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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-000845-11 | EudraCT Number |
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Patients with PKAN will be treated with the iron chelator deferiprone for 18 months. Only patients who have completed the earlier study TIRCON2012V1 (NCT01741532), a double-blind placebo-controlled trial in which participants were randomized to receive either deferiprone or placebo for 18 months, are eligible to enroll.
TIRCON2012V1-EXT is a multi-center, single-arm, open-label study. All patients who completed the earlier study TIRCON2012V1 (NCT01741532) are eligible to take part. In the initial study, patients were randomized in a 2:1 ratio to receive 18 months of treatment with either the iron chelator deferiprone or placebo, respectively. In this extension study, all participants will receive deferiprone for 18 months. Thus, depending on which product was received earlier, patients will be on deferiprone for a total of either 1.5 years or 3 years. As in the earlier study, assessments will be carried out every six months to look at the safety of the drug and to see if patients are showing any improvement in dystonia and other symptoms of PKAN.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Deferiprone | Experimental | All patients will receive deferiprone oral solution. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Deferiprone oral solution | Drug | Deferiprone oral solution at a dosage of up to 15 mg per kilogram of body weight, twice a day |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events | Safety and tolerability were assessed based on changes in: frequency of adverse events (AEs), frequency of serious adverse events (SAEs), and discontinuation due to AEs. No statistical comparison between the groups was conducted as all participants received the same study product. | 18 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Score on the BAD Scale -- Comparison of Treatment Groups Over Each Study | The Barry-Albright Dystonia (BAD) scale is an instrument for rating the severity of dystonia in eight body regions. The individual scores are summed to provide a total score that ranges from 0 to 32; the higher the score, the more severe the dystonia. Patients were assessed for the change in total BAD score over the course of both the initial study (during which one group received placebo and the other received deferiprone) and the extension study (during which both groups received deferiprone). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Elliott Vichinsky, MD | UCSF Benioff Children's Hospital Oakland | Principal Investigator |
| Thomas Klopstock, MD | Klinikum der Universität München | Principal Investigator |
| Nardo Nardocci, MD | Foundation Neurological Institute C. Besta | Principal Investigator |
| Patrick Chinnery, MD | Newcastle University Institute of Human Genetics | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Benioff Children's Hospital Oakland | Oakland | California | 94609 | United States | ||
| Klinikum der Universität München |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo-DFP | Patients in this group had been randomized to placebo treatment in the TIRCON2012V1 study and were then switched to deferiprone in the extension study. Accordingly, they received up to 18 months of deferiprone treatment over the duration of the two studies. |
| FG001 | DFP-DFP | Patients in this group had been randomized to deferiprone treatment in the TIRCON2012V1 study and then continued on deferiprone in the extension study. Accordingly, they received up to 36 months of deferiprone treatment over the duration of the two studies. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo-DFP | Patients who received 18 months of placebo treatment in the TIRCON2012V1 study and were then switched to deferiprone in the extension study, so received up to 18 months of deferiprone treatment. |
| BG001 | DFP-DFP |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Adverse Events | Safety and tolerability were assessed based on changes in: frequency of adverse events (AEs), frequency of serious adverse events (SAEs), and discontinuation due to AEs. No statistical comparison between the groups was conducted as all participants received the same study product. | Safety population | Posted | Count of Participants | Participants | 18 months |
|
Safety data were collected from the time of first dose until the end of the study (up to 18 months)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Patients | All participants received deferiprone during the extension study |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (21.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemias | Blood and lymphatic system disorders | MedDRA (21.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Fernando Tricta, MD | Chiesi Canada Corp. | 416--558-6342 | f.tricta@chiesi.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 9, 2018 | Apr 10, 2019 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Aug 20, 2014 | Apr 12, 2019 | Prot_001.pdf |
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| ID | Term |
|---|---|
| D006211 | Pantothenate Kinase-Associated Neurodegeneration |
| ID | Term |
|---|---|
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000077543 | Deferiprone |
| D007531 | Isoflurophate |
| ID | Term |
|---|---|
| D011728 | Pyridones |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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All participants in this study received the same intervention.
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| Baseline and Month 18 of each study |
| Change in Score on the BAD Scale -- Comparison of Placebo-DFP Patients Across Studies | The Barry-Albright Dystonia (BAD) scale is an instrument for rating the severity of dystonia in eight body regions. The individual scores are summed to provide a total score that ranges from 0 to 32; the higher the score, the more severe the dystonia. Patients were assessed for the change in total BAD score over the course of each study. | Baseline and Month 18 of each study |
| Change in Score on the BAD Scale -- Comparison of DFP-DFP Patients Across Studies | The Barry-Albright Dystonia (BAD) scale is an instrument for rating the severity of dystonia in eight body regions. The individual scores are summed to provide a total score that ranges from 0 to 32; the higher the score, the more severe the dystonia. Patients were assessed for the change in total BAD score over the course of the study. | Baseline and Month 18 of each study |
| Proportion of Patients With Improved or Unchanged BAD Score | Patients were deemed to be responders if their BAD total score either improved or remained unchanged from baseline, with baseline being the start of each study for the placebo-DFP group and the start of the initial study for the DFP-DFP group | Month 18 of each study |
| Patient Global Impression of Improvement (PGI-I) Comparison of Placebo-DFP Patients Across Studies | The Patient Global Impression of Improvement (PGI-I) is a global index used to rate the response of a condition to a therapy. Patients were asked at each post-baseline visit to rate their overall condition since the start of the extension study on a 7-point rating scale: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. | Month 18 of each study |
| Munich |
| 80336 |
| Germany |
| Foundation Neurological Institute C. Besta | Milan | 20133 | Italy |
| Newcastle University Institute of Human Genetics | Newcastle upon Tyne | NE1 3BZ | United Kingdom |
| Lost to Follow-up |
|
| Worsening of disease |
|
| Unable to comply with study requirements |
|
Patients who received 18 months of deferiprone treatment in the TIRCON2012V1 study and continued to receive it in the extension study, so received up to 36 months of deferiprone treatment.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| BAD score at baseline | Scores on the Barry-Albright Dystonia (BAD) scale at baseline of the initial study, prior to the start of treatment, and at baseline of the extension study, following 18 months of treatment with either placebo or deferiprone. Scores on the scale range from 0 to 32, with higher scores indicating more severe dystonia. | The baseline efficacy measurements are provided only for the 62 patients who provided at least one post-baseline efficacy assessment and were included in the efficacy analyses of the extension study. | Mean | Standard Deviation | units on a scale |
|
Patients in this group had been randomized to deferiprone treatment in the TIRCON2012V1 study and then continued on deferiprone in the extension study. Accordingly, they received up to 36 months of deferiprone treatment.
|
|
| Secondary | Change in Score on the BAD Scale -- Comparison of Treatment Groups Over Each Study | The Barry-Albright Dystonia (BAD) scale is an instrument for rating the severity of dystonia in eight body regions. The individual scores are summed to provide a total score that ranges from 0 to 32; the higher the score, the more severe the dystonia. Patients were assessed for the change in total BAD score over the course of both the initial study (during which one group received placebo and the other received deferiprone) and the extension study (during which both groups received deferiprone). | Posted | Mean | Standard Deviation | score on a scale | Baseline and Month 18 of each study |
|
|
|
|
| Secondary | Change in Score on the BAD Scale -- Comparison of Placebo-DFP Patients Across Studies | The Barry-Albright Dystonia (BAD) scale is an instrument for rating the severity of dystonia in eight body regions. The individual scores are summed to provide a total score that ranges from 0 to 32; the higher the score, the more severe the dystonia. Patients were assessed for the change in total BAD score over the course of each study. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Month 18 of each study |
|
|
|
|
| Secondary | Change in Score on the BAD Scale -- Comparison of DFP-DFP Patients Across Studies | The Barry-Albright Dystonia (BAD) scale is an instrument for rating the severity of dystonia in eight body regions. The individual scores are summed to provide a total score that ranges from 0 to 32; the higher the score, the more severe the dystonia. Patients were assessed for the change in total BAD score over the course of the study. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Month 18 of each study |
|
|
|
|
| Secondary | Proportion of Patients With Improved or Unchanged BAD Score | Patients were deemed to be responders if their BAD total score either improved or remained unchanged from baseline, with baseline being the start of each study for the placebo-DFP group and the start of the initial study for the DFP-DFP group | Posted | Count of Participants | Participants | Month 18 of each study |
|
|
|
|
| Secondary | Patient Global Impression of Improvement (PGI-I) Comparison of Placebo-DFP Patients Across Studies | The Patient Global Impression of Improvement (PGI-I) is a global index used to rate the response of a condition to a therapy. Patients were asked at each post-baseline visit to rate their overall condition since the start of the extension study on a 7-point rating scale: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. | Posted | Mean | Standard Deviation | score on a scale | Month 18 of each study |
|
|
|
|
| 2 |
| 68 |
| 33 |
| 68 |
| 66 |
| 68 |
| Cyanosis | Cardiac disorders | MedDRA (21.0) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (21.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Intestinal dilatation | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Oesophagitis | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Salivary hypersecretion | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Condition aggravated | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Medical device site inflammation | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Multiple organ dysfunction syndrome | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Obstruction | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Bacterial disease carrier | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Device related infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Infective glossitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Peritonitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Wound infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Chemical eye injury | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
|
| Clavicle fracture | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
|
| Toxicity to various agents | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
|
| Unintentional medical device removal | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
|
| Wound | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
|
| Device function test | Investigations | MedDRA (21.0) | Systematic Assessment |
|
| Physical examination | Investigations | MedDRA (21.0) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (21.0) | Systematic Assessment |
|
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
|
| Dystonia | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Hyporesponsive to stimuli | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Loss of consciousness | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Oromandibular dystonia | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Device dislocation | Product Issues | MedDRA (21.0) | Systematic Assessment |
|
| Device malfunction | Product Issues | MedDRA (21.0) | Systematic Assessment |
|
| Device stimulation issue | Product Issues | MedDRA (21.0) | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
|
| Urinary bladder rupture | Renal and urinary disorders | MedDRA (21.0) | Systematic Assessment |
|
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Choking | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Respiratory disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Colostomy closure | Surgical and medical procedures | MedDRA (21.0) | Systematic Assessment |
|
| Dental operation | Surgical and medical procedures | MedDRA (21.0) | Systematic Assessment |
|
| Gastrointestinal tube insertion | Surgical and medical procedures | MedDRA (21.0) | Systematic Assessment |
|
| Gastrostomy | Surgical and medical procedures | MedDRA (21.0) | Systematic Assessment |
|
| Hip surgery | Surgical and medical procedures | MedDRA (21.0) | Systematic Assessment |
|
| Intrathecal pump insertion | Surgical and medical procedures | MedDRA (21.0) | Systematic Assessment |
|
| Jejunostomy | Surgical and medical procedures | MedDRA (21.0) | Systematic Assessment |
|
| Medical device battery replacement | Surgical and medical procedures | MedDRA (21.0) | Systematic Assessment |
|
| Medical device change | Surgical and medical procedures | MedDRA (21.0) | Systematic Assessment |
|
| Medical device implantation | Surgical and medical procedures | MedDRA (21.0) | Systematic Assessment |
|
| Medical device removal | Surgical and medical procedures | MedDRA (21.0) | Systematic Assessment |
|
| Tracheostomy | Surgical and medical procedures | MedDRA (21.0) | Systematic Assessment |
|
| Tracheostomy tube removal | Surgical and medical procedures | MedDRA (21.0) | Systematic Assessment |
|
| Wound treatment | Surgical and medical procedures | MedDRA (21.0) | Systematic Assessment |
|
| Thrombosis | Vascular disorders | MedDRA (21.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Condition aggravated | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
|
| Laceration | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
|
| Body temperature increased | Investigations | MedDRA (21.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA (21.0) | Systematic Assessment |
|
| Serum ferritin decreased | Investigations | MedDRA (21.0) | Systematic Assessment |
|
| Iron deficiency | Metabolism and nutrition disorders | MedDRA (21.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
|
| Pain in extremity | Metabolism and nutrition disorders | MedDRA (21.0) | Systematic Assessment |
|
| Aphasia | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Ataxia | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Balance disorder | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Dystonia | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Systematic Assessment |
|
Sponsor retained title to and the right to publish all documentation, records, raw data, specimens or other work product generated in connection with the trial. Such publications shall not be made without the prior written consent of Sponsor. Neither Party will use the other Party's name in connection with any publication or promotion without the other Party's prior written consent. However, Sponsor has the right to publish appropriate information in order to satisfy regulatory requirements.
| D019150 | Neuroaxonal Dystrophies |
| D009069 | Movement Disorders |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D063066 |
| Organofluorophosphonates |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| t-test, 2 sided |
| 0.9781 |
| Superiority |
| t-test, 2 sided |
| 0.5885 |
| Superiority |