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Friedreich AtaxiaPhase 2FRIEMAXNCT01493973

Efficacy Study of Epoetin Alfa in Friedreich Ataxia

A Phase 2 study testing Epoetin alfa in people with Friedreich Ataxia, run by Federico II University at 3 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Friedreich Ataxia
What is being tested?
Epoetin alfa
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
56 participants
Where
3 sitesItaly
Study dates
Jan 2013to Jun 2015
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 15Show fewer
  • 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.

Trial locations and contacts

3 sites in 1 country.

Italy3 sites

  • Università di Bari

    Bari, BA, 70124

  • Dipartimento di Scienze Neurologiche

    Naples, 80131

  • Università la Sapienza, Neurologia C

    Rome, RM, 00186

Other trials in Italy

About this study

Official title: 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.

Read the 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.

Being tested
Epoetin alfa, Placebo
Keywords
Erythropoietin, EPO, Friedreich, Ataxia, Epoetin alfa, VO2 max, SARA, EQ-5D, frataxin
Medical subject headings
Friedreich Ataxia, Ataxia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Epoetin alfaDrug

    Also called EPREX 40000 IU, EPREX 10000 IU

    Epoetin alfa will be administered s.c. at 1200 IU/Kg every 12 weeks

  • PlaceboDrug

    Placebo

Study groups in NCT01493973
Study groupRoleWhat they receive
Epoetin alfaExperimentalPatients will be treated with Epoetin alfa 1200 IU/Kg s.c. every 12 weeks
Receives: Drug: Epoetin alfa
PlaceboPlacebo comparatorPlacebo 1200 IU/Kg s.c. every 12 weeks
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Peak oxygen uptake (VO2 max) at the cardiopulmonary exercise test (CPET)

    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).

    Measured: 48 weeks

Secondary outcomes (7)

  1. Secondary outcome variables at the CPET (anaerobic threshold, ventilatory efficiency, exercise duration, and power output).

    Measured: 24 and 48 weeks

  2. Frataxin levels in peripheral blood mononuclear cells (PBMCs).

    Measured: all timepoints

  3. Echocardiography

    Measured: 24, and 48 weeks

  4. Vascular reactivity

    Vascular reactivity will be measured by the Flow-Mediated Dilation technique (FMD)

    Measured: 24 and 48 weeks

  5. Neurological progression

    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)

    Measured: 24 and 48 weeks

  6. Quality of life

    Quality of life will be assessed with the EQ-5D, ADL, and IADL scales

    Measured: 24 and 48 weeks

  7. Safety and tolerability

    Safety and tolerability will be assessed by recording all serious and non serious adverse events at all visits of the trial

    Measured: all visits

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Dec 2011 (estimated)
  2. Study startJan 2013
  3. Primary completionOct 2014
  4. Study completionJun 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01493973
Sponsor's protocol ID
FA_BBK_8
Acronym
FRIEMAX
Status last verified
Aug 2015
First submitted
15 Dec 2011
Last updated
11 Aug 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • Sacca F, Piro R, De Michele G, Acquaviva F, Antenora A, Carlomagno G, Cocozza S, Denaro A, Guacci A, Marsili A, Perrotta G, Puorro G, Cittadini A, Filla A. Epoetin alfa increases frataxin production in Friedreich's ataxia without affecting hematocrit. Mov Disord. 2011 Mar;26(4):739-42. doi: 10.1002/mds.23435. Epub 2010 Nov 10.

    PubMed 21506154

  • Acquaviva F, Castaldo I, Filla A, Giacchetti M, Marmolino D, Monticelli A, Pinelli M, Sacca F, Cocozza S. Recombinant human erythropoietin increases frataxin protein expression without increasing mRNA expression. Cerebellum. 2008;7(3):360-5. doi: 10.1007/s12311-008-0036-x.

    PubMed 18581197

  • Boesch S, Sturm B, Hering S, Scheiber-Mojdehkar B, Steinkellner H, Goldenberg H, Poewe W. Neurological effects of recombinant human erythropoietin in Friedreich's ataxia: a clinical pilot trial. Mov Disord. 2008 Oct 15;23(13):1940-4. doi: 10.1002/mds.22294.

    PubMed 18759345

  • Boesch S, Sturm B, Hering S, Goldenberg H, Poewe W, Scheiber-Mojdehkar B. Friedreich's ataxia: clinical pilot trial with recombinant human erythropoietin. Ann Neurol. 2007 Nov;62(5):521-4. doi: 10.1002/ana.21177.

    PubMed 17702040

  • Sturm B, Stupphann D, Kaun C, Boesch S, Schranzhofer M, Wojta J, Goldenberg H, Scheiber-Mojdehkar B. Recombinant human erythropoietin: effects on frataxin expression in vitro. Eur J Clin Invest. 2005 Nov;35(11):711-7. doi: 10.1111/j.1365-2362.2005.01568.x.

    PubMed 16269021

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Epoetin alfa in people with Friedreich Ataxia, run by Federico II University at 3 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Peak oxygen uptake (VO2 max) at the cardiopulmonary exercise test (CPET) (time frame: 48 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01493973, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2015.

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