Clinical trials for adrenoleukodystrophy

Find the latest information related to clinical trials for adrenoleukodystrophy and adrenomyeloneuropathy in this section.

Status

  • Authorized in France and Spain
  • On-going patient recruitment in France and Spain
  • Awaiting authorization in Germany

Drug: MD1003 (biotin)
Objectives

  • To show clinical efficacy of the MD1003 treatment in AMN compared to placebo
  • To evaluate the safety of the treatment

Duration of the trial: 2 years
Start date: November 2014
Estimated end of the trial: April 2017

Principal investigator: Pr Patrick Aubourg, Bicetre hospital, Le Kremlin-Bicetre, France
Investigators

  • Pr Patrick Aubourg, Bicetre hospital, Le Kremlin-Bicetre, France
  • Dr Yann Nadjar, Pitié-Salpêtrière hospital, Paris, France
  • Dr Aurora Pujol, IDIBELL, Duran i Reinals hospital, L’Hospitalet de Llobregat, Spain
  • Dr Carlos Casasnoves, IDIBELL, Duran i Reinals hospital, L’Hospitalet de Llobregat, Spain
  • Pr Wolfgang Köhler, Hubertusburg hosital, Wemsdorf, Germany

Locations

  • Bicetre hospital, Le Kremlin-Bicetre, France
  • Pitié-Salpêtrière hospital, Paris, France
  • Duran i Reinals hospital, L’Hospitalet de Llobregat, Spain
  • Hubertusburg hospital, Wermsdorf, Germany

Sponsor: MedDay Pharmaceuticals, France - http://medday-pharma.com/
Funding: ELA - 800.000 euros
Reference : EudraCT 2014-000698-38
Patients
60 AMN men divided into 2 groups the first year of the treatment as follows:

  • 20 patients treated with a placebo
  • 40 patients treated with the MD1003 drug

During the second year of the trial, all the patients will receive the MD1003 drug.

Experimental treatment
Oral daily intake of MD1003 capsules at a dose of 300 mg or of placebo

Inclusion criteria

  • 18 to 60 years old men
  • Confirmed ABCD1 gene mutation
  • Increased very long chain fatty acids in plasma
  • Clinical signs of AMN with walking impairment
  • Normal cerebral MRI or MRI showing abnormalities of AMN patients without cerebral involvement
  • Corticoid treatment if adrenal insufficiency

Exclusion criteria

  • IMRI showing abnormalities of AMN patients with cerebral involvement
  • Other progressive neurological disease than AMN
  • Unable to perform walking and balance tests
  • Patients with liver impairment, renal or cardiovascular disease or evolutive cancer
  • Intake of drugs for AMN including fampridine if initiated less than a month before inclusion
  • MRI contraindications
  • Participation to another clinical trial for ALD

Outcome measures
Principal outcome measure: Mean change observed during the 2 Minutes walking test prior and after the 12 months treatment.

Secondary outcome measures

  • TW25FW walking test measuring the time to walk 25 feet
  • Time to stand up and go
  • Euroqol ED-5D quality of life questionnaire
  • Qualiveen questionnaire on urinary function
  • Safety assessment of elevated dose of biotin

Exploratories studies will also be conducted in some centers like MRIs, nerve velocity conduction and muscular strength.

Additional information

Contacts
France
email : jf.dhainaut@ela-fondation.com

Spain
Telephone : +34 932 607 137
Fax: +34 932 607 414
email : contact@medday-pharma.com

Source : https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000698-38/ES

Status: Authorized; patient recruitment active (Boston site)
Drug: Lentiviral vector Lenti-D carrying the normal human ABCD1 gene
Objective: To evaluate the safety and efficacy of the treatment in childhood cerebral ALD

Start date of the study: August 2013
Estimated end of the trial: August 2018

Director of the study: Dr. Asif Paker, bluebird bio, Inc.
Principal investigators

  • Dr. David Williams, Boston Children's Hospital, Boston, MA, USA
  • Dr. Christine Duncan, Children's Hospital, Boston, MA, USA
  • Dr. Florian Eichler, Massachusetts General Hospital, Boston, MA, USA

Locations:

  • Boston Children Hospital / Massachussetts General Hospital, Boston, MA, USA
  • University of California, Los Angeles, California, USA
  • University of Minnesota, Minneapolis, Minnesota, USA

Funding: bluebird bio

Reference : ALD-102 study, Starbeam study, NCT01896102

Patients
Fifteen children suffering from the cerebral form of ALD at a pre-symptomatic stage

Experimental protocol

  • Collection of bone marrow stem cells from the patient blood and isolation of the CD34+ stem cells
  • Transfer of the gene into the CD34+ stem cells using the viral vector.
  • Myeloablative conditioning of the patient (destruction of the bone marrow).
  • Reinfusion of the corrected cells in the patient (autotransplant).

Inclusion criteria

  • Age: Up to 15 years old
  • Gender: Male
  • Active childhood cerebral adrenoleukodystrophy
  • Neurological function score ≤ 1

Exclusion criteria

  • Receipt of an allogeneic transplant or gene therapy.
  • Availability of a willing 10/10 matched sibling donor.
  • Use of statins, Lorenzo's oil or diets aiming at lowering very long chain fatty acids. Note : subjects must discontinue use of these medications at time of consent.
  • Impossibility to perform MRI studies.
  • Hematological, hepatic, renal, pulmonary or cardiac compromise.
  • Infections and other conditions.

Patient follow-up
Patients will be followed-up several years after their gene therapy treatment.

Additional information

  • Other centers will be opened in the future in the United States and in Europe. When new centers will be authorized, we will update the section «  Clinical trials » of our website.

 

Contacts

  • Tara O'Meara, bluebird bio, Inc. – Telephone : +1 617-797-2555, e-mail : clinicaltrials@bluebirdbio.com
    Colleen Dansereau, Boston Children's Hospital/Massachusetts General Hospital – Telephone : +1 617-919-7008, e-mail : Colleen.Dansereau@childrens.harvard.edu
  • Dr Ami J Shah - University of California, Los Angeles, California, USA - Telephone : +1 310-825-6708, e-mail: AJShah@mednet.ucla.edu
  • Dayna Terrazas  - University of California, Los Angeles, California, USA - Telephone : +1 310-825-6708, e-mail : drterrazas@mednet.ucla.edu
  • Dr Paul Orchard - University of Minnesota, Minneapolis, Minnesota, USA - Telephone : +1 612-626-2313, e-mail : orcha001@umn.edu
  • Patty Kleinke - University of Minnesota, Minneapolis, Minnesota, USA - Telephone :  +1 612-273-0857, e-mail: pkleink1@fairview.org

Source: http://clinicaltrials.gov/ct2/show/NCT01896102
http://www.starbeamstudy.com

Status: Authorized; Not yet open for recruitment
Objective: To evaluate the safety and efficacy of allogenic hematopoietic stem cell transplantation in patients with childhood cerebral ALD aged 17 or younger.

Start date of the study: November 2014
Estimated end of the trial: November 2018

Director of the study: Dr. Asif Paker, bluebird bio, Inc.
Funding: bluebird bio

Reference : ALD-103 study, NCT02204904

Patients
35 boys aged 17 or younger receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of Childhood Cerebral Adrenoleukodystrophy prospectively or partially prospective/retrospective.

Primary outcome measures

  • Mortality
  • Incidence of successful of engraftment
  • Kinetics of engraftment
  • Frequency and severity of adverse events

Inclusion criteria

  • Be male and aged 17 years and younger (i.e., <18 years of age) at the time of parental/guardian consent and, where appropriate, subject assent.
  • Have a confirmed diagnosis of Childhood Cerebral ALD
  • Be scheduled for allo-HSCT evaluation/procedure at a study site or have received allo-HSCT within a maximum of 12 months before study site activation.

Exclusion criteria

  • Previous treatment with a Gene therapy" class="glossy" title="Procedure involving the insertion of a normal gene into an organism in order to achieve a therapeutic objective. This gene (transgene) can be the normal version of a defective gene causing disease or a gene that produces a protein with any therapeutic action." >gene therapy product
  • Received allo-HSCT earlier than 12 months before study site activation

Contact

Source: http://clinicaltrials.gov/show/NCT02204904

Status: Active - Recruiting patients
Objective: To evaluate abnormalities of the brain and spinal cord by MRI in order to understand the mechanisms leading to the disability of women with adrenomyeloneuropathy and the effect of physical exercise.

Investigator: Kathleen Zackowski, Hugo W. Moser Research Institute at Kennedy Krieger Institute, Baltimore, MA, USA

Start date: May 2012
Location: Hugo W. Moser Research Institute at Kennedy Krieger Institute, Baltimore, MA, USA
Duration: 25 months
Funding: ELA
Reference: NCT01594853

Patients
30 women with adrenomyeloneuropathy

SourceClinicaltrials.gov

Status: Closed
Objective: To test the efficacy of a cocktail of antioxidants in AMN patients
Drugs: Cocktail of 2 antioxidants (Vitamin E, Lipoic Acid) + N-acetylcysteine (expectorant)

Principal investigators
Dr. Aurora Pujol, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
Dr. Carlos Casasnovas, Department of Neurology, University Hospital of Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain

Start date: September 2011
Location: Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain
Duration: 26 months
Funding: Spanish Ministry of Health, Hesperia Foundation, ELA.
Reference: NCT01495260

Patients
20 AMN men with locomotor impairment
Symptomatic female carriers

Treatment
Daily intake of the 3 drugs

Outcome measures

  • Oxidative stress markers
  • Clinical assessments at the beginning and end of the study

SourceClinicaltrials.gov

Preliminary results of the trial (page 3)

Until now, treatment for ALD relied on bone marrow transplantation, an limited approach given the scarcity of donors and the risk of serious complications. In this new approach, clinicians chose autotransplantation combined with Gene therapy" class="glossy" title="Procedure involving the insertion of a normal gene into an organism in order to achieve a therapeutic objective. This gene (transgene) can be the normal version of a defective gene causing disease or a gene that produces a protein with any therapeutic action." >gene therapy. Stem cells from the patient bone marrow were collected and corrected in the laboratory before being reinfused to the patient. Some of these cells will naturally head to the brain of the patient where they could have a corrective effect.

Technological innovation: a viral vector derived from an inactivated and modified AIDS virus was used to introduce the correct gene in bone marrow stem cells. A discovery that opens up treatment perspectives  for other types of leukodystrophy and that will benefit other more common diseases (sickle cell anemia, beta-thalassemia, multiple immunodeficiencies, hemophilia, Parkinson's ...).

Status: Closed
Drug: Lentiviral vector carrying the normal human ABCD1 gene
Objective: Evaluation of the safety and efficacy of the treatment

Principal investigators
Patrick Aubourg, Bicêtre Hospital, Paris, France
Alain Fisher, Necker Hospital, Paris, France
Marina Cavazzana-Calvo, Necker Hospital, Paris, France

Start date: Fall 2006
Location: Bicêtre Hospital / Necker Hospital
Funding: ELA, Inserm, AP-HP, Paris Descartes University, AFM

Patients
4 children suffering from cerebral form of the disease at a presymptomatic stage without compatible bone marrow donors and with a progressive cerebral demyelination and adrenal insufficiency.

Experimental treatment in 4 phases

  • Collection of bone marrow stem cells from the patient blood and isolation of the stem cells
  • Transfer of the gene into the stem cells using the lentiviral vector
  • Myeloablative conditioning of the patient (destruction of the bone marrow)
  • Reinfusion of the corrected cells in the patient (autotransplant).

Patient follow-up

Patients will be followed for several years after their gene therapy treatment.

The results regarding the first two children treated were published in the prestigious scientific journal Science. After 24 to 30 months of patient follow-up , 10 to 15% of the patients’ blood cells still express the ALD protein that was previously undetectable. The normal ABCD1 gene was expressed by these cells four to five times more than the mutated gene. Also, 20 to 24 months after transplant, VLCFA that normally accumulate during the disease were reduced by 38% in the patients' plasma. From a neurological point of view, the cerebral demyelinating lesions in these two children progressed 14 to 16 months after transplant but have remained stable since then. In addition, the demyelinating lesion observed in the auditory pathway of one patient was reversed.

The arrest of progressive cerebral demyelination in these two children treated by gene therapy represents a clinical outcome comparable to that achieved by allogeneic bone marrow transplantation in ALD patients.

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