Safety Study of Carbamylated Erythropoietin to Treat Patients With the Neurodegenerative Disorder Friedreich's Ataxia

Friedreich's Ataxia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01016366
• Other study ID #: 12631A
• Secondary ID: 2008-003662-25
• Status: Completed
• Phase: Phase 2
• First received: November 18, 2009
• Last updated: November 7, 2016
• Start date: October 2009
• Est. completion date: April 2011

Study information

• Verified date: November 2016
• Source: H. Lundbeck A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Office for Safety in Health CareGermany: Federal Institute for Drugs and Medical DevicesItaly: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The primary purpose of the study is to determine whether carbamylated erythropoietin is a safe treatment for patients who suffer from Friedreich's Ataxia.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: April 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• The patient has been diagnosed with FRDA and has had a genetic test demonstrating >400 GAA nucleotide triplet repeats on the shorter of the two frataxin alleles

• The patient has a SARA (Stance) sub-score of <=6

• The patient has a SARA (Gait) sub-score of <=6

• Man or woman, aged 18 years or over

• If female then woman should agree not to try to become pregnant during the study, and use adequate protection/abstinence or not be of child bearing potential

Exclusion Criteria:

• Clinically significant unstable illnesses such as liver, kidney, heart, stomach problems unrelated to their disease of FRDA

• Disallowed medications

• Serious underlying disease

• Clinically significant abnormal vital signs unrelated to the underlying disease of FRDA

• Abnormal laboratory blood results considered by the doctor as clinically significant, e.g.anaemia

• Treatment with idebenone within 6 weeks prior to screening

• Treatment with erythropoietin within 16 weeks prior to screening

• Clinically significant abnormal ECG

• Received or donated blood within previous 3 months

• Participation within another clinical trial within past 30 days

• Pregnancy or breast feeding

• History of drug allergies or hypersensitivities

• Current (or within past 6 months) disorder related to drug or alcohol abuse (as defined DSM-IV-TR)

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ataxia
• Cerebellar Ataxia
• Friedreich Ataxia
• Friedreich's Ataxia

Intervention

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.
• Placebo
Vials with solution for i.v. injection. Placebo dosed 3 times per week for two weeks.

Locations

Country	Name	City	State
Austria	AT001	Innsbruck
Germany	DE004	Bochum
Germany	DE002	Bonn
Germany	DE001	Munich
Germany	DE003	Tuebingen
Italy	IT001	Milano
Italy	IT002	Naples

Sponsors (1)

Lead Sponsor	Collaborator
H. Lundbeck A/S

Countries where clinical trial is conducted

Austria,  Germany,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the safety and tolerability of 2 weeks treatment with Lu AA24493 in patients with Friedreich's Ataxia		2 week treatment phase + 4 week follow up period	Yes
Secondary	To explore biomarkers of efficacy, including frataxin, 8-OHdG & peroxides		2 week treatment phase + 4 week follow up period	No
Secondary	To explore efficacy by neurological assessment (Scale for the Assessment and Rating of Ataxia (SARA), Friedreich's Ataxia Rating Scale (FARS))		2 week treatment phase + 4 week follow up period	No
Secondary	To explore efficacy by the Clinical Global Impression scales (CGI-I/S)		2 week treatment phase + 4 week follow up period	No
Secondary	To explore population pharmacokinetic parameters of Lu AA24493		2 week treatment phase + 4 week follow up period	No
Secondary	To evaluate the immunogenicity of Lu AA24493		2 week treatment phase + 4 week follow up period	No