Juvenile Neuronal Ceroid LipofuscinosisPhase 2JUMPNCT01399047
Cellcept for Treatment of Juvenile Neuronal Ceroid Lipofuscinosis
A Phase 2 study testing Mycophenolate mofetil in people with Juvenile Neuronal Ceroid Lipofuscinosis, run by University of Rochester at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 6 to 25 years
- Conditions the study is for
- Juvenile Neuronal Ceroid Lipofuscinosis
- What is being tested?
- Mycophenolate mofetil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2011to Nov 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II, Randomized, Placebo Controlled Trial of the Safety and Tolerability of Mycophenolate in Children With Juvenile Neuronal Ceroid Lipofuscinosis
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).
Read the 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.
- Conditions
- Juvenile Neuronal Ceroid Lipofuscinosis
- Being tested
- Mycophenolate mofetil, Liquid Placebo
- Keywords
- Batten Disease
- Medical subject headings
- Neuronal Ceroid-Lipofuscinoses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Cellcept
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.
Liquid PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Mycophenolate Mofetil | Active comparator | Not described Receives: Drug: Mycophenolate mofetil |
| Placebo liquid | Placebo comparator | Not described Receives: Drug: Liquid Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to 8 weeks
Secondary outcomes (4)
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.
Measured: Baseline to 8 weeks
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.
Measured: Baseline to 8 weeks
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.
Measured: Baseline to 8 weeks
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.
Measured: Baseline to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2011 (estimated)
- Study startJul 2011
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Juvenile Neuronal Ceroid LipofuscinosisStudies of the same condition, open and under way.
- More trials run by University of RochesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Collaborators
- Batten Disease Support and Research Assocation (BDSRA)
- Responsible party
- Principal investigator, Erika Augustine, University of Rochester
- Investigators
- Erika F Augustine, MD, Principal investigator, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01399047
- Sponsor's protocol ID
- 3908
- Acronym
- JUMP
- Status last verified
- May 2019
- First submitted
- 5 Jul 2011
- Last updated
- 21 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 31184505Augustine 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.
PubMed 24014509
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II, Randomized, Placebo Controlled Trial of the Safety and Tolerability of Mycophenolate in Children With Juvenile Neuronal Ceroid Lipofuscinosis
- ClinicalTrials.gov ID
- NCT01399047
- Acronym / sponsor ID
- JUMP / 3908
- Conditions
- Juvenile Neuronal Ceroid Lipofuscinosis
- Keywords
- Batten Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Collaborators
- Batten Disease Support and Research Assocation (BDSRA)
- Study start
- Jul 2011
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 21 Jul 2011 (estimated)
- Results
- Posted 23 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mycophenolate Mofetil | Active comparator | Drug: Mycophenolate mofetil |
| Placebo liquid | Placebo comparator | Drug: Liquid Placebo |
Who may qualify
- Ages
- 6 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mycophenolate mofetilAlso: CellceptThe 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. | Drug | Mycophenolate Mofetil |
| Liquid PlaceboThe 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. | Drug | Placebo liquid |
Primary outcome
Tolerability - Number of Participants Who Completed Each Arm on Assigned Study Drug Dose
Time frame: Baseline to 8 weeks
The primary outcome measure is tolerability, defined as the completion of 8 weeks on the assigned dosage of study drug.
4 secondary outcomes
Unified Batten Disease Rating Scale Physical Subscale Change
Time frame: Baseline to 8 weeks
Unified Batten Disease Rating Scale Seizure Subscale Change
Time frame: Baseline to 8 weeks
Unified Batten Disease Rating Scale Behavior Subscale Change
Time frame: Baseline to 8 weeks
Unified Batten Disease Rating Scale Capability Subscale Change
Time frame: Baseline to 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31184505Adams 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.
- Derived from this study: PubMed 24014509Augustine 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erika F Augustine, MD principal investigator
University of Rochester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mycophenolate mofetil in people with Juvenile Neuronal Ceroid Lipofuscinosis, run by University of Rochester at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tolerability - Number of Participants Who Completed Each Arm on Assigned Study Drug Dose (time frame: Baseline to 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01399047, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2019.