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

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ClinicalTrials.gov Identifier: NCT02415127
Recruitment Status : Completed
First Posted : April 14, 2015
Results First Posted : December 8, 2017
Last Update Posted : December 8, 2017
Sponsor:
Collaborator:
Friedreich's Ataxia Research Alliance
Information provided by (Responsible Party):
Horizon Pharma Ireland, Ltd., Dublin Ireland

Tracking Information
First Submitted Date  ICMJE February 12, 2015
First Posted Date  ICMJE April 14, 2015
Results First Submitted Date  ICMJE November 6, 2017
Results First Posted Date  ICMJE December 8, 2017
Last Update Posted Date December 8, 2017
Study Start Date  ICMJE June 2015
Actual Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 7, 2017)
Change From Baseline to Week 26 in the Friedreich's Ataxia Rating Scale (FARS)-mNeuro Score [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 8, 2015)
Change in neurological outcome measured by Friedreich's Ataxia Rating Scale (FARS) [ Time Frame: Baseline, Week 13, Week 26 ]
To evaluate the effect of ACTIMMUNE® versus placebo on the change from Baseline to Week 26 in neurological outcome as measured by FARS excluding the peripheral nervous system subscale score and the facial and tongue atrophy and fasciculations from the bulbar subscale score (FARS-mNeuro score).
Change History Complete list of historical versions of study NCT02415127 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2017)
  • Change From Baseline to Week 26 in Activities of Daily Living (ADL) Score [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 8, 2015)
  • The effect of ACTIMMUNE on the timed 25-foot-walk test (T25FW) [ Time Frame: Baseline, Week 13, Week 26 ]
    To evaluate the effect of ACTIMMUNE® versus placebo on change from Baseline to Week 26 in the T25FW.
  • The effect of ACTIMMUNE® on the responder rate [ Time Frame: Baseline, Week 13, Week 26 ]
    To evaluate the effect of ACTIMMUNE® versus placebo on the responder rate (≥3 point improvement in the FARS-mNeuro score from Baseline to Week 26).
  • The effect of ACTIMMUNE® on the neurological outcome measured by the total FARS score [ Time Frame: Baseline, Week 13, Week 26 ]
    To evaluate the effect of ACTIMMUNE® versus placebo on the change from Baseline to Week 26 in neurological outcome as measured by the total FARS score (FARStot).
  • The incidence of treatment emergent adverse events will be summarized by the treatment group [ Time Frame: Baseline, Week 4, Week 13, Week 26, Week 28 ]
  • The change from baseline to post-dose values will be summarized by the treatment group for clinical laboratory safety data and vital sign data [ Time Frame: Baseline, Week 4, Week 13, Week 26 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: April 8, 2015)
Pharmacokinetic profile analysis of ACTIMMUNE [ Time Frame: Week 4, Week 13, and Week 26 ]
PK profile will be characterized. Approximately 40 patients will remain confined overnight at week 4 for serial blood collections. All patients will contribute a single blood sample at weeks 13 and 26 for PK analysis.
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability and Efficacy of ACTIMMUNE® Dose Escalation in Friedreich's Ataxia
Official Title  ICMJE 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
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 Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Friedreich's Ataxia
Intervention  ICMJE
  • Drug: Interferon γ-1b
    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).
    Other Name: ACTIMMUNE®
  • Drug: Placebo
    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.
Study Arms  ICMJE
  • Experimental: Interferon γ-1b
    Approximately 45 participants will receive subcutaneous (SC) doses of ACTIMMUNE® 3 times a week (TIW) for a total of 26 weeks.
    Intervention: Drug: Interferon γ-1b
  • Placebo Comparator: Placebo
    Approximately 45 participants will receive SC doses of placebo TIW for a total of 26 weeks.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 18, 2016)
92
Original Estimated Enrollment  ICMJE
 (submitted: April 8, 2015)
90
Actual Study Completion Date  ICMJE November 2016
Actual Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 10 Years to 25 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02415127
Other Study ID Numbers  ICMJE HZNP-ACT-301
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Horizon Pharma Ireland, Ltd., Dublin Ireland
Study Sponsor  ICMJE Horizon Pharma Ireland, Ltd., Dublin Ireland
Collaborators  ICMJE Friedreich's Ataxia Research Alliance
Investigators  ICMJE
Principal Investigator: David Lynch, MD, PhD Children's Hospital of Philadelphia
PRS Account Horizon Pharma Ireland, Ltd., Dublin Ireland
Verification Date December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP