A Phase 3 interventional study of Deferiprone oral solution and Placebo in Pantothenate Kinase-Associated Neurodegeneration, sponsored by ApoPharma. Completed at 4 sites in 4 countries. Open to participants aged 4 Years and older. Per ClinicalTrials.gov, last updated 2019-07-05.
Sponsored by ApoPharma (part of Chiesi Farmaceutici S.p.A.) · Phase 3, Interventional, and Treatment
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).
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.
ApoPharma is the lead sponsor of 23 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Main Inclusion Criteria:
Main Exclusion Criteria:
Other protocol inclusion or exclusion criteria may apply.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Deferiprone 80 mg/mL oral solution
Drug: Deferiprone oral solution
Matching placebo solution
Drug: Placebo
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.
Also known as: DFP, L1
A deferiprone matching placebo oral solution will be given twice daily for 18 months.
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.
Time frame: 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.
Time frame: Month 18
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).
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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.
Time frame: Baseline to 18 Months
Patients were recruited at 4 study sites in Germany, Italy, the U.K., and the U.S.
| Milestone | Deferiprone | Placebo |
|---|---|---|
| Started | 59 | 30 |
| Exposed | 58 | 30 |
| Provided post-baseline efficacy data | 58 | 28 |
| Completed | 49 | 27 |
| Not completed | 10 | 3 |
| Withdrew: Adverse event | 4 | 0 |
| Withdrew: Withdrawal by subject | 1 | 1 |
| Withdrew: Protocol violation | 0 | 1 |
| Withdrew: Worsening of the disease | 3 | 1 |
| Withdrew: Sponsor decision | 1 | 0 |
| Withdrew: Medical event | 1 | 0 |
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 a scale | Deferiprone | Placebo |
|---|---|---|
| Change in Score on Barry-Albright Dystonia Scale | 2.48 ± 0.63 | 3.99 ± 0.82 |
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.
| score on a scale | Deferiprone | Placebo |
|---|---|---|
| Score on Patient Global Impression of Improvement at End of Study | 4.55 ± 0.30 | 4.66 ± 0.38 |
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).
| score on a scale | Deferiprone | Placebo |
|---|---|---|
| UPDRS Part I | -0.25 ± 0.43 | -0.07 ± 0.55 |
| UPDRS Part II | 1.09 ± 1.19 | 2.36 ± 1.52 |
| UPDRS Part III | 5.38 ± 2.20 | 2.06 ± 2.79 |
| UPDRS Part VI | -2.17 ± 2.94 | -7.66 ± 3.85 |
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).
| score on a scale | Deferiprone | Placebo |
|---|---|---|
| Change in Score on Functional Independence Measure | 5.40 ± 2.36 | 0.69 ± 3.34 |
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).
| score on a scale | Deferiprone | Placebo |
|---|---|---|
| Change in Score on WeeFIM | 4.91 ± 5.30 | -2.40 ± 5.42 |
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).
| score on a scale | Deferiprone | Placebo |
|---|---|---|
| Patient self-report, total score | 1.21 ± 3.68 | 1.34 ± 4.49 |
| Parent proxy-report, total score | -4.90 ± 3.99 | -2.37 ± 4.90 |
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).
| score on a scale | Deferiprone | Placebo |
|---|---|---|
| Change in Score on Pittsburgh Sleep Quality Index | 0.48 ± 0.61 | 0.14 ± 0.80 |
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.
| Hz | Deferiprone | Placebo |
|---|---|---|
| Change in Level of Brain Iron | -36.1 ± 3.11 | -0.50 ± 3.97 |
Collected over Adverse events were collected from baseline until 30 days after the last dose of study medication.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Deferiprone | 0/58 (0%) | 18/58 (31%) | 57/58 (98.3%) |
| Placebo | 0/30 (0%) | 10/30 (33.3%) | 30/30 (100%) |
| Event | Deferiprone | Placebo |
|---|---|---|
| NeutropeniaBlood and lymphatic system disorders | 5/58 | 2/30 |
| DystoniaNervous system disorders | 3/58 | 2/30 |
| BronchitisInfections and infestations | 2/58 | 0/30 |
| PneumoniaInfections and infestations | 2/58 | 0/30 |
| Medical device battery replacementSurgical and medical procedures | 2/58 | 1/30 |
| NauseaGastrointestinal disorders | 0/58 | 1/30 |
| VomitingGastrointestinal disorders | 1/58 | 1/30 |
| Condition aggravatedGeneral disorders | 0/58 | 1/30 |
| Cytomegalovirus infectionInfections and infestations | 0/58 | 1/30 |
| Pneumonia bacterialInfections and infestations | 0/58 | 1/30 |
| Event | Deferiprone | Placebo |
|---|---|---|
| DystoniaNervous system disorders | 25/58 | 14/30 |
| PyrexiaGeneral disorders | 16/58 | 13/30 |
| Serum ferritin decreasedInvestigations | 19/58 | 5/30 |
| Condition aggravatedGeneral disorders | 10/58 | 9/30 |
| HeadacheNervous system disorders | 13/58 | 9/30 |
| VomitingGastrointestinal disorders | 9/58 | 8/30 |
| AnaemiaBlood and lymphatic system disorders | 12/58 | 0/30 |
| NasopharyngitisInfections and infestations | 11/58 | 6/30 |
| Neutrophil count decreasedInvestigations | 10/58 | 3/30 |
| Pain in extremityMusculoskeletal and connective tissue disorders | 10/58 | 4/30 |
| Age, Continuous(years) | Deferiprone | Placebo | Total |
|---|---|---|---|
| Mean | 20.8 ± 10.7 | 19.2 ± 12.5 | 20.2 ± 11.3 |
| Sex: Female, Male(Participants) | Deferiprone | Placebo | Total |
|---|---|---|---|
| Female | 25 | 17 | 42 |
| Male | 34 | 13 | 47 |
| Race (NIH/OMB)(Participants) | Deferiprone | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 6 | 1 | 7 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 2 | 0 | 2 |
| White | 51 | 28 | 79 |
| More than one race | 0 | 1 | 1 |
| Unknown or Not Reported | 0 | 0 | 0 |
This study is completed, as verified in Jun 2019. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Deferiprone
Pantothenate Kinase-Associated Neurodegeneration