Pantothenate Kinase-Associated Neurodegeneration
Conditions
Keywords
Pantothenate Kinase-Associated Neurodegeneration, PKAN, Neurodegeneration with Brain Iron Accumulation, NBIA, Deferiprone, Ferriprox
Brief summary
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.
Detailed description
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.
Interventions
Deferiprone oral solution at a dosage of up to 15 mg per kilogram of body weight, twice a day
Sponsors
ApoPharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All participants in this study received the same intervention.
Eligibility
Sex/Gender
ALL
Age
5 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Completed study TIRCON2012V1
Exclusion criteria
* Withdrew from the study TIRCON2012V1 for reasons of safety * Plan to participate in another clinical trial at any time from the day of enrolment until 30 days post-treatment in the current study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | 18 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Score on the BAD Scale -- Comparison of Treatment Groups Over Each Study | Baseline and Month 18 of 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). |
| Change in Score on the BAD Scale -- Comparison of Placebo-DFP Patients Across Studies | Baseline and Month 18 of 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 each study. |
| Change in Score on the BAD Scale -- Comparison of DFP-DFP Patients Across Studies | Baseline and Month 18 of 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 the study. |
| Proportion of Patients With Improved or Unchanged BAD Score | Month 18 of each study | 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 |
| Patient Global Impression of Improvement (PGI-I) Comparison of Placebo-DFP Patients Across Studies | Month 18 of each study | 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. |
Countries
Germany, Italy, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 24 |
| DFP-DFP 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. | 44 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Unable to comply with study requirements | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 3 |
| Overall Study | Worsening of disease | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo-DFP | DFP-DFP | Total |
|---|---|---|---|
| Age, Continuous | 19.9 years STANDARD_DEVIATION 13 | 22.4 years STANDARD_DEVIATION 9.6 | 21.5 years STANDARD_DEVIATION 10.9 |
| BAD score at baseline BAD score at baseline of extension study | 20.4 units on a scale STANDARD_DEVIATION 8.2 | 21.3 units on a scale STANDARD_DEVIATION 7.6 | 21.0 units on a scale STANDARD_DEVIATION 7.7 |
| BAD score at baseline BAD score at baseline of initial study | 16.0 units on a scale STANDARD_DEVIATION 8 | 19.4 units on a scale STANDARD_DEVIATION 8.1 | 18.3 units on a scale STANDARD_DEVIATION 8.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 41 Participants | 63 Participants |
| Sex: Female, Male Female | 14 Participants | 16 Participants | 30 Participants |
| Sex: Female, Male Male | 10 Participants | 28 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 68 |
| other Total, other adverse events | 66 / 68 |
| serious Total, serious adverse events | 33 / 68 |
Outcome results
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.
Time frame: 18 months
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo-DFP | Number of Participants With Adverse Events | Number of patients with at least one AE | 22 Participants |
| Placebo-DFP | Number of Participants With Adverse Events | Number of patients with at least one SAE | 12 Participants |
| Placebo-DFP | Number of Participants With Adverse Events | Number of patients who withdrew due to an AE | 2 Participants |
| DFP-DFP | Number of Participants With Adverse Events | Number of patients with at least one AE | 42 Participants |
| DFP-DFP | Number of Participants With Adverse Events | Number of patients who withdrew due to an AE | 1 Participants |
| DFP-DFP | Number of Participants With Adverse Events | Number of patients with at least one SAE | 14 Participants |
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.
Time frame: Baseline and Month 18 of each study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-DFP | Change in Score on the BAD Scale -- Comparison of DFP-DFP Patients Across Studies | 1.9 score on a scale | Standard Deviation 3.2 |
| DFP-DFP | Change in Score on the BAD Scale -- Comparison of DFP-DFP Patients Across Studies | 1.4 score on a scale | Standard Deviation 2.4 |
p-value: 0.2684paired t-test
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.
Time frame: Baseline and Month 18 of each study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-DFP | Change in Score on the BAD Scale -- Comparison of Placebo-DFP Patients Across Studies | 4.4 score on a scale | Standard Deviation 4.8 |
| DFP-DFP | Change in Score on the BAD Scale -- Comparison of Placebo-DFP Patients Across Studies | 1.4 score on a scale | Standard Deviation 3.7 |
p-value: 0.0206paired t-test
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).
Time frame: Baseline and Month 18 of each study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo-DFP | Change in Score on the BAD Scale -- Comparison of Treatment Groups Over Each Study | Change in BAD score over initial study | 4.4 score on a scale | Standard Deviation 4.8 |
| Placebo-DFP | Change in Score on the BAD Scale -- Comparison of Treatment Groups Over Each Study | Change in BAD score over extension study | 1.4 score on a scale | Standard Deviation 3.7 |
| DFP-DFP | Change in Score on the BAD Scale -- Comparison of Treatment Groups Over Each Study | Change in BAD score over initial study | 1.9 score on a scale | Standard Deviation 3.2 |
| DFP-DFP | Change in Score on the BAD Scale -- Comparison of Treatment Groups Over Each Study | Change in BAD score over extension study | 1.4 score on a scale | Standard Deviation 2.4 |
Comparison: 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.p-value: 0.05t-test, 2 sided
Comparison: This comparison is for the extension study, during which patients in both groups received deferiprone.p-value: 0.9781t-test, 2 sided
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.
Time frame: Month 18 of each study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-DFP | Patient Global Impression of Improvement (PGI-I) Comparison of Placebo-DFP Patients Across Studies | 4.4 score on a scale | Standard Deviation 1.5 |
| DFP-DFP | Patient Global Impression of Improvement (PGI-I) Comparison of Placebo-DFP Patients Across Studies | 4.7 score on a scale | Standard Deviation 1.4 |
p-value: 0.3306t-test, 2 sided
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
Time frame: Month 18 of each study
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo-DFP | Proportion of Patients With Improved or Unchanged BAD Score | Completion of initial study | 3 Participants |
| Placebo-DFP | Proportion of Patients With Improved or Unchanged BAD Score | Completion of 18 months of deferiprone treatment | 9 Participants |
| DFP-DFP | Proportion of Patients With Improved or Unchanged BAD Score | Completion of 18 months of deferiprone treatment | 17 Participants |
| DFP-DFP | Proportion of Patients With Improved or Unchanged BAD Score | Completion of initial study | 17 Participants |
Comparison: 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 deferipronep-value: 0.0821t-test, 2 sided
Comparison: 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 studyp-value: 0.5885t-test, 2 sided