Efficacy of Epoetin Alfa in Patients With Friedreich's Ataxia

Friedreich's Ataxia Clinical Trial

Official title:

Single-Center, Open-Label, Sequential Trial to Test the Efficacy, Safety and Tolerability of Epoetin Alfa in Patients With Friedreich's Ataxia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00631202
• Other study ID #: FA_EPO_3
• Status: Completed
• Phase: Phase 2
• First received: February 28, 2008
• Last updated: May 26, 2010
• Start date: February 2008
• Est. completion date: June 2009

Study information

• Verified date: May 2010
• Source: Federico II University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

Friedreich's ataxia is a rare genetic disorder characterized by severe neurological disability and cardiomyopathy. Friedreich's ataxia is the consequence of frataxin deficiency. Although several drugs have been proposed, there is no available treatment. It was recently demonstrated that erythropoietin can increase the intracellular levels of frataxin in an in-vitro model.

The present project is aimed at testing the possible therapeutic approach of erythropoietin, which is an already available and commercialized drug. The investigators will perform both in-vitro and in-vivo tests, in order to asses its efficacy and safety in patients. The results will be useful to plan further clinical trials.

Description:

Friedreich ataxia (FRDA) is an inherited recessive disorder characterized by progressive neurological disability. FRDA is the consequence of frataxin deficiency. Although several drugs have been proposed for FRDA, there is no available treatment. Recently it was shown that recombinant human erythropoietin (rhu-EPO) administration increases frataxin expression in cultured human lymphocytes of FRDA patients. It is therefore of primary importance to test extensively rhu-EPO's ability in increasing frataxin levels in-vitro and in-vivo. In addition rhu-EPO is an already available and commercialized drug approved for the treatment of anaemia associated with chronic renal disease, heart failure and cancer. Towards this overall purpose, we will perform an acute clinical trial in FRDA patients with rhu-EPO and will assess its effect in-vivo on frataxin expression. In addition, rhu-EPO's safety in FRDA patients based on laboratory parameters and neurological indexes will be tested. The results will be useful to gain new insight in the role of rhu-EPO in FRDA, and in the future, it may be useful to plan further clinical trials.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: June 2009
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Molecular diagnosis of FA based on a homozygous GAA expansion within the FRDA with a triplet repeat sequence in the pathological range.

• Age >18, <50 years

Exclusion Criteria:

• Failure to meet one of the inclusion criteria

• Patients in treatment with Idebenone

• Wheelchair bound patients

• Significant renal, hepatic or haematological disease

• Positive history for arterial or venous thrombosis

• Acute diseases that might interfere with the study

• Positive history for arterial hypertension

• Present or programmed pregnancy

• Known hypersensitivity to study drug

• Other unacceptable concomitant medications (in particular agents thought to have a neuroprotective potential as tocopherol, amantadine, memantine, free radical scavengers).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Epoetin alfa
Patients that will satisfy all inclusion/exclusion criteria will be sequentially treated with three single Epoetin alfa administrations. The first time the dose will be 600U/KG BW s.c. in a single administration. The outcome measures will be assessed. A washout period of 1 month will be necessary to eliminate any carry-over effect. A second administration of 1200U/KG BW s.c. will be performed. Outcome measures will be again assessed.

Locations

Country	Name	City	State
Italy	Dipartimento di Scienze Neurologiche	Naples

Sponsors (1)

Lead Sponsor	Collaborator
Federico II University

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary endpoint will be the frataxin level in PBMCs from patients at different timing from a single Epoetin alfa administration.		0, 24, 48, 96 hours; 7, 15, 30, 60 days	No
Secondary	Echocardiography: Strain and strain rate after EPO administration at the highest study dose		0, 30 days	Yes
Secondary	Safety laboratory parameters, adverse events and tolerability		0, 7, 15, 30, 60 days	Yes
Secondary	International cooperative ataxia rating scale (ICARS).		0, 7, 30 days	Yes

External Links

•   Italian Ataxia association
•   University Federico II - Naples
•   University Federico II Clinics