Pantothenate Kinase-Associated NeurodegenerationPhase 3NCT01741532
Efficacy and Safety Study of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN)
A Phase 3 study testing Deferiprone oral solution in people with Pantothenate Kinase-Associated Neurodegeneration, run by ApoPharma at 4 sites in 4 countries.
Trial summary
A multi-center, placebo controlled, double-blind trial comparing the efficacy and safety of 18 months of treatment with deferiprone versus placebo in patients with PKAN. This investigator-initiated trial was funded by the European Commission's Seventh Framework Programme (FP7/2007-2013, HEALTH-F2-2011, grant agreement… Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Pantothenate Kinase-Associated Neurodegeneration
- What is being tested?
- Deferiprone oral solution
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 89 participants
- Where
- 4 sitesin 4 countries
- Study dates
- 13 Dec 2012to 11 Jan 2017
- Phase
- Phase 3
- 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 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Main Inclusion Criteria:
- Males or females 4 years of age and older at screening visit;
- Have PKAN, confirmed by genetic testing (supporting evidence required);
- Barry-Albright Dystonia (BAD) total score ≥ 3 at the screening visit;
- Patients who have Deep Brain Stimulation (DBS) systems or baclofen pumps in place will be eligible for the study, but they must have had a stable setting for at least two months prior to the screening visit and stimulation parameters / pump settings must remain stable for the duration of the trial:
Main Exclusion Criteria:
- Evidence of iron deficiency defined by Fe:TIBC ratio <15%, or serum ferritin <12 ng/mL;
- Treatment with deferiprone in the past 12 months;
- Previous failure of treatment with deferiprone, or previous discontinuation of treatment with deferiprone due to adverse events;
- Conditions known to contraindicate the use of deferiprone (history of agranulocytosis or recurrent episodes of neutropenia);
- A serious, unstable chronic illness not related to PKAN condition during the past 3 months before screening visit including but not limited to: hepatic, renal, gastro-enterologic, respiratory, cardiovascular, endocrinologic, neurologic or immunologic disease;
- Evidence of abnormal liver or renal function (serum liver enzyme level(s) > 3 times upper limit of normal at screening) or abnormal creatinine levels at screening visit;
- Disorders associated with neutropenia (ANC < 1.5 x 10^9/L) or thrombocytopenia (platelet count < 50 x 10^9/L) in the 12 months preceding the initiation of the study medication. Exception: for patients whose neutropenia was attributed by the treating physician to episodes of infection or to drugs associated with a decline in the neutrophil count and in whom the ANC has fully recovered at the screening visit;
- History of malignancy;
Other protocol inclusion or exclusion criteria may apply.
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
United States1 site
Children's Hospital & Research Center at Oakland
Oakland, California, 94609
United Kingdom1 site
Newcastle University Institute of Human Genetics
Newcastle upon Tyne, NE1 3BZ
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Trial of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN)
A multi-center, placebo controlled, double-blind trial comparing the efficacy and safety of 18 months of treatment with deferiprone versus placebo in patients with PKAN.
This investigator-initiated trial was funded by the European Commission's Seventh Framework Programme (FP7/2007-2013, HEALTH-F2-2011, grant agreement No. 277984) to the TIRCON consortium (Treat Iron-Related Childhood-Onset Neurodegeneration) and by the FDA Office of Orphan Products Development (OOPD) (Dr. Elliott Vichinsky).
Read the detailed description
This is a multi-center, double-blind, randomized, placebo-controlled, 18-month study in patients with PKAN aged 4 years and older. Participants are randomized in a 2:1 ratio to receive either deferiprone oral solution or placebo, twice a day for 18 months. Efficacy assessments, an MRI scan to measure iron levels in the globus pallidus, pharmacokinetic evaluations, and safety assessments are conducted at specified time points. Following completion of the trial, eligible patients are invited to enroll in an 18-month extension study, TIRCON2012V1-EXT, in which all participants receive deferiprone.
- Being tested
- Deferiprone oral solution, Placebo
- Keywords
- Pantothenate Kinase-associated Neurodegeneration, PKAN, NBIA, Deferiprone, Ferriprox, Neurodegeneration with brain iron accumulation
- Medical subject headings
- Pantothenate Kinase-Associated Neurodegeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deferiprone oral solutionDrug
Also called DFP, L1
Deferiprone 80 mg/mL oral solution will be administered twice daily (b.i.d.) for 18 months. An initial dose of 5 mg/kg b.i.d. will be administered for 6 weeks. The dose will then be escalated to 10 mg/kg b.i.d. and finally to 15 mg/kg b.i.d.
PlaceboDrug
A deferiprone matching placebo oral solution will be given twice daily for 18 months.
| Study group | Role | What they receive |
|---|---|---|
| Deferiprone | Experimental | Deferiprone 80 mg/mL oral solution Receives: Drug: Deferiprone oral solution |
| Placebo | Placebo comparator | Matching placebo solution Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Score on Barry-Albright Dystonia Scale
The Barry-Albright Dystonia (BAD) scale rates severity of dystonia (sustained muscle contractions causing twisting and repetitive movements or abnormal postures) in 8 body regions. The individual scores are summed to provide a total score ranging from 0 to 32, with higher scores indicating greater severity. The co-primary endpoint in this study was the change from baseline to Month 18 in BAD total score.
Measured: Baseline to 18 Months
Score on Patient Global Impression of Improvement at End of Study
The Patient Global Impression of Improvement (PGI-I) is a global index that assesses the response of a condition to a therapy by asking patients to rate their current state relative to their state at baseline. It consists of a 7-point rating scale, where 1=very much improved, 2= much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
Measured: Month 18
Secondary outcomes (6)
Change in Score on Unified Parkinson's Disease Rating Scale
The Unified Parkinson's Disease Rating Scale (UPDRS) is the major rating scale used to assess severity of symptoms of Parkinson's disease, some of which are similar to those of PKAN. The UPDRS subscales used in this study were Part I: Mentation, Behavior and Mood, scored from 0 (best) to 16 (worst); Part II: Activities of Daily Living, scored from 0 (best) to 52 (worst); Part III: Motor Examination, scored from 0 (best) to 108 (worst); and Part VI: Schwab and England Activities of Daily Living Scale, scored from 0% (worst) to 100% (best).
Measured: Baseline to 18 Months
Change in Score on Functional Independence Measure
The Functional Independence Measure (FIM) scale is used to assess physical and cognitive disability in three areas of daily living: self-care, mobility, and cognition. Within each area, items are scored according to the level of assistance required to perform that activity of daily living. A score of 1-2 indicates that the patient is completely dependent on a helper to perform the task, a score of 3-5 indicates that the patient is moderately dependent, and a score of 6-7 indicates that no help is required. The individual scores are summed to provide a global score from 18 (worst) to 126 (best).
Measured: Baseline to 18 Months
Change in Score on WeeFIM
The WeeFIM is the pediatric version of the Functional Independence Measure scale, and is used to assess physical and cognitive disability in three areas of daily living: self-care, mobility, and cognition. Within each area, items are scored according to the level of assistance required to perform that activity of daily living. A score of 1-2 indicates that the patient is completely dependent on a helper to perform the task, a score of 3-5 indicates that the patient is moderately dependent, and a score of 6-7 indicates that no help is required. The individual scores are summed to provide a global score from 18 (worst) to 126 (best).
Measured: Baseline to 18 Months
Change in Score on Pediatric Quality of Life
The Pediatric Quality of Life (PedsQL) questionnaire is used to measure functional health and well-being from the patient's point of view. Separate versions of the questionnaire are available for children, young adults aged 18-25 years, and adults older than 25 years. Patients are asked to indicate how they have felt over the past month, and the scores of the 23 questions are used to generate an overall score that ranges from 0 (worst) to 100 (best).
Measured: Baseline to 18 Months
Change in Score on Pittsburgh Sleep Quality Index
The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire that assesses sleep quality and disturbances over a 1-month time interval. A total of 19 individual items are used to generate 7 "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction, and a score is generated that ranges from 0 (best) to 21 (worst).
Measured: Baseline to 18 Months
Change in Level of Brain Iron
Neurodegeneration in patients with PKAN is associated with localized brain iron accumulation, with the highest amount of accumulation seen in the globus pallidus, one of the main areas for motor control. MRI R2* scans of this region were performed at baseline and Month 18 in a subset of patients who did not have a deep brain stimulation (DBS) device implanted, and for whom the use of anesthesia, if required, was deemed acceptable by the investigator.
Measured: Baseline to 18 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2012 (estimated)
- Study start13 Dec 2012
- Primary completion21 Oct 2016
- Study completion11 Jan 2017
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 (1)Papers the sponsor has linked to this study.
- Other trials for Pantothenate Kinase-Associated NeurodegenerationStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 89 participants (actual)
Sponsor and investigators
- Lead sponsor
- ApoPharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Food and Drug Administration (FDA)
- Responsible party
- Sponsor
- Investigators
- Fernando Tricta, MD, Study chair, ApoPharma Inc.Thomas Klopstock, MD, Principal investigator, Friedrich-Baur-Institute, Department of Neurology, University of Munich ZiemssenstrElliott Vichinsky, MD, Principal investigator, Children's Hospital & Research Center at Oakland Hematology/ Oncology, Pediatric Rehabilitation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01741532
- Sponsor's protocol ID
- TIRCON2012V1
- Other IDs
- 1R01FD004103-01
- Status last verified
- Jun 2019
- First submitted
- 3 Dec 2012
- Last updated
- 5 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Klopstock T, Tricta F, Neumayr L, Karin I, Zorzi G, Fradette C, Kmiec T, Buchner B, Steele HE, Horvath R, Chinnery PF, Basu A, Kupper C, Neuhofer C, Kalman B, Dusek P, Yapici Z, Wilson I, Zhao F, Zibordi F, Nardocci N, Aguilar C, Hayflick SJ, Spino M, Blamire AM, Hogarth P, Vichinsky E. Safety and efficacy of deferiprone for pantothenate kinase-associated neurodegeneration: a randomised, double-blind, controlled trial and an open-label extension study. Lancet Neurol. 2019 Jul;18(7):631-642. doi: 10.1016/S1474-4422(19)30142-5.
PubMed 31202468
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Trial of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN)
- ClinicalTrials.gov ID
- NCT01741532
- Acronym / sponsor ID
- TIRCON2012V1
- Keywords
- Pantothenate Kinase-associated Neurodegeneration, PKAN, NBIA, Deferiprone, Ferriprox, Neurodegeneration with brain iron accumulation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 89 participants (actual)
- Lead sponsor
- ApoPharmaIndustry (pharma, biotech, devices)
- Collaborators
- Food and Drug Administration (FDA)
- Study start
- 13 Dec 2012 (actual)
- Primary completion
- 21 Oct 2016 (actual)
- Study completion
- 11 Jan 2017 (actual)
- First posted
- 5 Dec 2012 (estimated)
- Results
- Posted 23 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A multi-center, placebo controlled, double-blind trial comparing the efficacy and safety of 18 months of treatment with deferiprone versus placebo in patients with PKAN.
This investigator-initiated trial was funded by the European Commission's Seventh Framework Programme (FP7/2007-2013, HEALTH-F2-2011, grant agreement No. 277984) to the TIRCON consortium (Treat Iron-Related Childhood-Onset Neurodegeneration) and by the FDA Office of Orphan Products Development (OOPD) (Dr. Elliott Vichinsky).
Detailed description
This is a multi-center, double-blind, randomized, placebo-controlled, 18-month study in patients with PKAN aged 4 years and older. Participants are randomized in a 2:1 ratio to receive either deferiprone oral solution or placebo, twice a day for 18 months. Efficacy assessments, an MRI scan to measure iron levels in the globus pallidus, pharmacokinetic evaluations, and safety assessments are conducted at specified time points. Following completion of the trial, eligible patients are invited to enroll in an 18-month extension study, TIRCON2012V1-EXT, in which all participants receive deferiprone.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Deferiprone | Experimental | Drug: Deferiprone oral solutionDeferiprone 80 mg/mL oral solution |
| Placebo | Placebo comparator | Drug: PlaceboMatching placebo solution |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
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 |
|---|---|---|
| Deferiprone oral solutionAlso: DFP, L1Deferiprone 80 mg/mL oral solution will be administered twice daily (b.i.d.) for 18 months. An initial dose of 5 mg/kg b.i.d. will be administered for 6 weeks. The dose will then be escalated to 10 mg/kg b.i.d. and finally to 15 mg/kg b.i.d. | Drug | Deferiprone |
| PlaceboA deferiprone matching placebo oral solution will be given twice daily for 18 months. | Drug | Placebo |
Primary outcome
Change in Score on Barry-Albright Dystonia Scale
Time frame: Baseline to 18 Months
The Barry-Albright Dystonia (BAD) scale rates severity of dystonia (sustained muscle contractions causing twisting and repetitive movements or abnormal postures) in 8 body regions. The individual scores are summed to provide a total score ranging from 0 to 32, with higher scores indicating greater severity. The co-primary endpoint in this study was the change from baseline to Month 18 in BAD total score.
Score on Patient Global Impression of Improvement at End of Study
Time frame: Month 18
The Patient Global Impression of Improvement (PGI-I) is a global index that assesses the response of a condition to a therapy by asking patients to rate their current state relative to their state at baseline. It consists of a 7-point rating scale, where 1=very much improved, 2= much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
6 secondary outcomes
Change in Score on Unified Parkinson's Disease Rating Scale
Time frame: Baseline to 18 Months
Change in Score on Functional Independence Measure
Time frame: Baseline to 18 Months
Change in Score on WeeFIM
Time frame: Baseline to 18 Months
Change in Score on Pediatric Quality of Life
Time frame: Baseline to 18 Months
Change in Score on Pittsburgh Sleep Quality Index
Time frame: Baseline to 18 Months
Change in Level of Brain Iron
Time frame: Baseline to 18 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31202468Klopstock T, Tricta F, Neumayr L, Karin I, Zorzi G, Fradette C, Kmiec T, Buchner B, Steele HE, Horvath R, Chinnery PF, Basu A, Kupper C, Neuhofer C, Kalman B, Dusek P, Yapici Z, Wilson I, Zhao F, Zibordi F, Nardocci N, Aguilar C, Hayflick SJ, Spino M, Blamire AM, Hogarth P, Vichinsky E. Safety and efficacy of deferiprone for pantothenate kinase-associated neurodegeneration: a randomised, double-blind, controlled trial and an open-label extension study. Lancet Neurol. 2019 Jul;18(7):631-642. doi: 10.1016/S1474-4422(19)30142-5.
Related trials for Pantothenate Kinase-Associated Neurodegeneration
Not yet recruiting
Brain Iron in Beta-Propeller Protein Associated Neurodegeneration (BPAN)
Neurodegeneration With Brain Iron Accumulation (NBIA), Iron Metabolism Disorders
RecruitingObservational study
Neurodegenerative Diseases Progression Markers (MARKERS-NDD)
Neurodegenerative Diseases, Parkinson Disease
RecruitingObservational study
TIRCON International NBIA Registry
Neurodegeneration With Brain Iron Accumulation (NBIA), Pantothenate Kinase-associated Neurodegeneration (PKAN)
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.
Fernando Tricta, MD study chair
ApoPharma Inc.
Thomas Klopstock, MD principal investigator
Friedrich-Baur-Institute, Department of Neurology, University of Munich Ziemssenstr
Elliott Vichinsky, MD principal investigator
Children's Hospital & Research Center at Oakland Hematology/ Oncology, Pediatric Rehabilitation
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Deferiprone oral solution in people with Pantothenate Kinase-Associated Neurodegeneration, run by ApoPharma at 4 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 5 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Germany, Italy, United Kingdom. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 May 2019). 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?
Change in Score on Barry-Albright Dystonia Scale (time frame: Baseline to 18 Months). The study lists 2 primary outcomes in all. 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 NCT01741532, which also lists 1 linked publication.
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 5 Jul 2019.