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

Phase 3

Completed

• Conditions: Friedreich's Ataxia
• Interventions: Drug: Interferon γ-1b; Drug: Placebo

• Registration Number: NCT02415127
• Lead Sponsor: Amgen

Brief Summary

The purpose of this phase 3 randomized, multi-center, double-blind, placebo-controlled study is to evaluate the efficacy and safety of ACTIMMUNE® (interferon-γ 1b) in the treatment of Friedreich's Ataxia (FA) and to evaluate the pharmacokinetic (PK) characteristics of ACTIMMUNE® in FA patients.

Detailed Description

Study with completed results acquired from Horizon in 2024.

Study Timeline

• Study First Submitted: 2015-02-12
• Study First Submitted QC: 2015-04-08
• Study First Posted: 2015-04-14
• Study Start: 2015-06
• Primary Completion: 2016-11
• Study Completion: 2016-11
• Results First Submitted: 2017-11-06
• Results First Submitted QC: 2017-12-07
• Results First Posted: 2017-12-08
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-25
• Last Update Posted: 2024-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 92

Inclusion Criteria

• Written informed consent and child assent, if applicable.
• FA confirmed by genetic testing with two expanded guanine-adenine-adenine (GAA) repeats.
• FA functional stage of >1 to <5 and ability to walk 25 feet with or without an assistive device.
• Male or female subject between the ages of 10 and 25 years, inclusive.
• If female, the subject is not pregnant or lactating or intending to become pregnant during the study, or within 30 days after the last dose of study drug. Female subjects of child-bearing potential must have a negative serum pregnancy test result at Screening, a negative urine pregnancy test result at Baseline, and agree to use a reliable method of contraception throughout the study and for 30 days after the last dose of study drug.

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Exclusion Criteria

• Any unstable illness that in the investigator's opinion precludes participation in the study.
• Use of any investigational product within 30 days prior to randomization.
• A history of substance abuse.
• Presence of clinically significant cardiac disease (as determined by the investigator based on electrocardiogram [ECG] and echocardiogram results at Screening). Specifically, an ejection fraction of <40% or a prolonged QT interval (>50% of cycle duration) will result in exclusion. If the investigator notes any other clinically significant abnormalities on the ECG or echocardiogram, the subject may be eligible if they are provided clearance from a cardiologist.
• History of hypersensitivity to interferon (IFN)-ɣ or E. coli-derived products.
• Presence of moderate or severe renal disease (estimated creatinine clearance <50 mL/min) or hepatic disease (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] >2x the upper limit of normal) as evidenced by laboratory results at Screening.
• Clinically significant abnormal white blood cell count, hemoglobin, or platelet count as evidenced by laboratory test results at Screening.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Interferon γ-1b	Interferon γ-1b	Approximately 45 participants will receive subcutaneous (SC) doses of ACTIMMUNE® 3 times a week (TIW) for a total of 26 weeks.
Placebo	Placebo	Approximately 45 participants will receive SC doses of placebo TIW for a total of 26 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Week 26 in the Friedreich's Ataxia Rating Scale (FARS)-mNeuro Score	Baseline, Week 26	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to Week 26 in Total Friedreich Ataxia Rating Scale Score (FARStot)	Baseline, Week 26	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.
Change From Baseline to Week 26 in Activities of Daily Living (ADL) Score	Baseline, Week 26	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.
Change From Baseline at Week 26 in Timed 25-Foot Walk (T25FW)	Baseline, Week 26	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.
Number of FARS-mNeuro Responders and Non-Responders at Week 26	Week 26	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).

Trial Locations

Locations (4)

University of Iowa Children's Hospital; 🇺🇸 Iowa City, Iowa, United States

University of California, Los Angeles Neurology Clinic; 🇺🇸 Los Angeles, California, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Florida - Clinical Research Center; 🇺🇸 Gainesville, Florida, United States