Safety Study of Carbamylated Erythropoietin to Treat Patients With the Neurodegenerative Disorder Friedreich's Ataxia
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Randomised, Double Blind, Placebo Controlled Study of Lu AA24493 in Patients With Friedreich's Ataxia to Evaluate Safety and Tolerability and to Explore Efficacy|
- To evaluate the safety and tolerability of 2 weeks treatment with Lu AA24493 in patients with Friedreich's Ataxia [ Time Frame: 2 week treatment phase + 4 week follow up period ]
- To explore biomarkers of efficacy, including frataxin, 8-OHdG & peroxides [ Time Frame: 2 week treatment phase + 4 week follow up period ]
- To explore efficacy by neurological assessment (Scale for the Assessment and Rating of Ataxia (SARA), Friedreich's Ataxia Rating Scale (FARS)) [ Time Frame: 2 week treatment phase + 4 week follow up period ]
- To explore efficacy by the Clinical Global Impression scales (CGI-I/S) [ Time Frame: 2 week treatment phase + 4 week follow up period ]
- To explore population pharmacokinetic parameters of Lu AA24493 [ Time Frame: 2 week treatment phase + 4 week follow up period ]
- To evaluate the immunogenicity of Lu AA24493 [ Time Frame: 2 week treatment phase + 4 week follow up period ]
|Study Start Date:||October 2009|
|Study Completion Date:||April 2011|
|Primary Completion Date:||March 2011 (Final data collection date for primary outcome measure)|
|Experimental: Lu AA24493||
Drug: Lu AA24493
Vials with solution for i.v. injection. 325mcg Lu AA24493 dosed 3 times per week for two weeks. Vials will be supplied in concentrations ready for injection.
Other Name: CEPO
|Placebo Comparator: Placebo||
Vials with solution for i.v. injection. Placebo dosed 3 times per week for two weeks.
Friedreich's Ataxia (FRDA) is a hereditary, progressive neurodegenerative disorder caused by mutations in the gene encoding frataxin. The mutation results in a severe reduction in levels of the mitochondrial protein, frataxin. A decline in frataxin levels and its associated consequences is believed to be the primary cause of symptoms in FRDA patients. The clinical symptoms of FRDA include progressive gait and limb ataxia, dysarthria, diabetes mellitus and hypertrophic cardiomyopathy. First symptoms usually appear between the age of 5 and 15 years. As the disease progresses the patient becomes confined to a wheel chair and at later stages the patients become increasingly incapacitated. There is currently no effective treatment for FRDA.
The naturally occurring hormone, erythropoietin (EPO), is able to protect various neuronal tissues from ischemic injury. Recombinant human erythropoietin (EPO) increases frataxin expression in lymphocytes from patients with FRDA. Also, EPO treatment of FRDA patients resulted in a favourable outcome compared to baseline as assessed by the levels of frataxin and biomarkers of oxidative stress. In a pilot study with EPO in FRDA patients, the treatment was well tolerated apart from the expected haematological (haematopoietic) side effects. Lu AA24493 (CEPO) is a modified (carbamylated) version of EPO, which is neuroprotective but without the haematopoietic side effects. Lu AA24493 is being developed for treatment of patients with FRDA.
Although the target for the non-haematological effects of Lu AA24493 (and EPO) is currently unknown, Lu AA24493 (CEPO) can protect cells and tissue from various types of injuries. Furthermore, in vitro Lu AA24493 (CEPO) increases the frataxin levels in lymphocytes from FRDA patients as well as from control patients. This study aims to evaluate the safety of 2 weeks treatment (6 doses, 3 doses per week) of CEPO in patients with FRDA and to explore efficacy by using neurological rating scales and by exploring levels of frataxin and biomarkers of oxidative stress.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01016366
|Innsbruck, Austria, 6020|
|Bochum, Germany, 44791|
|Bonn, Germany, 53127|
|Munich, Germany, 80336|
|Tuebingen, Germany, 72026|
|Milano, Italy, 20133|
|Naples, Italy, 80131|
|Study Director:||Email contact via H. Lundbeck A/S||LundbeckClinicalTrials@lundbeck.com|