Pantothenate Kinase-Associated Neurodegeneration (PKAN) MedDRA version: 16.0 Level: PT Classification code 10053643 Term: Neurodegenerative disorder System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Ferriprox
Product Name: Deferiprone 80 mg/mL oral solution (Ferriprox)
Pharmaceutical Form: Oral solution
INN or Proposed INN: Deferiprone
Sponsors
ApoPharma Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Males and females 4 years of age and older at screening visit; 2.Patients must have PKAN, confirmed by genetic testing; 3.Patients having a BAD total score > = 3 at the screening visit; 4.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 2 months prior to the screening visit and stimulation parameters / pump settings must remain stable for the duration of the trial. Enrollment of non-DBS patients will be given priority in order to ensure the majority can undergo imaging; 5. Potentially sexually active female patients of childbearing potential must have a negative pregnancy test result at Screening Visit (if applicable; in cases where the Investigator determines there is no reasonable risk of pregnancy because of significant incapacity, pregnancy testing will not be performed); 6.Fertile potentially sexually active males must use an effective method of contraception or must confirm partner’s use of effective contraception; 7.Informed consent/assent obtained before any study-related activities are undertaken; 8.Ability and willingness to adhere to the protocol including appointments and evaluation schedule. Are the trial subjects under 18? yes Number of subjects for this age range: 72 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 18 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1.Evidence of iron deficiency defined by Fe:TIBC ratio 3 times upper limit of normal at screening) or abnormal creatinine levels at screening visit; 5.Disorders associated with neutropenia (absolute neutrophil count (ANC) < 1.5 x 109/L) or thrombocytopenia (platelet count < 50 x 109/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 ANC has fully recovered at the screening visit; 6.Pregnant, breastfeeding, or planning to become pregnant during the study; 7.Initiation or discontinuation of treatment with baclofen, trihexyphenidyl, clonazepam, tizanidine within 30 days prior to baseline; and initiation or discontinuation of treatment with tetrabenazine within 90 days prior to baseline; 8. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the baseline; 9. Currently taking iron chelators; 10.Patients who, in the opinion of the physician, represent a high medical or psychological risk; 11. History of or active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements; 12.Patients and patient's legal representative (if applicable) with a mental incapacity, unwillingness or language barriers precluding adequate understanding or co-operation. 13.Baclofen pump placement less than two months prior to the beginning of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The Co Primary objectives 1- To evaluate the change in severity of dystonia (BAD scale) in patients with PKAN treated with deferiprone for 18 months compared to placebo. 2- To evaluate the patient's global impression of condition's improvement in patients treated with deferiprone for 18 months compared to placebo (PGI-I) The study will be considered positive if both co-primary endpoints reach statistical significance. ; Secondary Objective: The secondary objectives are: 1- To evaluate the effect of deferiprone compared to placebo in the change in globus pallidus iron levels (MRI) (subset of patients); 2- To evaluate the effect of deferiprone compared to placebo on the change in motor symptoms (UPDRS); 3- To evaluate the effect of deferiprone compared to placebo on a measure of functional independence (WeeFIM or FIM); 4- To evaluate the effect of deferiprone compared to placebo on quality of life (PedsQL); 5- To evaluate the effect of deferiprone compared to placebo on the patient's quality of sleep (PSQI); 6- To evaluate the pharmacokinetics of deferiprone and its 3-?- glucuronide metabolite (subset of patients); 7- To evaluate the safety and tolerability of deferiprone in patients with PKAN. ; Primary end point(s): 1) Change in the Barry-Albright Dystonia Scale (BAD) total score from baseline to Month 18 in patients treated with deferiprone compared to placebo, as assessed by central blinded evaluation of video-tapes; 2) Patient's Global Impression of Improvement (PGI-I) from baseline to Month 18 in patients treated with deferiprone compared to placebo. ; Timepoint(s) of evaluation of this end point: Timepoints: Baseline, 6m, 12m, 18m | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Proportion of patients with improved or unchanged BAD scale total score between baseline and Month 18 (responder analysis); 2) Change from baseline to Month 18 in BAD scale score per body region (eyes, mouth, neck, trunk, each upper and lower extremity), as assessed by central blinded evaluation of video-tapes; 3) Proportion of patients showing an improvement on PGI-I at the Month 18 visit (responder analysis); 4) Change from baseline to Month 18 in globus pallidus iron levels as measured by MRI R2* (subset of patients without deep brain stimulators who can tolerate MRI scan); 5) Change from baseline to Month 18 in UPDRS Parts I, II, III and VI scores, respectively; 6) Change from baseline to Month 18 in global WeeFIM score (Or FIM for patients > 18 years); 7) Change from baseline to Month 18 in WeeFIM (or FIM for patients >18 years) score per item; 8) Change from baseline to Month 18 in quality of life (PedsQL); 9) Change from baseline to Month 18 in quality of sleep (PSQI). Other secondary endpoints: Safety Endpoints: (1) Frequency of Adverse Events (AEs); (2) Frequency of Serious Adverse Events (SAEs); (3) Discontinuation due to AEs; (4) Hematology assessments; (5) Blood clinical biochemistry assessments; (6) ECG. Pharmacokinetic Endpoints: Steady state pharmacokinetics of deferiprone and its 3-O-glucuronide metabolite will be assessed in a subset of up to 24 patients over 12 hours. The following standard pharmacokinetic parameters will be derived from plasma concentrations of deferiprone: Cmax, Tmax, Cmin, AUCSS, CL/F, T1/2, Vd/F. ; Timepoint(s) of evaluation of this end point: Timepoints: Secondary endpoints: Baseline, 6m, 12m, 18m; except Brain MRI: Baseline and 18m. Safety endpoints: | — |
Countries
Germany, Italy, Poland, United Kingdom, United States
Contacts
Public ContactFernando Tricta
ApoPharma Inc
Outcome results
None listed