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

Primary Purpose

Friedreich's Ataxia

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Interferon γ-1b
Placebo
Sponsored by
Horizon Pharma Ireland, Ltd., Dublin Ireland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Friedreich's Ataxia focused on measuring Interferon gamma

Eligibility Criteria

10 Years - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

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.

Sites / Locations

  • University of California, Los Angeles Neurology Clinic
  • University of Florida - Clinical Research Center
  • University of Iowa Children's Hospital
  • Children's Hospital of Philadelphia

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Interferon γ-1b

Placebo

Arm Description

Approximately 45 participants will receive subcutaneous (SC) doses of ACTIMMUNE® 3 times a week (TIW) for a total of 26 weeks.

Approximately 45 participants will receive SC doses of placebo TIW for a total of 26 weeks.

Outcomes

Primary Outcome Measures

Change From Baseline to Week 26 in the Friedreich's Ataxia Rating Scale (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). A negative change from baseline is an improvement.

Secondary Outcome Measures

Change From Baseline to Week 26 in Activities of Daily Living (ADL) Score
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)
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
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).
Change From Baseline to Week 26 in Total Friedreich Ataxia Rating Scale Score (FARStot)
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.

Full Information

First Posted
February 12, 2015
Last Updated
December 7, 2017
Sponsor
Horizon Pharma Ireland, Ltd., Dublin Ireland
Collaborators
Friedreich's Ataxia Research Alliance
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1. Study Identification

Unique Protocol Identification Number
NCT02415127
Brief Title
Safety, Tolerability and Efficacy of ACTIMMUNE® Dose Escalation in Friedreich's Ataxia
Acronym
STEADFAST
Official Title
Randomized, Multicenter, Double-Blind, Placebo-Controlled, Efficacy, Safety, and Pharmacokinetic Study of ACTIMMUNE® (Interferon γ-1b) in Children and Young Adults With Friedreich's Ataxia
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
June 2015 (undefined)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
November 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Horizon Pharma Ireland, Ltd., Dublin Ireland
Collaborators
Friedreich's Ataxia Research Alliance

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Friedreich's Ataxia
Keywords
Interferon gamma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
92 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Interferon γ-1b
Arm Type
Experimental
Arm Description
Approximately 45 participants will receive subcutaneous (SC) doses of ACTIMMUNE® 3 times a week (TIW) for a total of 26 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Approximately 45 participants will receive SC doses of placebo TIW for a total of 26 weeks.
Intervention Type
Drug
Intervention Name(s)
Interferon γ-1b
Other Intervention Name(s)
ACTIMMUNE®
Intervention Description
The study drug dose is planned to be escalated on a weekly basis over the first 4 weeks of treatment (from 10 µg/m² to 25, 50, and 100 µg/m²). The dose may be reduced, interrupted, or held based on tolerability. By Week 13, all participants are to be on a stable tolerated dose of study drug in order to continue study participation; the dose may not be further increased after week 13, however, it may be reduced on a case-by-case basis to manage drug-related adverse events (AEs).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
The volume of placebo is planned to correspond with volume of study drug that would be given to the participant if the participant was randomized to the study drug arm.
Primary Outcome Measure Information:
Title
Change From Baseline to Week 26 in the Friedreich's Ataxia Rating Scale (FARS)-mNeuro Score
Description
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.
Time Frame
Baseline, Week 26
Secondary Outcome Measure Information:
Title
Change From Baseline to Week 26 in Activities of Daily Living (ADL) Score
Description
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.
Time Frame
Baseline, Week 26
Title
Change From Baseline at Week 26 in Timed 25-Foot Walk (T25FW)
Description
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.
Time Frame
Baseline, Week 26
Title
Number of FARS-mNeuro Responders and Non-Responders at Week 26
Description
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).
Time Frame
Week 26
Title
Change From Baseline to Week 26 in Total Friedreich Ataxia Rating Scale Score (FARStot)
Description
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.
Time Frame
Baseline, Week 26

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Lynch, MD, PhD
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, Los Angeles Neurology Clinic
City
Los Angeles
State/Province
California
ZIP/Postal Code
90038
Country
United States
Facility Name
University of Florida - Clinical Research Center
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32603
Country
United States
Facility Name
University of Iowa Children's Hospital
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

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

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