Trial Outcomes & Findings for Neurology Measures in FA Children (NCT NCT03418740)

NCT ID: NCT03418740

Last Updated: 2025-01-16

Results Overview

The Friedreich Ataxia Rating Scale (FARS) measures neurological function in FA. It is a composite measure reflecting neural substrates with five-subscales (sections A to E), measuring bulbar function, upper limb coordination, lower limb coordination, peripheral nerves, and upright stability. The modified FARS (mFARS) shortens the bulbar subscale to 2 items and excludes the peripheral nerve subscale. Total scoring is a summation of subscales, with a maximum score of 93 points for mFARS and 125 for FARS. The mFARS score ranges for each subscale are: Bulbar: 0 - 5, Upper Limb: 0 - 36, Lower Limb: 0 - 16, Upright Stability: 0 - 36. The overall change in mFARS and its sub scores across 3 years was the outcome measure analyzed at 0, 1, 2, and 3 year visits. Each subsection has a minimum score of 0, indicating minimal effect for that component. Maximum values per section vary based on the tasks performed in each subsection; a higher score indicates greater dysfunction on that component.

• Recruitment status: COMPLETED
• Target enrollment: 108 participants
• Primary outcome timeframe: Baseline up to 36 Months
• Results posted on: 2025-01-16

Participant Flow

Overall, among 108 individuals enrolled, 19 were excluded from the analysis population for one or more reasons. These included missing mFARS data at baseline or follow-up, early disease stage, and inability to ambulate at baseline.

Participant milestones

Measure	FA Children The present study enrolled 108 children aged 6.7 to 18y with genetically confirmed FRDA (Friedreich Ataxia) between Oct 2017 and October 2019.
Overall Study STARTED	108
Overall Study Number of Participants in the Analysis Population	89
Overall Study COMPLETED	85
Overall Study NOT COMPLETED	23

Reasons for withdrawal

Measure	FA Children The present study enrolled 108 children aged 6.7 to 18y with genetically confirmed FRDA (Friedreich Ataxia) between Oct 2017 and October 2019.
Overall Study Lost to Follow-up	13
Overall Study Scheduling Issues	7
Overall Study Withdrawal by Subject	2
Overall Study Unable to Continue Consent	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	FACHILD n=89 Participants The population enrolled in this study was a young, severely affected cohort, indicated by high GAA1 repeat lengths and early ages of onset. It was a mixed early/typical FRDA population, suggesting a certain level of diversity despite tight pediatric enrollment criteria.
Age, Continuous	13.3 Years STANDARD_DEVIATION 2.8 • n=89 Participants
Sex: Female, Male Female	48 Participants n=89 Participants
Sex: Female, Male Male	41 Participants n=89 Participants
Region of Enrollment United States	89 participants n=89 Participants
mFARS Total (93)	37.8 units on a scale STANDARD_DEVIATION 11.7 • n=89 Participants
Upright Stability (FARS E, 36)	22.3 units on a scale STANDARD_DEVIATION 5.3 • n=89 Participants
Upper Limbs (FARS B, 36)	9.2 units on a scale STANDARD_DEVIATION 5.3 • n=89 Participants
Lower Limbs (FARS C, 16)	5.9 units on a scale STANDARD_DEVIATION 2.4 • n=89 Participants
Bulbar Function (FARS A, 5)	0.3 units on a scale STANDARD_DEVIATION 0.5 • n=89 Participants

PRIMARY outcome

Timeframe: Baseline up to 36 Months

Population: Among 108 individuals enrolled,19 were excluded from the analysis population for one or more concurrent reasons. These included missing mFARS data (baseline or follow-up, n = 6), early disease stage (n = 3, mFARS baseline values 1, 7, 12.3), and inability to ambulate at baseline (n = 13).

The Friedreich Ataxia Rating Scale (FARS) measures neurological function in FA. It is a composite measure reflecting neural substrates with five-subscales (sections A to E), measuring bulbar function, upper limb coordination, lower limb coordination, peripheral nerves, and upright stability. The modified FARS (mFARS) shortens the bulbar subscale to 2 items and excludes the peripheral nerve subscale.

Total scoring is a summation of subscales, with a maximum score of 93 points for mFARS and 125 for FARS. The mFARS score ranges for each subscale are: Bulbar: 0 - 5, Upper Limb: 0 - 36, Lower Limb: 0 - 16, Upright Stability: 0 - 36.

The overall change in mFARS and its sub scores across 3 years was the outcome measure analyzed at 0, 1, 2, and 3 year visits. Each subsection has a minimum score of 0, indicating minimal effect for that component. Maximum values per section vary based on the tasks performed in each subsection; a higher score indicates greater dysfunction on that component.

Outcome measures

Measure	FA Children n=89 Participants Children between the ages of 6 and 18 with genetically confirmed Friedreich's Ataxia
Change in mFARS (Modified Friedreich's Ataxia Rating Scale) Score mFARS 1Y	2.9 units on a scale Interval 1.6 to 4.2
Change in mFARS (Modified Friedreich's Ataxia Rating Scale) Score mFARS 2Y	4.9 units on a scale Interval 3.6 to 6.3
Change in mFARS (Modified Friedreich's Ataxia Rating Scale) Score mFARS 3Y	7.7 units on a scale Interval 6.4 to 9.0
Change in mFARS (Modified Friedreich's Ataxia Rating Scale) Score FARS E 1Y	2.2 units on a scale Interval 1.5 to 2.9
Change in mFARS (Modified Friedreich's Ataxia Rating Scale) Score FARS E 2Y	3.7 units on a scale Interval 3.0 to 4.5
Change in mFARS (Modified Friedreich's Ataxia Rating Scale) Score FARS E 3Y	5.5 units on a scale Interval 4.7 to 6.2
Change in mFARS (Modified Friedreich's Ataxia Rating Scale) Score FARS B 1Y	0.3 units on a scale Interval -0.4 to 1.1
Change in mFARS (Modified Friedreich's Ataxia Rating Scale) Score FARS B 2Y	0.3 units on a scale Interval -0.4 to 1.1
Change in mFARS (Modified Friedreich's Ataxia Rating Scale) Score FARS B 3Y	0.6 units on a scale Interval -0.1 to 1.3

SECONDARY outcome

Timeframe: Baseline up to 36 Months

Population: Walking tests were carried out in the order: T25FW (twice), 1MW (twice), 6MW, and TUG. The T25FW, was most consistently performed at Baseline. Number of participants analyzed decreased after baseline at year 1, 2, and 3 as subjects were unable to complete the test. Reasons for not performing a test were missed visits, and, if assessment was performed, devices used.

The timed 25-foot walk (T25FW) test examines gait speed. The participant walks the distance of 25 feet as fast and safe as possible. Participants may use assistive devices during this task. The T25FW test was analyzed at 0, 1, 2, and 3 year visits.

Outcome measures

Measure	FA Children n=51 Participants Children between the ages of 6 and 18 with genetically confirmed Friedreich's Ataxia
Change in Timed 25-Foot Walk (T25FW) Test T25FW 1Y	-0.2 seconds Interval -0.3 to -0.1
Change in Timed 25-Foot Walk (T25FW) Test T25FW 2Y	-0.4 seconds Interval -0.5 to -0.3
Change in Timed 25-Foot Walk (T25FW) Test T25FW 3Y	-0.5 seconds Interval -0.6 to -0.4

SECONDARY outcome

Timeframe: Baseline up to 36 Months

Population: The number of participants analyzed decreased after baseline at years 1, 2, and 3 as subjects were unable to complete the test. Reasons for not performing a test were missed visits or refusal to complete task.

This test examines finger dexterity and involves placing and removing nine pegs in a pegboard and then removing them in the quickest possible time. The 9HPT has high intra- and inter-rater reliability and is the most commonly used measure of upper limb function in FA. The 9HPT was analyzed at 0, 1, 2, and 3 year visits.

Outcome measures

Measure	FA Children n=61 Participants Children between the ages of 6 and 18 with genetically confirmed Friedreich's Ataxia
Change in 9-Hole Peg Test (9HPT) 9HPT 3Y	-0.3 seconds Interval -0.3 to -0.2
Change in 9-Hole Peg Test (9HPT) 9HPT 1Y	-0.1 seconds Interval -0.2 to -0.1
Change in 9-Hole Peg Test (9HPT) 9HPT 2Y	-0.2 seconds Interval -0.3 to -0.2

SECONDARY outcome

Timeframe: Baseline up to 36 Months

Population: The TUG was assessed last and was performed by a higher proportion of patients vs. the 6MW. As the difficulty of the tests increased the amount of missing data increased, consistent with the progressive nature of FRDA. The number of participants analyzed decreased after baseline at years 1, 2, and 3 as subjects were unable to complete the test. Possible reasons for not performing a test were collected as "fatigue", "refused", "unable" and "unable, unrelated to disease progression".

The Timed Up and Go (TUG) test is a timed measure during which the participant has to stand up from a chair, walk 3 meters, turn around, walk back, and sit down. The participant is asked to perform the task as fast and as safe as possible. The TUG is a norm-referenced measure that has established reliability for quickly assessing functional ambulatory mobility and dynamic balance in adults and children. The TUG test was analyzed at 0, 1, 2, and 3 year visits.

Outcome measures

Measure	FA Children n=28 Participants Children between the ages of 6 and 18 with genetically confirmed Friedreich's Ataxia
Change in Timed Up and Go (TUG) Test TUG*100 1Y	-1.4 seconds Interval -2.3 to -0.5
Change in Timed Up and Go (TUG) Test TUG*100 2Y	-3.6 seconds Interval -4.6 to -2.6
Change in Timed Up and Go (TUG) Test TUG*100 3Y	-4.9 seconds Interval -5.9 to -3.9

SECONDARY outcome

Timeframe: Baseline up to 36 Months

Population: The number of participants analyzed decreased after baseline at years 1 and 2 as subjects were unable to complete the test. Reasons for not performing a test were missed visits, and refusal to complete task.

The Berg Balance Scale (BBS) is a widely used assessment to determine a person's balance abilities. The BBS includes a 14-item scale with static and dynamic activities of varying difficulty. The overall change in BBS score across 3 years was analyzed at 0, 1, 2, and 3 year visits. Scoring is based on a summation of the 14 item tasks scored on a five-point scale, with a range of 0-4 for each task.

0 = lowest level of function 4 = highest level of function. Highest possible score = 56 A score of < 45 indicates a greater risk of falling.

Outcome measures

Measure	FA Children n=49 Participants Children between the ages of 6 and 18 with genetically confirmed Friedreich's Ataxia
Change in Berg Balance Scale (Full Length) (BBS) Score BBS 1Y	-6.5 units on a scale Interval -9.1 to -3.9
Change in Berg Balance Scale (Full Length) (BBS) Score BBS 2Y	-10.4 units on a scale Interval -13.0 to -7.7
Change in Berg Balance Scale (Full Length) (BBS) Score BBS 3Y	-15 units on a scale Interval -17.6 to -12.5

SECONDARY outcome

Timeframe: Baseline up to 36 Months

Population: The number of participants analyzed decreased after baseline at years 1, 2, and 3 as subjects were unable to complete the test. Reasons for not performing a test were missed visits, and refusal to complete task.

The Activities of Daily Living (ADL) assesses functional status as a measurement of the participant's ability to perform activities of daily living independently. The ADL comprises 9 questions, each question scored on a scale of 0 to 4, though participants may use increments of 0.5 if they feel they fall between two items. As with the mFARS, the total ADL score is comprised of a summation of each scored question. A minimum value of 0 on the ADL scale indicates self-evaluation of minimal effect for neurological disease components. A maximum score of 36 on the ADL indicates most severe self-evaluation of symptoms included on the survey. The overall change in ADL score across 3 years was analyzed at 0, 1, 2, and 3 year visits.

Outcome measures

Measure	FA Children n=70 Participants Children between the ages of 6 and 18 with genetically confirmed Friedreich's Ataxia
Change in FA-Activities of Daily Living Scale (ADL) Score ADL 1Y	0.1 units on a scale Interval -0.7 to 0.9
Change in FA-Activities of Daily Living Scale (ADL) Score ADL 2Y	1.9 units on a scale Interval 1.1 to 2.7
Change in FA-Activities of Daily Living Scale (ADL) Score ADL 3Y	3 units on a scale Interval 2.2 to 3.9

SECONDARY outcome

Timeframe: Baseline up to 36 Months

Population: Walking tests were carried out in the order: T25FW (twice), 1MW (twice), 6MW, and TUG. There was a notable increase in fatigue and refusals to complete the longer walking tests after the first trial of the 1MW, followed by the 6MW. As the difficulty of the tests increased the amount of missing data increased, consistent with the progressive nature of FRDA. Possible reasons for not performing a test were collected as "fatigue", "refused", "unable" and "unable, unrelated to disease progression".

The Timed 1-minute Walk (T1MW) and timed 6-minute Walk are quantitative mobility and leg function performance tests based on distance traveled in one minute and six minutes. The participant is directed to one end of a clearly marked course and is instructed to walk back and forth as quickly as possible for one minute. The task is then repeated for six minutes. The distance is calculated by measuring how far the participant travels along the marked course.

Outcome measures

Measure	FA Children n=33 Participants Children between the ages of 6 and 18 with genetically confirmed Friedreich's Ataxia
Change in 1-minute Walk (1MW) and 6-minute Walk (6MW) Tests 1MW 1Y	-11 meters Interval -15.7 to -6.2
Change in 1-minute Walk (1MW) and 6-minute Walk (6MW) Tests 1MW 2Y	-15.7 meters Interval -20.8 to -10.7
Change in 1-minute Walk (1MW) and 6-minute Walk (6MW) Tests 1MW 3Y	-23.1 meters Interval -28.0 to -18.1
Change in 1-minute Walk (1MW) and 6-minute Walk (6MW) Tests 6MW 1Y	-13.1 meters Interval -56.0 to 29.7
Change in 1-minute Walk (1MW) and 6-minute Walk (6MW) Tests 6MW 2Y	-65.8 meters Interval -120.3 to -11.4
Change in 1-minute Walk (1MW) and 6-minute Walk (6MW) Tests 6MW 3Y	-67.4 meters Interval -129.9 to -4.9

Adverse Events

FA Children

Serious events: 0 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. David Lynch

The Children's Hospital of Philadelphia

Phone: 215-590-2242

Email: lynchd@pennmedicine.upenn.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place