- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02415127
Safety, Tolerability and Efficacy of ACTIMMUNE® Dose Escalation in Friedreich's Ataxia (STEADFAST)
December 7, 2017 updated by: Horizon Pharma Ireland, Ltd., Dublin Ireland
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
92
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
California
-
Los Angeles, California, United States, 90038
- University of California, Los Angeles Neurology Clinic
-
-
Florida
-
Gainesville, Florida, United States, 32603
- University of Florida - Clinical Research Center
-
-
Iowa
-
Iowa City, Iowa, United States, 52242
- University of Iowa Children's Hospital
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104
- Children's Hospital of Philadelphia
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
10 years to 25 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
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 Names:
|
Placebo Comparator: Placebo
Approximately 45 participants will receive SC doses of placebo 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 participant if the participant was randomized to the study drug arm.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline, Week 26
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline, Week 26
|
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.
|
Baseline, Week 26
|
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).
|
Week 26
|
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.
|
Baseline, Week 26
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: David Lynch, MD, PhD, Children's Hospital of Philadelphia
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2015
Primary Completion (Actual)
November 1, 2016
Study Completion (Actual)
November 1, 2016
Study Registration Dates
First Submitted
February 12, 2015
First Submitted That Met QC Criteria
April 8, 2015
First Posted (Estimate)
April 14, 2015
Study Record Updates
Last Update Posted (Actual)
December 8, 2017
Last Update Submitted That Met QC Criteria
December 7, 2017
Last Verified
December 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Genetic Diseases, Inborn
- Neurodegenerative Diseases
- Dyskinesias
- Spinal Cord Diseases
- Heredodegenerative Disorders, Nervous System
- Mitochondrial Diseases
- Cerebellar Diseases
- Spinocerebellar Degenerations
- Ataxia
- Cerebellar Ataxia
- Friedreich Ataxia
- Anti-Infective Agents
- Antiviral Agents
- Antineoplastic Agents
- Interferons
- Interferon-gamma
Other Study ID Numbers
- HZNP-ACT-301
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Friedreich's Ataxia
-
University of ChicagoPfizer; Biogen; APDM Wearable TechnologiesActive, not recruitingSpinocerebellar Ataxia Type 3 | Friedreich Ataxia | Spinocerebellar Ataxia Type 1 | Spinocerebellar Ataxia Type 2 | Spinocerebellar Ataxia Type 6United States
-
University of South FloridaCompletedFriedreich's Ataxia | Spinocerebellar Ataxia - All Sub-typesUnited States
-
Institut National de la Santé Et de la Recherche...Not yet recruiting
-
PTC TherapeuticsActive, not recruitingFriedreich AtaxiaUnited States
-
PTC TherapeuticsCompletedFriedreich AtaxiaUnited States, Australia, Brazil, Canada, France, Germany, Italy, New Zealand, Spain
-
PTC TherapeuticsEnrolling by invitationFriedreich AtaxiaUnited States, Australia, Brazil, Canada, France, Germany, Italy, New Zealand, Spain
-
Children's Hospital of PhiladelphiaFriedreich's Ataxia Research Alliance; Stealth BioTherapeutics Inc.Active, not recruitingFriedreich AtaxiaUnited States
-
Metro International Biotech, LLCChildren's Hospital of PhiladelphiaCompleted
-
Santhera PharmaceuticalsCompletedFriedreich's AtaxiaUnited States
-
Design TherapeuticsCompleted
Clinical Trials on Interferon γ-1b
-
Horizon Pharma Ireland, Ltd., Dublin IrelandFriedreich's Ataxia Research AllianceCompletedFriedreich's AtaxiaUnited States
-
Horizon Pharma Ireland, Ltd., Dublin IrelandFriedreich's Ataxia Research AllianceCompletedFriedreich's AtaxiaUnited States
-
Huntington Medical Research InstitutesInterMuneUnknown
-
Sawa Ito, MDHorizon Pharma USA, Inc.CompletedMyelodysplastic Syndromes | Myeloid Leukemia | Allogeneic Stem Cell TransplantationUnited States
-
S. Andrea HospitalItalian Multiple Sclerosis FoundationCompleted
-
National Cancer Institute (NCI)CompletedRecurrent Mycosis Fungoides and Sezary Syndrome | Refractory Mycosis Fungoides and Sezary Syndrome | Stage IB Mycosis Fungoides and Sezary Syndrome AJCC v7 | Stage IIA Mycosis Fungoides and Sezary Syndrome AJCC v7 | Stage IIB Mycosis Fungoides and Sezary Syndrome AJCC v7 | Stage IIIA Mycosis... and other conditionsUnited States
-
Nantes University HospitalActive, not recruiting
-
The Cleveland ClinicNational Cancer Institute (NCI)CompletedMelanoma | Sarcoma | Lymphoma | Kidney Cancer | Breast Cancer | Multiple Myeloma | Unspecified Adult Solid Tumor, Protocol SpecificUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)CompletedKidney CancerUnited States
-
Children's Hospital of PhiladelphiaFriedreich's Ataxia Research Alliance; Vidara Therapeutics Research LtdCompleted