Understanding the Natural History Early in the Course or Presentation of Friedreich Ataxia (EARLY-FA)

Understanding the Natural History Early in the Course or Presentation of Friedreich Ataxia (EARLY-FA); Evaluating New Clinical Outcome Assessments in Children With Friedreich Ataxia to Facilitate Clinical Trial Design.

Multicenter, prospective, observational natural history and outcome measure study of children and young adults with Friedreich ataxia.

Study Overview

• Status: Withdrawn
• Conditions: Rare Diseases; Friedreich Ataxia
• Intervention / Treatment: Other: Geneticlly confirmed disease causing FXN mutatuion; Other: Healthy Control

Detailed Description

A multicenter, prospective, observational natural history and outcome measure study of children and young adults with Friedreich ataxia to further understand the disease features and progression and inform and enable future clinical trials in children with FA.

The study, Understanding the natural history early in the presentation of Friedreich ataxia: evaluating new clinical outcome assessments in children with Friedreich ataxia to facilitate clinical trial design (EARLY-FA), evaluates disease features specific to children and novel biomarkers and outcome measures which leveraging existing clinical research infrastructure and data collection from an established natural history study, UNIFAI.

• Study Type: Observational

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Murdoch Childrens Research Institute
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H9R 2Y2
      • McGill University Health Centre - Montreal Neurological Institute
• Germany
  • Aachen, Germany, 52074
    • University Hospital Aachen, Dept. of Neurology
• Italy
  • Roma, Italy, 00146
    • Bambino Gesù Children's Hospital, Department of Neurosciences
• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa, Stead Family Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study will enroll 200 individuals with FA who are 4-21 years of age and 100 healthy matched (age and sex) controls.

Description

Inclusion criteria for participants with FA:

1. Genetic diagnosis of Friedreich Ataxia
2. Ages 4-21 years at enrollment
3. Enrollment in the UNIFAI study and ability to have simultaneous visits for both UNIFAI and EARLY-FA

4. Informed consent must be obtained for all participants:

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

Inclusion criteria for control participants:

1. Ages 4-21 years at enrollment
2. Matching criteria to an enrolled participant with FA (age, sex and educational status)

3. Informed consent must be obtained for all participants:

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

Exclusion criteria for participants with FA:

1. Diagnosis of non-FA medical or other condition that in the opinion of the investigator would interfere with the conduct and assessments of the study or be confounding and contraindication to participation.
2. Pregnant female participants
3. Unable to provide informed consent.

Exclusion criteria for control participants:

1. Family risk for FA with unknown status
2. Diagnosis of a medical condition that in the opinion of the investigator could be confounding and contraindication to participation
3. Unable to provide informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
FRDA, genetically confirmed; individuals with FRDA, genetically confirmed, aged 4-21yrs	Other: Geneticlly confirmed disease causing FXN mutatuion; No intervention in this observational Natural History Study
Matched healthy controls; Participants in the control group (Group 2) will be aged 4-21 years at enrollment and fulfill group matching criteria to an enrolled participant with FRDA (age, sex)	Other: Healthy Control; No intervention in this observational Natural History Study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between growth (height in z-score) and disease severity in FRDA (mFARS score)	Height (cm) will be measured using a wall-mounted stadiometer and univariate analyses will test for Correlation between the height Z-score (after accounting for genetic potential (mid-parental height)) and disease severity (using the standard ataxia scale modified Friedreichs ataxia rating scale (mFARS)). The modified Friedreich Ataxia Rating Scale (mFARS) is a disease-specific scale that measures progression of neurological effects of FA. The mFARS is a validated and reliable scale; comprised of the neurologic component of the FARS and evaluates bulbar, upper limb, lower limb, and upright stability/gait function. For each item, responses categorize the corresponding neurological finding, and the findings are assigned a score ranging from 0 to 3, 4, or 5 with 0 being normal and higher numbers indicative of greater impairment. The score ranges from 0 to 93. The score will be compared to the previous year annually for up to 25 years.	Baseline, 12 months, and 24 months

Collaborators and Investigators

• Sponsor: Friedreich's Ataxia Research Alliance
• Investigators: Study Director: Jennifer Farmer, Friedreich's Ataxia Research Alliance

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: August 15, 2024
• First Submitted That Met QC Criteria: August 15, 2024
• First Posted (Actual): August 19, 2024

Study Record Updates

• Last Update Posted (Actual): June 8, 2025
• Last Update Submitted That Met QC Criteria: June 4, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Disease Attributes; Genetic Diseases, Inborn; Metabolic Diseases; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Spinal Cord Diseases; Dyskinesias; Mitochondrial Diseases; Cerebellar Diseases; Spinocerebellar Degenerations; Rare Diseases; Ataxia; Cerebellar Ataxia; Friedreich Ataxia
• Other Study ID Numbers: 2024-025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

All such study data will be made available to all study investigators after it has been generated, per the policies outlined in the study agreements and for analysis. The sponsor plans to make de-identified data available to third parties at the conclusion of the study and after primary manuscripts have been published, including depositing data in a secure platform.

All de-identified dataset(s) that can be shared will be deposited in the Rare Disease Cures Accelerator Data and Analytics Platform (RDCA-DAP) hosted and managed by the Critical Path Institute (C-Path). RDCA-DAP is an FDA-funded initiative that provides a centralized and standardized infrastructure to support and accelerate rare disease characterization with the goal of accelerating therapy development.

Each site will be required to ensure that participants are consented in such a way that allows the sharing of de-identified data with the community in this manner.

• IPD Sharing Time Frame: At the conclusion of the study and after primary manuscripts have been published
• IPD Sharing Access Criteria: Access and requests managed by the RDCA DAP platform
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No