned Study Drug Dose
The primary outcome measure is tolerability, defined as the completion of 8 weeks on the assigned dosage of study drug.

Secondary Outcome Measures

Unified Batten Disease Rating Scale Physical Subscale Change
The Unified Batten Disease Rating Scale (UBDRS) is a disease-specific clinical assessment. Motor impairment was measured by the physical subscale of the UBDRS with a range of 0-112 with zero indicating better outcome. The overall treatment effect was determined - mean difference in physical subscale change (Mycophenolate minus placebo periods) in outcome, adjusted for baseline value and period effects.
Unified Batten Disease Rating Scale Seizure Subscale Change
The Unified Batten Disease Rating Scale (UBDRS) is a disease-specific clinical assessment. Seizure severity was measured by the seizure subscale of the UBDRS with a range of 0-54 with zero indicating better outcome. The overall treatment effect was determined - mean difference in seizure subscale change (Mycophenolate minus placebo periods) in outcome, adjusted for baseline value and period effects.
Unified Batten Disease Rating Scale Behavior Subscale Change
The Unified Batten Disease Rating Scale (UBDRS) is a disease-specific clinical assessment. Mood and behavior severity was measured by the behavior subscale of the UBDRS with a range of 0-55 with zero indicating better outcome. The overall treatment effect was determined - mean difference in behavior subscale change (Mycophenolate minus placebo periods) in outcome, adjusted for baseline value and period effects.
Unified Batten Disease Rating Scale Capability Subscale Change
The Unified Batten Disease Rating Scale (UBDRS) is a disease-specific clinical assessment. Capability severity was measured by the capability subscale of the UBDRS with a range of 0-14 with higher scores indicating better outcome. The overall treatment effect was determined - mean difference in capability subscale change (Mycophenolate minus placebo periods) in outcome, adjusted for baseline value and period effects.

Full Information

First Posted
July 5, 2011
Last Updated
May 7, 2019
Sponsor
University of Rochester
Collaborators
Batten Disease Support and Research Assocation (BDSRA)
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1. Study Identification

Unique Protocol Identification Number
NCT01399047
Brief Title
Cellcept for Treatment of Juvenile Neuronal Ceroid Lipofuscinosis
Acronym
JUMP
Official Title
Phase II, Randomized, Placebo Controlled Trial of the Safety and Tolerability of Mycophenolate in Children With Juvenile Neuronal Ceroid Lipofuscinosis
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Rochester
Collaborators
Batten Disease Support and Research Assocation (BDSRA)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Juvenile Neuronal Ceroid Lipofuscinosis
Keywords
Batten Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Mycophenolate Mofetil
Arm Type
Active Comparator
Arm Title
Placebo liquid
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Mycophenolate mofetil
Other Intervention Name(s)
Cellcept
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Liquid Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Tolerability - Number of Participants Who Completed Each Arm on Assigned Study Drug Dose
Description
The primary outcome measure is tolerability, defined as the completion of 8 weeks on the assigned dosage of study drug.
Time Frame
Baseline to 8 weeks
Secondary Outcome Measure Information:
Title
Unified Batten Disease Rating Scale Physical Subscale Change
Description
The Unified Batten Disease Rating Scale (UBDRS) is a disease-specific clinical assessment. Motor impairment was measured by the physical subscale of the UBDRS with a range of 0-112 with zero indicating better outcome. The overall treatment effect was determined - mean difference in physical subscale change (Mycophenolate minus placebo periods) in outcome, adjusted for baseline value and period effects.
Time Frame
Baseline to 8 weeks
Title
Unified Batten Disease Rating Scale Seizure Subscale Change
Description
The Unified Batten Disease Rating Scale (UBDRS) is a disease-specific clinical assessment. Seizure severity was measured by the seizure subscale of the UBDRS with a range of 0-54 with zero indicating better outcome. The overall treatment effect was determined - mean difference in seizure subscale change (Mycophenolate minus placebo periods) in outcome, adjusted for baseline value and period effects.
Time Frame
Baseline to 8 weeks
Title
Unified Batten Disease Rating Scale Behavior Subscale Change
Description
The Unified Batten Disease Rating Scale (UBDRS) is a disease-specific clinical assessment. Mood and behavior severity was measured by the behavior subscale of the UBDRS with a range of 0-55 with zero indicating better outcome. The overall treatment effect was determined - mean difference in behavior subscale change (Mycophenolate minus placebo periods) in outcome, adjusted for baseline value and period effects.
Time Frame
Baseline to 8 weeks
Title
Unified Batten Disease Rating Scale Capability Subscale Change
Description
The Unified Batten Disease Rating Scale (UBDRS) is a disease-specific clinical assessment. Capability severity was measured by the capability subscale of the UBDRS with a range of 0-14 with higher scores indicating better outcome. The overall treatment effect was determined - mean difference in capability subscale change (Mycophenolate minus placebo periods) in outcome, adjusted for baseline value and period effects.
Time Frame
Baseline to 8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: JNCL as determined by a characteristic clinical presentation and confirmatory genetic evidence. Able to walk 10 feet without assistance beyond that required due to vision impairment. Subjects with local treating clinician (pediatrician or neurologist) willing to conduct the trial according to the protocol, good clinical practice, and applicable regulations. Subjects with a parent/legal guardian willing to accompany them to all study visits, oversee study drug compliance, and monitor and report to local treating clinician/investigator and the URBC investigative personnel any signs of adversity. Exclusion Criteria: Inability to tolerate oral administration of medications Concomitant medical condition, which, in the opinion of the local treating clinician, the parent(s)/guardian, or the URBC study investigator would place the child at greater than acceptable risk from: 1) travel by plane or car to the URBC on four occasions over the course of 22 weeks, 2) exposure to mycophenolate mofetil at protocol defined dosages for periods up to 8 weeks. Anticipated inability of the child (on the part of the investigator, parent/guardian, or URBC study personnel) to comply with the rigors of the protocol.. Use of disallowed concomitant medications. Administration of immunosuppressive medications History of any prior exposure to mycophenolate mofetil History of hypersensitivity to mycophenolate mofetil, or any other component of the product History of frank gastrointestinal hemorrhage, ulceration, or melena White blood cell count < 3000/μL, absolute neutrophil count (ANC) < 1500/μL, hemoglobin < 10g/dL, or thrombocytopenia <100,000/μL. Abnormal liver function (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or bilirubin greater than 3 times the upper limit of normal) Pregnancy or vulnerability to engage in sexual intercourse based on report of the parent/guardian, judgment of the local treating clinician/investigator or judgment of the URBC study personnel. Positive Tuberculosis test Immunizations not up to date for age according to Centers for Disease Control guidelines
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Erika F Augustine, MD
Organizational Affiliation
University of Rochester
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
31184505
Citation
Adams HR, Defendorf S, Vierhile A, Mink JW, Marshall FJ, Augustine EF. A novel, hybrid, single- and multi-site clinical trial design for CLN3 disease, an ultra-rare lysosomal storage disorder. Clin Trials. 2019 Oct;16(5):555-560. doi: 10.1177/1740774519855715. Epub 2019 Jun 11.
Results Reference
derived
PubMed Identifier
24014509
Citation
Augustine EF, Adams HR, Mink JW. Clinical trials in rare disease: challenges and opportunities. J Child Neurol. 2013 Sep;28(9):1142-50. doi: 10.1177/0883073813495959.
Results Reference
derived

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Cellcept for Treatment of Juvenile Neuronal Ceroid Lipofuscinosis

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