Efficacy Study of Epoetin Alfa in Friedreich Ataxia (FRIEMAX)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Friedreich's Ataxia Research Alliance (FARA)
Associazione Italiana per la lotta alle Sindromi Atassiche (AISA)
Information provided by (Responsible Party):
Alessandro Filla, Federico II University
ClinicalTrials.gov Identifier:
NCT01493973
First received: December 15, 2011
Last updated: October 28, 2013
Last verified: October 2013

December 15, 2011
October 28, 2013
January 2013
September 2014   (final data collection date for primary outcome measure)
Peak oxygen uptake (VO2 max) at the cardiopulmonary exercise test (CPET) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
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).
Same as current
Complete list of historical versions of study NCT01493973 on ClinicalTrials.gov Archive Site
  • Secondary outcome variables at the CPET (anaerobic threshold, ventilatory efficiency, exercise duration, and power output). [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
  • Frataxin levels in peripheral blood mononuclear cells (PBMCs). [ Time Frame: all timepoints ] [ Designated as safety issue: No ]
  • Echocardiography [ Time Frame: 24, and 48 weeks ] [ Designated as safety issue: No ]
  • Vascular reactivity [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
    Vascular reactivity will be measured by the Flow-Mediated Dilation technique (FMD)
  • Neurological progression [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    Quality of life will be assessed with the EQ-5D, ADL, and IADL scales
  • Safety and tolerability [ Time Frame: all visits ] [ Designated as safety issue: Yes ]
    Safety and tolerability will be assessed by recording all serious and non serious adverse events at all visits of the trial
Same as current
Not Provided
Not Provided
 
Efficacy Study of Epoetin Alfa in Friedreich Ataxia
A Double-blind, Randomized, Placebo-controlled, Clinical Trial to Test the Efficacy of Epoetin Alfa on Physical Performance of Friedreich Ataxia Patients.

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Friedreich Ataxia
  • 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
  • Drug: Placebo
    Placebo
    Other Name: Placebo
  • Experimental: Epoetin alfa
    Patients will be treated with Epoetin alfa 1200 IU/Kg s.c. every 12 weeks
    Intervention: Drug: Epoetin alfa
  • Placebo Comparator: Placebo
    Placebo 1200 IU/Kg s.c. every 12 weeks
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
56
December 2014
September 2014   (final data collection date for primary outcome measure)

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.
Both
12 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Italy
 
NCT01493973
FA_BBK_8
Yes
Alessandro Filla, Federico II University
Federico II University
  • Friedreich's Ataxia Research Alliance (FARA)
  • Associazione Italiana per la lotta alle Sindromi Atassiche (AISA)
Study Director: Francesco Saccà, MD University Federico II, Naples Italy
Federico II University
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP