Efficacy Study of Epoetin Alfa in Friedreich Ataxia (FRIEMAX)

August 10, 2015 updated by: Alessandro Filla, Federico II University

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

56

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Napoli, Italy, 80131
        • Dipartimento di Scienze Neurologiche
    • BA
      • Bari, BA, Italy, 70124
        • Universita Di Bari
    • RM
      • Rome, RM, Italy, 00186
        • Università la Sapienza, Neurologia C

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
48 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary outcome variables at the CPET (anaerobic threshold, ventilatory efficiency, exercise duration, and power output).
Time Frame: 24 and 48 weeks
24 and 48 weeks
Frataxin levels in peripheral blood mononuclear cells (PBMCs).
Time Frame: all timepoints
all timepoints
Echocardiography
Time Frame: 24, and 48 weeks
24, and 48 weeks
Vascular reactivity
Time Frame: 24 and 48 weeks
Vascular reactivity will be measured by the Flow-Mediated Dilation technique (FMD)
24 and 48 weeks
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)
24 and 48 weeks
Quality of life
Time Frame: 24 and 48 weeks
Quality of life will be assessed with the EQ-5D, ADL, and IADL scales
24 and 48 weeks
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
all visits

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federico II University

Collaborators

Friedreich's Ataxia Research Alliance
Associazione Italiana per la lotta alle Sindromi Atassiche (AISA)

Investigators

  • Study Director: Francesco Saccà, MD, University Federico II, Naples Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (ACTUAL)

October 1, 2014

Study Completion (ACTUAL)

June 1, 2015

Study Registration Dates

First Submitted

December 15, 2011

First Submitted That Met QC Criteria

December 15, 2011

First Posted (ESTIMATE)

December 16, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

August 11, 2015

Last Update Submitted That Met QC Criteria

August 10, 2015

Last Verified

August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FA_BBK_8

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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