Pantothenate kinase-associated neurodegeneration (PKAN)
Conditions
Interventions
Product Name: Deferiprone 80 mg/mL oral solution
Pharmaceutical Form: Oral solution
INN or Proposed INN: Deferiprone
CAS Number: 30652-11-0
Current Sponsor code: V03AC02
Other descriptive name: Deferi
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 two months prior to the screening visit and every effort should be made to maintain the stable setting for the duration of the study: • Enrollment of non-DBS patients will be given priority, to maximize the proportion that can undergo imaging; 5. 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 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
Exclusion criteria
Exclusion criteria: 1. Evidence of iron deficiency defined by Fe:TIBC ratio 3 times upper limit of normal at screening) or clinically significant abnormal creatinine levels at screening visit; 5. Disorders associated with neutropenia (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 the ANC has fully recovered at the screening visit; 6. Pregnant or nursing females, females planning to become pregnant, and females of childbearing potential who are sexually active and are unwilling, or unable, to use an acceptable method of contraception according to local requirements; 7. Initiation or discontinuation of treatment with baclofen, trihexyphenidyl, clonazepam, tizanidine within 30 days prior to baseline; treatment with botox within 60 days of 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 visit; 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 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 beginningof the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To evaluate the change in severity of dystonia (BAD scale) in patients with PKAN treated with deferiprone for 18 months compared to placebo. - To evaluate the patient’s global impression of condition’s improvement in patients treated with deferiprone for 18 months compared to placebo (PGI-I). ;Secondary Objective: - To evaluate the effect of deferiprone compared to placebo on the change in globus pallidus iron levels (MRI) (subset of patients). - To evaluate the effect of deferiprone compared to placebo on motor symptoms (UPDRS); - To evaluate the effect of deferiprone compared to placebo on a measure of functional independence (WeeFIM or FIM); - To evaluate the effect of deferiprone compared to placebo on quality of life (PedsQL); - To evaluate the effect of deferiprone compared to placebo on the patient’s quality of sleep (PSQI); - To evaluate the pharmacokinetics of deferiprone and its 3-O-glucuronide metabolite (subset of patients); - To evaluate the safety and tolerability of deferiprone in patients with PKAN. ;Primary end point(s): Efficacy Endpoints: Co-Primary: - 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; - Patient’s Global Impression of Improvement (PGI-I) from baseline to Month 18 in patients treated with deferiprone compared to placebo. Study will be considered positive if both co-primary endpoints reach statistical significance.;Timepoint(s) of evaluation of this end point: BAD: Baseline, 6m, 12m, 18m. PGI-I: 6m, 12m, 18m. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy Endpoints: Secondary (deferiprone vs. placebo): 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). 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). 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 - T½ - Vd/F ;Timepoint(s) of evaluation of this end point: Secondary endpoints: Baseline, and 2m, 3m, 6m, 9m, 12m, 15m, 18m and follow-up; except Brain MRI: Baseline and 18m. Safety endpoints - Physical examination: at Screening, 1.5m, 3m, 6m, 12m,18m and Follow-up. - Hematology: at Screening, weekly after dosing starts, 1.5m, 3m, 6m, 12m,18m and Follow-up. - Biochemistry: at Screening, 1.5m, 3m, 6m, 12m, 18m. - ECG: at Screening and 18m. - Adverse | — |
Countries
Germany, Italy, Poland, United Kingdom, United States
Contacts
Public ContactJohn Connelly
ApoPharma Inc.
Outcome results
None listed