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Trial record 1 of 1 for:    NCT02415127
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Safety, Tolerability and Efficacy of ACTIMMUNE® Dose Escalation in Friedreich's Ataxia (STEADFAST)

This study has been completed.
Sponsor:
Collaborator:
Friedreich's Ataxia Research Alliance
Information provided by (Responsible Party):
Horizon Pharma Ireland, Ltd., Dublin Ireland
ClinicalTrials.gov Identifier:
NCT02415127
First received: February 12, 2015
Last updated: December 19, 2016
Last verified: December 2016
  Purpose
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.

Condition Intervention Phase
Friedreich's Ataxia
Drug: Interferon γ-1b
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Horizon Pharma Ireland, Ltd., Dublin Ireland:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • Change from baseline in Activities of Daily Living [ Time Frame: Baseline, weeks 13 and 26 ]
    Nine areas of activities of daily living (ADL) will be evaluated. These areas include: (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 subject or caregiver strongly feels that a task falls between two scores. The maximum score is 36.

  • 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 ]

Other Outcome Measures:
  • Pharmacokinetic (PK) profile analysis of ACTIMMUNE [ Time Frame: Sparse PK sampling: Week 4, Week 13, and Week 26. Frequent PK sampling: Week 4 only. ]
    Approximately 40 patients will remain confined overnight at week 4 for serial blood collections at pre-dose (approximately 30-60 minutes prior to dosing), 1-1.5 hours, 3-4 hours, 5-6 hours, 8-10 hours, 12-15 hours, 16-18 hours, and 22-24 hours after study drug administration for the determination of maximum concentration (Cmax), time to Cmax (Tmax), and Area Under the Curve (AUC). All patients will contribute a single blood sample at weeks 13 and 26 for population PK analysis.


Enrollment: 92
Study Start Date: June 2015
Study Completion Date: November 2016
Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Drug: interferon γ-1b Drug: Interferon γ-1b
Approximately 45 subjects will receive subcutaneous (SC) doses of ACTIMMUNE® three times a week (TIW) for a total of 26 weeks. 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 subjects 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 AEs.
Other Name: ACTIMMUNE®
Placebo Comparator: Placebo Drug: Placebo
Approximately 45 subjects will receive subcutaneous (SC) doses of placebo three times a week (TIW) for a total of 26 weeks. The volume of placebo is planned to correspond with volume of study drug that would be given to the patient if the patient was randomized to the study drug arm.

Detailed Description:
Approximately 90 subjects who meet the study eligibility criteria will be randomized in a 1:1 ratio to receive SC doses of either ACTIMMUNE® TIW or matching placebo TIW for a total of 26 weeks; the study drug dose (or corresponding volume of placebo) is planned to be escalated on a weekly basis over the first four weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m² or equivalent volumes of placebo). The dose may be reduced, interrupted, or held based on tolerability.
  Eligibility

Ages Eligible for Study:   10 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02415127

Locations
United States, California
University of California, Los Angeles Neurology Clinic
Los Angeles, California, United States, 90038
United States, Florida
University of Florida - Clinical Research Center
Gainesville, Florida, United States, 32603
United States, Iowa
University of Iowa Children's Hospital
Iowa City, Iowa, United States, 52242
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Horizon Pharma Ireland, Ltd., Dublin Ireland
Friedreich's Ataxia Research Alliance
Investigators
Principal Investigator: David Lynch, MD, PhD Children's Hospital of Philadelphia
  More Information

Responsible Party: Horizon Pharma Ireland, Ltd., Dublin Ireland
ClinicalTrials.gov Identifier: NCT02415127     History of Changes
Other Study ID Numbers: HZNP-ACT-301
Study First Received: February 12, 2015
Last Updated: December 19, 2016

Keywords provided by Horizon Pharma Ireland, Ltd., Dublin Ireland:
Interferon gamma

Additional relevant MeSH terms:
Ataxia
Cerebellar Ataxia
Friedreich Ataxia
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Spinocerebellar Degenerations
Spinal Cord Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Mitochondrial Diseases
Metabolic Diseases
Interferons
Interferon-gamma
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on April 28, 2017