Clinical trial NCT06016946: Friedreich Ataxia Global Clinical Consortium UNIFIED Natural History Study
Official title: Friedreich Ataxia Global Clinical Consortium UNIFIED Natural History Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Friedreich Ataxia
Keywords: Rare Disease
Neuro-degenerative disease
Ataxia
Neurodegenerative Diseases
Neurologic Manifestations
Genetic Diseases, Inborn
Lead sponsor: Friedreich's Ataxia Research Alliance
Sponsor class: OTHER
First posted: 2023-08-30
Enrollment: 3000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will include current participants from the existing FA-COMS and EFACTS natural history studies as well as enroll new individuals with Friedreich ataxia (FA) and healthy controls.

Brief summary: This project is a global, multicenter, prospective, longitudinal, observational natural history study that can be used to understand the disease progression and support the development of safe and effective drugs and biological products for Friedreich ataxia.

Detailed description: The UNIFAI Study: Friedreich Ataxia Global Clinical Consortium UNIFIED Natural History Study is a global research study designed to provide a deep and evolving understanding of the natural history of this rare and debilitating genetic disorder as well as inform clinical trial design and implementation.

Friedreich's Ataxia is a rare, inherited, multi-system condition characterized by progressive neurological and cardiac symptoms. It is caused by mutations in the FXN (frataxin) gene.

The UNIFAI study is a multicenter, prospective, longitudinal, observational study, which means that all data about the natural disease course will be captured at study visits conducted annually according to a single protocol for all sites. This study will recruit participants with FA worldwide, to be assessed annually for up to 25 years. Study participation involves yearly study visits with data collected from medical records and history along with clinical outcome assessments including, neurological exams, timed walking tests, upper limb function measures, and patient-reported quality of life assessments, with the option for sites to collect additional ancillary measures related to speech, vision, fatigue, balance and cognition.

This global study is a harmonization of two well-established, long-standing natural history studies in FA that have provided a framework for further investigation of clinical measures that can quantitatively assess FA: FACOMS (US, Canada, Australia, New Zealand, and India) and EFACTS (European countries). These studies have been conducted in parallel with many similarities in study conduct. Uniting these two existing studies and groups of researchers gives greater power to data previously collected as well as future data. It also continues efforts to expand the network of clinical research centers specializing in FA called the FA-Global Clinical Consortium.

Due to advances in understanding the genetic and cellular dysfunction of FA that lead to symptoms observed in affected individuals, there has been significant growth in the discovery and development of therapeutic approaches, many currently being evaluated in clinical trials and a first approved treatment in the United States in 2023. The UNIFAI study aims to build upon this momentum by focusing on several key objectives.

UNIFAI will assess the natural history of FA by collecting data from diagnosed individuals of all ages and stages of disease progression. The data collected includes demographics, medical history, medications, neurological and functional assessments, cardiac examinations, laboratory studies, and health questionnaires. The study will assess and evaluate clinical outcomes in individuals with FA, such as disease progression, symptom severity, and overall quality of life, by various factors that might influence such outcomes such as genetic mutation, demographics (age, geography), co-existing conditions, medications, or treatments. By tracking outcomes over time, researchers aim to discern patterns, trends, and potential variations in subgroups or in the effectiveness of therapies or interventions across a diverse group of participants.

The UNIFAI study aims to play a pivotal role in identifying clinical milestones and changes in natural history over time as new treatments emerge. The study will monitor how these interventions alter the trajectory of the disease, potentially leading to the identification of crucial tipping points, disease landmarks, or stages where interventions can be most impactful. This study has the potential to significantly improve our understanding of FA and lead to more effective treatments and improved outcomes for those living with FA.

The study aims to inform clinical trial design and the development and validation of novel clinical outcome assessments and biomarkers that can be used in clinical trials. The UNIFAI study aims to capture data from a wide and diverse cohort of individuals with FA so that this dataset can be used to inform the selection of inclusion and exclusion criteria and power calculations for trial designs with specific clinical outcome measures.

Eligibility criteria: Inclusion Criteria:

1. Both males and females of any age
2. Individuals with Friedreich ataxia (FA): Participants that meet genetically confirmed diagnosis of Friedreich ataxia
3. Written informed consent provided

   1. Informed consent must be obtained for all participants
   2. For underage participants, they and the parent/ legally authorized representative have to sign the informed consent form, child assent (if applicable)
   3. Persons who are not legally competent require the informed consent of their legally authorized representative

   Exclusion Criteria:
4. Unable or unwilling to provide informed consent
5. Acute or ongoing medical or other conditions that would interfere with the conduct and assessments of the study
6. For any reason in the opinion of the investigator, participant would be unlikely or unable to comply with study protocol requirements.

Primary outcomes:
measure: Change in modified Friedreich Ataxia Rating Scale (mFARS) Score
timeFrame: Baseline, Year 1-25
measure: Change in Scale for the Assessment and Rating of Ataxia (SARA) Score
timeFrame: Baseline, Year 1-25
measure: Change in FA Activities of Daily Living (ADL) Score
timeFrame: Baseline, Year 1-25
measure: Change in Upright Stability (US) Score
timeFrame: Baseline, Year 1-25
Secondary outcomes:
measure: Change in 9-hole peg test mean time (seconds)
timeFrame: Baseline, Year 1-25
measure: Change in Timed walk (25-foot or 8-meter) mean time (seconds)
timeFrame: Baseline, Year 1-25
measure: Change in Speech analysis scores
timeFrame: Baseline, Year 1-25
measure: Change in Ataxia Instrumented Measures (AIMs)clinical severity score
timeFrame: Baseline, Year 1-25
measure: Change in Lower Contrast Letter Acuity test score
timeFrame: Baseline, Year 1-25
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Ataxia Center
state: California
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Gainesville
country: United States
facility: University of Florida - Neurology
state: Florida
city: Tampa
country: United States
facility: USF Ataxia Research Center
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital - Neurology
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa, Stead Family Children's Hospital
state: Iowa
city: Columbus
country: United States
facility: Ohio State University - Neurology
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Parkville
country: Australia
facility: Murdoch Childrens Research Institute
state: Victoria
city: Innsbruck
country: Austria
facility: Medical University Innsbruck, Department of Neurology
city: Bruxelles
country: Belgium
facility: Université Libre de Bruxelles, Hôpital Erasme, Dpt of Neurology
city: Campinas
country: Brazil
facility: University of Campinas
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre - Montreal Neurological Institute
state: Quebec
city: Montréal
country: Canada
facility: CHUM - Hopital Notre-Dame
state: Quebec
city: Praha
country: Czechia
facility: Motol University Hospital, Centre for Hereditary Ataxias
city: Paris
country: France
facility: Paris Brain Institute
city: Strasbourg
country: France
facility: Hôpital de Hautepierre, Service de Neurologie
city: Aachen
country: Germany
facility: University Hospital Aachen, Dept. of Neurology
city: Bonn
country: Germany
facility: Deutsches Zentrum Für Neurodegenerative Erkrankungen
city: Munich
country: Germany
facility: University of Munich, Dept. of Neurology, Friedrich-Baur-Institut
city: Tübingen
country: Germany
facility: University of Tübingen, Dept. of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research
city: Athens
country: Greece
facility: National and Kapodistrian University of Athens, Neurogenetics Unit
city: New Delhi
country: India
facility: All India Institute of Medical Sciences (AIIMS)
state: NCT
city: Dublin
country: Ireland
facility: Tallaght University Hospital, Department of Neurology
city: Conegliano
country: Italy
facility: Referente Clinico-Scientifico di Polo IRCCS "E. Medea"
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
city: Roma
country: Italy
facility: Bambino Gesù Children's Hospital, Department of Neurosciences
city: Nijmegen
country: Netherlands
facility: Stichting Radboud Universitair Medisch Centrum
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu, Servicio de Neurología
city: Madrid
country: Spain
facility: Hospital Universitario La Paz, Servicio de Neurologia
city: London
country: United Kingdom
facility: University College of London, Ataxia Centre, National Hospital for Neurology and Neurosurgery
Study officials:
affiliation: Children's Hospital of Philadelphia
name: David Lynch, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Aachen
name: Jorg B Schulz, Prof
role: PRINCIPAL_INVESTIGATOR
References: