Trial Outcomes & Findings for Safety, Tolerability and Efficacy of ACTIMMUNE® Dose Escalation in Friedreich's Ataxia (NCT NCT02415127)

Last Updated: 2024-12-19

Results Overview

The FARS assessment includes neurological signs that specifically reflect neural substrates affected in FA. Based on a neurological examination, bulbar, upper limb, lower limb, peripheral nerve, and upright stability/gait functions were assessed. The FARS-mNeuro score excludes the peripheral nervous system subscale score and the facial and tongue atrophy and fasciculations from the bulbar subscale score. Scores range from 0 (normal) to 93 (most impairment). A negative change from baseline is an improvement.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

92 participants

Primary outcome timeframe

Baseline, Week 26

Results posted on

2024-12-19

Participant Flow

Participant milestones

Participant milestones
Measure	Interferon γ-1b Subcutaneous (SC) doses of ACTIMMUNE® 3 times a week (TIW) for a total of 26 weeks.	Placebo SC doses of placebo TIW for a total of 26 weeks.
Overall Study STARTED	47	45
Overall Study COMPLETED	46	45
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Interferon γ-1b Subcutaneous (SC) doses of ACTIMMUNE® 3 times a week (TIW) for a total of 26 weeks.	Placebo SC doses of placebo TIW for a total of 26 weeks.
Overall Study Adverse Event	1	0

Baseline Characteristics

Safety, Tolerability and Efficacy of ACTIMMUNE® Dose Escalation in Friedreich's Ataxia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Interferon γ-1b n=47 Participants SC doses of ACTIMMUNE® TIW for a total of 26 weeks.	Placebo n=45 Participants SC doses of placebo TIW for a total of 26 weeks.	Total n=92 Participants Total of all reporting groups
Age, Continuous	16.5 years STANDARD_DEVIATION 4.41 • n=5 Participants	16.1 years STANDARD_DEVIATION 3.75 • n=7 Participants	16.3 years STANDARD_DEVIATION 4.08 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	26 Participants n=7 Participants	52 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	19 Participants n=7 Participants	40 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 26

Population: Intent-to-Treat (ITT) Population: All randomized participants with a valid baseline (including Screening) and at least 1 valid post baseline measurement in the primary efficacy outcome (FARS-mNeuro) and at Week 26. A valid FARS-mNeuro score was defined as no missing values in the questionnaire.

Outcome measures

Outcome measures
Measure	Interferon γ-1b n=46 Participants SC doses of ACTIMMUNE® TIW for a total of 26 weeks.	Placebo n=44 Participants SC doses of placebo TIW for a total of 26 weeks.
Change From Baseline to Week 26 in the Friedreich's Ataxia Rating Scale (FARS)-mNeuro Score	-0.6 units on a scale Standard Deviation 4.61	-1.0 units on a scale Standard Deviation 4.41

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Population: All randomized participants with a valid baseline (including Screening) and at least 1 valid post baseline measurement in the primary efficacy outcome (FARS-mNeuro) and ADL data at Baseline and Week 26. A valid FARS-mNeuro score was defined as no missing values in the questionnaire.

Participants and/or their caregivers rated 9 areas of daily living skills (speech, swallowing, cutting food and handling utensils, dressing, personal hygiene, falling, walking, quality of sitting position, and bladder function) on a 5-point scale (0=normal, 4=greatest loss of function) with allowable increments of 0.5 if the participant or caregiver strongly felt that a task falls between 2 scores. ADL scores can range from 0 (normal) to 36 (greatest loss of function). A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Interferon γ-1b n=46 Participants SC doses of ACTIMMUNE® TIW for a total of 26 weeks.	Placebo n=45 Participants SC doses of placebo TIW for a total of 26 weeks.
Change From Baseline to Week 26 in Activities of Daily Living (ADL) Score	0.64 units on a scale Standard Deviation 2.938	0.01 units on a scale Standard Deviation 2.595

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Population: All randomized participants with a valid baseline (including Screening) and at least 1 valid post baseline measurement in the primary efficacy outcome (FARS-mNeuro), and T25FW data at Baseline and Week 26. A valid FARS-mNeuro score was defined as no missing values in the questionnaire.

The T25FW is a quantitative measure of lower extremity function. Participants are directed to 1 end of a clearly marked 25-foot course and instructed to walk 25 feet as quickly as possible, but safely. The task is immediately administered again by having the participant walk back the same distance, and the score for the test is the average of the 2 walks (after reciprocal transformation). Participants may use assistive devices when performing this task, with the same assistive device used at each assessment. A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Interferon γ-1b n=44 Participants SC doses of ACTIMMUNE® TIW for a total of 26 weeks.	Placebo n=42 Participants SC doses of placebo TIW for a total of 26 weeks.
Change From Baseline at Week 26 in Timed 25-Foot Walk (T25FW)	-0.006 1/seconds Standard Deviation 0.0247	-0.003 1/seconds Standard Deviation 0.0181

SECONDARY outcome

Timeframe: Week 26

Population: ITT Population: All randomized participants with a valid baseline (including Screening) and at least 1 valid post baseline measurement in the primary efficacy outcome (FARS-mNeuro) and data at Week 26. A valid FARS-mNeuro score was defined as no missing values in the questionnaire.

A participant was considered a responder if they had an improvement (decrease) of at least 3 points from Baseline at Week 26 for the FARS-mNeuro score. The FARS assessment includes neurological signs that specifically reflect neural substrates affected in FA. Based on a neurological examination, bulbar, upper limb, lower limb, peripheral nerve, and upright stability/gait functions were assessed. The FARS-mNeuro score excludes the peripheral nervous system subscale score and the facial and tongue atrophy and fasciculations from the bulbar subscale score. Scores range from 0 (normal) to 93 (most impairment).

Outcome measures

Outcome measures
Measure	Interferon γ-1b n=46 Participants SC doses of ACTIMMUNE® TIW for a total of 26 weeks.	Placebo n=44 Participants SC doses of placebo TIW for a total of 26 weeks.
Number of FARS-mNeuro Responders and Non-Responders at Week 26 Responder	14 Participants	16 Participants
Number of FARS-mNeuro Responders and Non-Responders at Week 26 Non-responder	32 Participants	28 Participants

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Population: All randomized participants with a valid baseline (including Screening) and at least 1 valid post baseline measurement in the primary efficacy outcome (FARS-mNeuro) and FARStot data at Baseline and Week 26. A valid FARS-mNeuro score was defined as no missing values in the questionnaire.

The FARS assessment includes neurological signs that specifically reflect neural substrates affected in FA. Based on a neurological examination, bulbar, upper limb, lower limb, peripheral nerve, and upright stability/gait functions are assessed. FARStot scores range from 0 (normal) to 125 (most impairment). A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Interferon γ-1b n=46 Participants SC doses of ACTIMMUNE® TIW for a total of 26 weeks.	Placebo n=44 Participants SC doses of placebo TIW for a total of 26 weeks.
Change From Baseline to Week 26 in Total Friedreich Ataxia Rating Scale Score (FARStot)	-0.2 units on a scale Standard Deviation 5.53	-0.6 units on a scale Standard Deviation 5.19

Adverse Events

Interferon γ-1b

Serious events: 1 serious events

Other events: 45 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Interferon γ-1b n=47 participants at risk SC doses of ACTIMMUNE® TIW for a total of 26 weeks.	Placebo n=45 participants at risk SC doses of placebo TIW for a total of 26 weeks.
General disorders Chest pain	2.1% 1/47 • Treatment emergent adverse events (TEAEs) are presented. Adverse events (AEs) occurring or worsening after the dose on Day 1 through the end of the study (Week 26) were considered TEAEs. Serious TEAEs were collected through 2 weeks after study discontinuation (Week 28).	0.00% 0/45 • Treatment emergent adverse events (TEAEs) are presented. Adverse events (AEs) occurring or worsening after the dose on Day 1 through the end of the study (Week 26) were considered TEAEs. Serious TEAEs were collected through 2 weeks after study discontinuation (Week 28).
Infections and infestations Pneumonia	2.1% 1/47 • Treatment emergent adverse events (TEAEs) are presented. Adverse events (AEs) occurring or worsening after the dose on Day 1 through the end of the study (Week 26) were considered TEAEs. Serious TEAEs were collected through 2 weeks after study discontinuation (Week 28).	2.2% 1/45 • Treatment emergent adverse events (TEAEs) are presented. Adverse events (AEs) occurring or worsening after the dose on Day 1 through the end of the study (Week 26) were considered TEAEs. Serious TEAEs were collected through 2 weeks after study discontinuation (Week 28).
Metabolism and nutrition disorders Dehydration	0.00% 0/47 • Treatment emergent adverse events (TEAEs) are presented. Adverse events (AEs) occurring or worsening after the dose on Day 1 through the end of the study (Week 26) were considered TEAEs. Serious TEAEs were collected through 2 weeks after study discontinuation (Week 28).	2.2% 1/45 • Treatment emergent adverse events (TEAEs) are presented. Adverse events (AEs) occurring or worsening after the dose on Day 1 through the end of the study (Week 26) were considered TEAEs. Serious TEAEs were collected through 2 weeks after study discontinuation (Week 28).

Other adverse events

Additional Information

Julie Ball, Executive Director Clinical Development & Operations

Horizon Pharma Ireland, Ltd. Dublin, Ireland

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Horizon requests that any Investigator/institution that plans on presenting or publishing results provide written notification of their request a minimum of 60 days prior to presentation or publication. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsors' Intellectual Property rights .
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