Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01016366
Recruitment Status : Completed
First Posted : November 19, 2009
Last Update Posted : November 8, 2016
Information provided by (Responsible Party):
H. Lundbeck A/S

Brief 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.

Condition or disease Intervention/treatment Phase
Friedreich's Ataxia Drug: Lu AA24493 Drug: Placebo Phase 2

Detailed 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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
Study Start Date : October 2009
Actual Primary Completion Date : March 2011
Actual Study Completion Date : April 2011

Arm Intervention/treatment
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 Drug: Placebo
Vials with solution for i.v. injection. Placebo dosed 3 times per week for two weeks.

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. To explore biomarkers of efficacy, including frataxin, 8-OHdG & peroxides [ Time Frame: 2 week treatment phase + 4 week follow up period ]
  2. 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 ]
  3. To explore efficacy by the Clinical Global Impression scales (CGI-I/S) [ Time Frame: 2 week treatment phase + 4 week follow up period ]
  4. To explore population pharmacokinetic parameters of Lu AA24493 [ Time Frame: 2 week treatment phase + 4 week follow up period ]
  5. To evaluate the immunogenicity of Lu AA24493 [ Time Frame: 2 week treatment phase + 4 week follow up period ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01016366

Layout table for location information
Innsbruck, Austria, 6020
Bochum, Germany, 44791
Bonn, Germany, 53127
Munich, Germany, 80336
Tuebingen, Germany, 72026
Milano, Italy, 20133
Naples, Italy, 80131
Sponsors and Collaborators
H. Lundbeck A/S
Layout table for investigator information
Study Director: Email contact via H. Lundbeck A/S
Study Data/Documents: EMA EudraCT Results  This link exits the site
Identifier: 2008-003662-25

Layout table for additonal information
Responsible Party: H. Lundbeck A/S Identifier: NCT01016366    
Other Study ID Numbers: 12631A
2008-003662-25 ( EudraCT Number )
First Posted: November 19, 2009    Key Record Dates
Last Update Posted: November 8, 2016
Last Verified: November 2016
Keywords provided by H. Lundbeck A/S:
Friedreich's Ataxia
Additional relevant MeSH terms:
Layout table for MeSH terms
Cerebellar Ataxia
Friedreich Ataxia
Neurologic Manifestations
Nervous System Diseases
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Spinocerebellar Degenerations
Spinal Cord Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Mitochondrial Diseases
Metabolic Diseases