Efficacy Study of Epoetin Alfa in Friedreich Ataxia

NCT01493973 | Completed Phase 2 DMC

• 1 other identifier: FA_BBK_8
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 3

Brief 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. 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.

Conditions

Friedreich Ataxia

Keywords

Erythropoietin; EPO; Friedreich; Ataxia; Epoetin alfa; VO2 max; SARA; EQ-5D; frataxin

Outcome Measures

Primary Outcomes (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).

  48 weeks

Secondary Outcomes (7)

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

  24 and 48 weeks

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

  all timepoints

• Echocardiography

  24, and 48 weeks

• Vascular reactivity

  24 and 48 weeks

• Neurological progression

  24 and 48 weeks

Study Arms (2)

Epoetin alfa

EXPERIMENTAL

Patients will be treated with Epoetin alfa 1200 IU/Kg s.c. every 12 weeks

Drug: Epoetin alfa

Placebo

PLACEBO COMPARATOR

Placebo 1200 IU/Kg s.c. every 12 weeks

Drug: Placebo

Interventions

Epoetin alfa DRUG

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

Also known as: EPREX 40000 IU, EPREX 10000 IU

Epoetin alfa

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Federico II University: lead
• Friedreich's Ataxia Research Alliance: collaborator
• Associazione Italiana per la lotta alle Sindromi Atassiche (AISA): collaborator

Study Sites (3)

Università di Bari

Bari, BA, 70124, Italy

Location

Università la Sapienza, Neurologia C

Rome, RM, 00186, Italy

Location

Dipartimento di Scienze Neurologiche

Napoli, 80131, Italy

Location

Related Publications (5)

• 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.

  PMID: 21506154 BACKGROUND

• 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.

  PMID: 18581197 BACKGROUND

• 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.

  PMID: 18759345 BACKGROUND

• 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.

  PMID: 17702040 BACKGROUND

• 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.

  PMID: 16269021 BACKGROUND

Related Links

• Clinical trials site
• University Federico II, Naples Italy
• Friedreich Ataxia Research Alliance
• Associazione Italiana per la lotta alle Sindromi Atassiche

MeSH Terms

Conditions

Friedreich Ataxia; Ataxia

Interventions

Epoetin Alfa

Condition Hierarchy (Ancestors)

Spinocerebellar Degenerations; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Francesco Saccà, MD

  University Federico II, Naples Italy

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 15, 2011
• First Posted: December 16, 2011
• Study Start: January 1, 2013
• Primary Completion: October 1, 2014
• Study Completion: June 1, 2015
• Last Updated: August 11, 2015

Record last verified: 2015-08

Locations

IT (3)