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Trial record 5 of 6 for:    Neurodegeneration with Brain Iron Accumulation (NBIA)

Long-term Deferiprone Treatment in Patients With Pantothenate Kinase-Associated Neurodegeneration (TIRCON-EXT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02174848
Recruitment Status : Completed
First Posted : June 26, 2014
Results First Posted : July 17, 2019
Last Update Posted : July 17, 2019
Sponsor:
Information provided by (Responsible Party):
ApoPharma

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pantothenate Kinase-Associated Neurodegeneration
Intervention Drug: Deferiprone oral solution
Enrollment 68
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo-DFP DFP-DFP
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 24 44
Provided Post-baseline Efficacy Data 19 43
Completed 17 38
Not Completed 7 6
Reason Not Completed
Adverse Event             2             1
Withdrawal by Subject             3             3
Lost to Follow-up             0             1
Worsening of disease             1             1
Unable to comply with study requirements             1             0
Arm/Group Title Placebo-DFP DFP-DFP Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 24 44 68
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants 44 participants 68 participants
19.9  (13.0) 22.4  (9.6) 21.5  (10.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 44 participants 68 participants
Female
14
  58.3%
16
  36.4%
30
  44.1%
Male
10
  41.7%
28
  63.6%
38
  55.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 44 participants 68 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   4.2%
3
   6.8%
4
   5.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
22
  91.7%
41
  93.2%
63
  92.6%
More than one race
1
   4.2%
0
   0.0%
1
   1.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Number of Participants With Adverse Events
Hide Description 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.
Time Frame 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Placebo-DFP DFP-DFP
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 24 44
Measure Type: Count of Participants
Unit of Measure: Participants
Number of patients with at least one AE
22
  91.7%
42
  95.5%
Number of patients with at least one SAE
12
  50.0%
14
  31.8%
Number of patients who withdrew due to an AE
2
   8.3%
1
   2.3%
2.Secondary Outcome
Title Change in Score on the BAD Scale -- Comparison of Treatment Groups Over Each Study
Hide Description 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).
Time Frame Baseline and Month 18 of each study
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo-DFP DFP-DFP
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 19 43
Mean (Standard Deviation)
Unit of Measure: score on a scale
Change in BAD score over initial study 4.4  (4.8) 1.9  (3.2)
Change in BAD score over extension study 1.4  (3.7) 1.4  (2.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo-DFP, DFP-DFP
Comments This comparison is for the initial study, during which patients in the placebo-DFP group received placebo and patients in the DFP-DFP group received deferiprone.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0500
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo-DFP, DFP-DFP
Comments This comparison is for the extension study, during which patients in both groups received deferiprone.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9781
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
3.Secondary Outcome
Title Change in Score on the BAD Scale -- Comparison of Placebo-DFP Patients Across Studies
Hide Description 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.
Time Frame Baseline and Month 18 of each study
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo-DFP in Initial Study Placebo-DFP in Extension Study
Hide Arm/Group Description:
During the initial study, patients in the placebo-DFP group received 18 months of treatment with placebo
During the extension study, patients in the placebo-DFP group received up to 18 months of treatment with deferiprone
Overall Number of Participants Analyzed 19 19
Mean (Standard Deviation)
Unit of Measure: score on a scale
4.4  (4.8) 1.4  (3.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo-DFP in Initial Study, Placebo-DFP in Extension Study
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9781
Comments [Not Specified]
Method paired t-test
Comments [Not Specified]
4.Secondary Outcome
Title Change in Score on the BAD Scale -- Comparison of DFP-DFP Patients Across Studies
Hide Description 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.
Time Frame Baseline and Month 18 of each study
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DFP-DFP Group in Initial Study DFP-DFP Group in Extension Study
Hide Arm/Group Description:
During the initial study, patients in the DFP-DFP group received 18 months of treatment with deferiprone
During the extension study, patients in the DFP-DFP group received up to an additional 18 months of treatment with deferiprone
Overall Number of Participants Analyzed 43 43
Mean (Standard Deviation)
Unit of Measure: score on a scale
1.9  (3.2) 1.4  (2.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DFP-DFP Group in Initial Study, DFP-DFP Group in Extension Study
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2684
Comments [Not Specified]
Method paired t-test
Comments [Not Specified]
5.Secondary Outcome
Title Proportion of Patients With Improved or Unchanged BAD Score
Hide Description 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
Time Frame Month 18 of each study
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo-DFP DFP-DFP
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 19 43
Measure Type: Count of Participants
Unit of Measure: Participants
Completion of initial study
3
  15.8%
17
  39.5%
Completion of 18 months of deferiprone treatment
9
  47.4%
17
  39.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo-DFP, DFP-DFP
Comments This comparison is for the initial study, during which patients in the placebo-DFP group received placebo and patients in the DFP-DFP group received deferiprone
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0821
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo-DFP, DFP-DFP
Comments For the placebo-DFP group, the comparison is of the scores at the start vs. the end of the extension study; for the DFP-DFP group, the comparison is of the scores at the start vs. the end of the initial study
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5885
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
6.Secondary Outcome
Title Patient Global Impression of Improvement (PGI-I) Comparison of Placebo-DFP Patients Across Studies
Hide Description 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.
Time Frame Month 18 of each study
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo-DFP in Initial Study Placebo-DFP in Extension Study
Hide Arm/Group Description:
During the initial study, patients in the placebo-DFP group received 18 months of treatment with placebo
During the extension study, patients in the placebo-DFP group received up to 18 months of treatment with deferiprone
Overall Number of Participants Analyzed 19 19
Mean (Standard Deviation)
Unit of Measure: score on a scale
4.4  (1.5) 4.7  (1.4)
7.Secondary Outcome
Title Patient Global Impression of Improvement (PGI-I) Comparison of DFP-DFP Patients Across Studies
Hide Description 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.
Time Frame Month 18 of each study
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DFP-DFP Group in Initial Study DFP-DFP Group in Extension Study
Hide Arm/Group Description:
During the initial study, patients in the DFP-DFP group received 18 months of treatment with deferiprone
During the extension study, patients in the DFP-DFP group received up to an additional 18 months of treatment with deferiprone
Overall Number of Participants Analyzed 43 43
Mean (Standard Deviation)
Unit of Measure: score on a scale
4.4  (1.3) 4.1  (1.4)
8.Secondary Outcome
Title Proportion of Patients With Improved or Unchanged PGI-I Score
Hide Description Patients were deemed to be responders if their PGI-I score at the end of the study indicated that they felt they had either improved or remained unchanged from baseline
Time Frame Month 18 of each study
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo-DFP DFP-DFP
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 19 43
Measure Type: Count of Participants
Unit of Measure: Participants
End of initial study
7
  36.8%
23
  53.5%
End of extension study
10
  52.6%
28
  65.1%
Time Frame Safety data were collected from the time of first dose until the end of the study (up to 18 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title All Patients
Hide Arm/Group Description All participants received deferiprone during the extension study
All-Cause Mortality
All Patients
Affected / at Risk (%)
Total   2/68 (2.94%)    
Show Serious Adverse Events Hide Serious Adverse Events
All Patients
Affected / at Risk (%) # Events
Total   33/68 (48.53%)    
Blood and lymphatic system disorders   
Neutropenia  1  4/68 (5.88%)  7
Cardiac disorders   
Cyanosis  1  1/68 (1.47%)  1
Tachycardia  1  1/68 (1.47%)  1
Gastrointestinal disorders   
Constipation  1  1/68 (1.47%)  1
Gastritis  1  1/68 (1.47%)  1
Intestinal dilatation  1  1/68 (1.47%)  1
Intestinal obstruction  1  1/68 (1.47%)  1
Oesophagitis  1  1/68 (1.47%)  1
Salivary hypersecretion  1  1/68 (1.47%)  1
Vomiting  1  1/68 (1.47%)  1
General disorders   
Condition aggravated  1  1/68 (1.47%)  1
Medical device site inflammation  1  1/68 (1.47%)  1
Multiple organ dysfunction syndrome  1  1/68 (1.47%)  1
Obstruction  1  1/68 (1.47%)  1
Pyrexia  1  3/68 (4.41%)  3
Infections and infestations   
Bacterial disease carrier  1  1/68 (1.47%)  1
Bronchitis  1  2/68 (2.94%)  2
Device related infection  1  1/68 (1.47%)  1
Infective glossitis  1  1/68 (1.47%)  1
Peritonitis  1  1/68 (1.47%)  1
Pneumonia  1  2/68 (2.94%)  3
Respiratory tract infection  1  1/68 (1.47%)  1
Urinary tract infection  1  1/68 (1.47%)  1
Viral infection  1  1/68 (1.47%)  1
Wound infection  1  2/68 (2.94%)  2
Injury, poisoning and procedural complications   
Chemical eye injury  1  1/68 (1.47%)  1
Clavicle fracture  1  1/68 (1.47%)  1
Toxicity to various agents  1  1/68 (1.47%)  1
Unintentional medical device removal  1  1/68 (1.47%)  1
Wound  1  1/68 (1.47%)  1
Investigations   
Device function test  1  1/68 (1.47%)  1
Physical examination  1  1/68 (1.47%)  1
Weight decreased  1  1/68 (1.47%)  1
Musculoskeletal and connective tissue disorders   
Bursitis  1  1/68 (1.47%)  1
Nervous system disorders   
Headache  1  1/68 (1.47%)  1
Hyporesponsive to stimuli  1  1/68 (1.47%)  1
Loss of consciousness  1  1/68 (1.47%)  1
Oromandibular dystonia  1  1/68 (1.47%)  1
Somnolence  1  1/68 (1.47%)  1
Syncope  1  1/68 (1.47%)  1
Product Issues   
Dystonia  1  8/68 (11.76%)  8
Device dislocation  1  1/68 (1.47%)  1
Device malfunction  1  1/68 (1.47%)  1
Device stimulation issue  1  1/68 (1.47%)  1
Psychiatric disorders   
Agitation  1  1/68 (1.47%)  2
Renal and urinary disorders   
Urinary bladder rupture  1  1/68 (1.47%)  1
Respiratory, thoracic and mediastinal disorders   
Aspiration  1  1/68 (1.47%)  1
Choking  1  1/68 (1.47%)  1
Cough  1  1/68 (1.47%)  1
Pneumonia aspiration  1  1/68 (1.47%)  1
Pneumothorax  1  1/68 (1.47%)  1
Respiratory disorder  1  1/68 (1.47%)  1
Respiratory failure  1  1/68 (1.47%)  1
Surgical and medical procedures   
Colostomy closure  1  1/68 (1.47%)  1
Dental operation  1  1/68 (1.47%)  1
Gastrointestinal tube insertion  1  1/68 (1.47%)  1
Gastrostomy  1  4/68 (5.88%)  4
Hip surgery  1  1/68 (1.47%)  1
Intrathecal pump insertion  1  1/68 (1.47%)  1
Jejunostomy  1  1/68 (1.47%)  1
Medical device battery replacement  1  2/68 (2.94%)  2
Medical device change  1  2/68 (2.94%)  2
Medical device implantation  1  3/68 (4.41%)  3
Medical device removal  1  1/68 (1.47%)  1
Tracheostomy  1  1/68 (1.47%)  5
Tracheostomy tube removal  1  1/68 (1.47%)  1
Wound treatment  1  1/68 (1.47%)  1
Vascular disorders   
Thrombosis  1  1/68 (1.47%)  2
1
Term from vocabulary, MedDRA (21.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
All Patients
Affected / at Risk (%) # Events
Total   66/68 (97.06%)    
Blood and lymphatic system disorders   
Anemias  1  12/68 (17.65%)  27
Gastrointestinal disorders   
Abdominal pain upper  1  8/68 (11.76%)  16
Diarrhoea  1  4/68 (5.88%)  6
Dysphagia  1  8/68 (11.76%)  8
Nausea  1  5/68 (7.35%)  5
Vomiting  1  10/68 (14.71%)  13
General disorders   
Condition aggravated  1  17/68 (25.00%)  25
Pain  1  5/68 (7.35%)  5
Pyrexia  1  20/68 (29.41%)  64
Infections and infestations   
Bronchitis  1  6/68 (8.82%)  30
Influenza  1  4/68 (5.88%)  4
Nasopharyngitis  1  11/68 (16.18%)  22
Upper respiratory tract infection  1  13/68 (19.12%)  19
Urinary tract infection  1  6/68 (8.82%)  8
Injury, poisoning and procedural complications   
Contusion  1  5/68 (7.35%)  5
Laceration  1  8/68 (11.76%)  20
Investigations   
Body temperature increased  1  4/68 (5.88%)  4
Neutrophil count decreased  1  10/68 (14.71%)  26
Serum ferritin decreased  1  18/68 (26.47%)  25
Metabolism and nutrition disorders   
Iron deficiency  1  11/68 (16.18%)  11
Pain in extremity  1  14/68 (20.59%)  26
Musculoskeletal and connective tissue disorders   
Arthralgia  1  11/68 (16.18%)  12
Back pain  1  4/68 (5.88%)  4
Muscle spasms  1  8/68 (11.76%)  11
Nervous system disorders   
Aphasia  1  5/68 (7.35%)  6
Ataxia  1  4/68 (5.88%)  4
Balance disorder  1  5/68 (7.35%)  5
Dystonia  1  32/68 (47.06%)  74
Headache  1  19/68 (27.94%)  64
Somnolence  1  6/68 (8.82%)  8
Tremor  1  4/68 (5.88%)  7
Psychiatric disorders   
Agitation  1  5/68 (7.35%)  13
Respiratory, thoracic and mediastinal disorders   
Cough  1  12/68 (17.65%)  19
Oropharyngeal pain  1  10/68 (14.71%)  11
Rhinorrhoea  1  6/68 (8.82%)  8
Skin and subcutaneous tissue disorders   
Rash  1  5/68 (7.35%)  5
1
Term from vocabulary, MedDRA (21.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Caroline Fradette
Organization: ApoPharma Inc.
Phone: 416-401-7543
EMail: cfradett@apopharma.com
Layout table for additonal information
Responsible Party: ApoPharma
ClinicalTrials.gov Identifier: NCT02174848     History of Changes
Other Study ID Numbers: TIRCON2012V1-EXT
2012-000845-11 ( EudraCT Number )
First Submitted: June 5, 2014
First Posted: June 26, 2014
Results First Submitted: May 1, 2019
Results First Posted: July 17, 2019
Last Update Posted: July 17, 2019