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Efficacy Study of Epoetin Alfa in Friedreich Ataxia (FRIEMAX)

This study has been completed.
Friedreich's Ataxia Research Alliance
Associazione Italiana per la lotta alle Sindromi Atassiche (AISA)
Information provided by (Responsible Party):
Alessandro Filla, Federico II University Identifier:
First received: December 15, 2011
Last updated: August 10, 2015
Last verified: August 2015
Friedreich's ataxia (FRDA) is a rare genetic disorder characterised 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. Four trials recently demonstrated that erythropoietin can increase the intracellular levels of frataxin. The present project is aimed at testing a long term therapeutic approach using erythropoietin, which is an already available and commercialised drug. The study will test the effect of erythropoietin on exercise capacity, which is reduced in patients with FRDA. Additional objectives of the study will be the drug's safety and tolerability, and its effect on frataxin, blood vessel reactivity, heart functional indexes, and disease progression.

Condition Intervention Phase
Friedreich Ataxia
Drug: Epoetin alfa
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Placebo-controlled, Clinical Trial to Test the Efficacy of Epoetin Alfa on Physical Performance of Friedreich Ataxia Patients.

Resource links provided by NLM:

Further study details as provided by Federico II University:

Primary Outcome Measures:
  • Peak oxygen uptake (VO2 max) at the cardiopulmonary exercise test (CPET) [ Time Frame: 48 weeks ]
    Patients will undergo a complete CPET as described in the methods section. CPET will be performed at baseline (Visit 2), at 24 weeks (Visit 5), and at 48 weeks (Visit 7).

Secondary Outcome Measures:
  • Secondary outcome variables at the CPET (anaerobic threshold, ventilatory efficiency, exercise duration, and power output). [ Time Frame: 24 and 48 weeks ]
  • Frataxin levels in peripheral blood mononuclear cells (PBMCs). [ Time Frame: all timepoints ]
  • Echocardiography [ Time Frame: 24, and 48 weeks ]
  • Vascular reactivity [ Time Frame: 24 and 48 weeks ]
    Vascular reactivity will be measured by the Flow-Mediated Dilation technique (FMD)

  • Neurological progression [ Time Frame: 24 and 48 weeks ]
    Neurological progression will be measured with the Scale for the Assessment and Rating of Ataxia (SARA), and with the 9 hole pegboard test (9-HPT)

  • Quality of life [ Time Frame: 24 and 48 weeks ]
    Quality of life will be assessed with the EQ-5D, ADL, and IADL scales

  • Safety and tolerability [ Time Frame: all visits ]
    Safety and tolerability will be assessed by recording all serious and non serious adverse events at all visits of the trial

Enrollment: 56
Study Start Date: January 2013
Study Completion Date: June 2015
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Epoetin alfa
Patients will be treated with Epoetin alfa 1200 IU/Kg s.c. every 12 weeks
Drug: Epoetin alfa
Epoetin alfa will be administered s.c. at 1200 IU/Kg every 12 weeks
Other Names:
  • EPREX 40000 IU
  • EPREX 10000 IU
Placebo Comparator: Placebo
Placebo 1200 IU/Kg s.c. every 12 weeks
Drug: Placebo

Detailed Description:

Friedreich's ataxia (FA) is an autosomal recessive ataxia caused by a trinucleotide GAA expansion in the first intron of the FXN gene. The gene encodes for a 210aa mitochondrial protein called frataxin, whose mRNA and protein levels are severely reduced in FA. It has been suggested that frataxin is involved in iron-sulphur cluster and heme biogenesis, iron binding/storage, and chaperone activity. Clinically, the age of onset is generally around puberty and, as the disease progresses, there is increasing ataxia of the limbs, and eventually most patients are wheelchair bound by the twenties. Cardiomyopathy with myocardial hypertrophy occurs very often and is the predominant cause of death. Type II diabetes, scoliosis, foot deformities, optic atrophy, and deafness are other relatively frequent symptoms.

Erythropoietin (EPO) is a glycoprotein that acts as a main regulator for erythropoiesis. Evidence suggests that both EPO and its receptor are expressed in the nervous tissue, and neuroprotective effects have been shown in animal models of cerebral ischemic damage. EPO increases frataxin levels in cultured human lymphocytes from FRDA patients. However, frataxin protein increase is not preceded by mRNA increase, suggesting that a post-transcriptional mechanism is involved. To date, four phase II clinical trials have been published regarding the use of EPO in FRDA patients.


Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Molecular diagnosis of Friedreich Ataxia
  • Age ≥12 years
  • Body weight ≥30, ≤90 Kg
  • SARA score ≤30
  • Patient able to read and sign the informed consent
  • Patients able to perform a cardiopulmonary test

Exclusion Criteria:

  • Treatment with Erythropoietin in the previous 12 months
  • Treatment with Idebenone
  • Contraindications to CPET: cardiac valve disease, ischemic cardiomyopathy, atrial fibrillation, asthma, chronic obstructive pulmonary disease, other arrhythmias judged as not compatible with exercise.
  • Any Cardiac and/or Hepatic and/or Renal disease judged as clinically relevant by the investigator
  • Any clinically relevant ECG abnormalities that may interfere with the study
  • Any abnormal and clinically relevant laboratory exams at screening visit that may interfere with the trial
  • Anemia with Hemoglobin <10 g/dL
  • Positive history for venous and/or arterial thrombosis
  • Drug-resistant arterial hypertension
  • Positive history for drug-resistant epilepsy
  • Patients in treatment with not allowed study drugs (starting from 3 months prior to screening)
  • Any acute/chronic disease that might interfere with the clinical trial, as judged by the investigator
  • Hypersensitivity to Epoetin alfa or any other component of the study drug
  • Patients not able to comply to the study
  • For female patients (Sexually not active, hysterectomized, sterilized, menopause patients are excluded from the following criteria): pregnancy and/or breastfeeding and/or inadequate contraception.
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Please refer to this study by its identifier: NCT01493973

Università di Bari
Bari, BA, Italy, 70124
Università la Sapienza, Neurologia C
Rome, RM, Italy, 00186
Dipartimento di Scienze Neurologiche
Napoli, Italy, 80131
Sponsors and Collaborators
Federico II University
Friedreich's Ataxia Research Alliance
Associazione Italiana per la lotta alle Sindromi Atassiche (AISA)
Study Director: Francesco Saccà, MD University Federico II, Naples Italy
  More Information

Additional Information:
Responsible Party: Alessandro Filla, Principal Investigator, Federico II University Identifier: NCT01493973     History of Changes
Other Study ID Numbers: FA_BBK_8
Study First Received: December 15, 2011
Last Updated: August 10, 2015

Keywords provided by Federico II University:
Epoetin alfa
VO2 max

Additional relevant MeSH terms:
Cerebellar Ataxia
Friedreich Ataxia
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
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
Epoetin Alfa
Hematinics processed this record on April 24, 2017