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Interferon Gamma-1b in Friedreich Ataxia (FRDA)

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ClinicalTrials.gov Identifier: NCT01965327
Recruitment Status : Completed
First Posted : October 18, 2013
Results First Posted : April 30, 2015
Last Update Posted : April 13, 2021
Sponsor:
Collaborators:
Friedreich's Ataxia Research Alliance
Vidara Therapeutics Research Ltd
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

Tracking Information
First Submitted Date  ICMJE August 27, 2013
First Posted Date  ICMJE October 18, 2013
Results First Submitted Date  ICMJE April 15, 2015
Results First Posted Date  ICMJE April 30, 2015
Last Update Posted Date April 13, 2021
Study Start Date  ICMJE August 2013
Actual Primary Completion Date March 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 15, 2015)
Change in Whole Blood Frataxin Levels [ Time Frame: Frataxin levels were measured at the beginning and conclusion of treatment (baseline and 12 weeks) ]
Assessment of the change in whole blood frataxin levels as assessed by lateral flow assay using an immunoassay for frataxin. Frataxin levels in the blood were measured at each study visit. Change in frataxin level at the end of treatment (week 12) relative to frataxin level at baseline was analyzed.
Original Primary Outcome Measures  ICMJE
 (submitted: October 15, 2013)
Number of subjects with changes in Frataxin protein levels in Buccal cells and whole blood [ Time Frame: Day 0 (screening/baseline), 14, 28, 56, 84, 91, and 112 ]
Assess the effect of IFN-g on frataxin protein levels. This is will be done in parallel in buccal cells and whole blood in children with FRDA. Samples are assessed by lateral flow assay using an immuno assay for frataxin. Frataxin levels in blood and buccal cell will be measured at each study visit. Change in frataxin level relative to frataxin level at screening will be analyzed.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2015)
Change in Total Friedreich Ataxia Rating Scale (FARS) Score [ Time Frame: FARS score was calculated at the beginning and conclusion of treatment (baseline and 12 weeks) ]
The Friedreich Ataxia Rating Scale (FARS) is neurological rating scale specifically developed and validated for FRDA. The FARS includes assessments of stance, gait, upper and lower limb coordination, speech, proprioception and strength. In addition to the standard neurological examination, the FARS contains three quantitative performance measures and a component that assesses activities of daily living (ADL). Quantitative performance measures include the nine-hole peg test, and a timed 25-foot walk. FARS scores correlate significantly with functional disability, activities of daily living scores and disease duration. The scores from the three subscales are added to generate a total score ranging from 0 to 159, with a higher score indicating a greater level of disability.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 15, 2013)
  • number of participants with changes in Neurological outcomes [ Time Frame: Day 0 (Screening/Baseline), 28, 84, and 112 ]
    Assess the effect of IFN-g on neurological outcomes including neurologic exam (Friedreich ataxia rating scale), timed 25-foot walk, timed 9-hole pegboard test, vision testing (high and low contrast), and hearing testing in subjects with FRDA.
  • Number of participants with changes in Quality of Life [ Time Frame: Day 0 (screening/baseline), 14, 28, 56, 84, 91,and 112 ]
    Assess the effectiveness of IFN-g on quality of life in subjects with FRDA via a series of questionnaires. Questionnaires include an activities of daily living form, the modified fatigue impact scale, and the clinical global impression scale (performed by the PI and parents separately). In addition, parents and study subjects will complete a Pediatric Quality of Life questionnaire, which is age-specific.
  • Number of adverse events [ Time Frame: Day 14, 28, 56, 84, 91,and 112 ]
    Assess the safety and tolerability of IFN-g at the currently approved dose in the FRDA population. Number of adverse events, flu-like symptoms, and injection-site reactions will be assessed.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Interferon Gamma-1b in Friedreich Ataxia (FRDA)
Official Title  ICMJE Open-label Pilot Study of Interferon Gamma-1b (Actimmune™) for the Treatment of Friedreich Ataxia (FRDA)
Brief Summary Friedreich ataxia (FRDA) is a progressive neurodegenerative disease of children and adults for which there is presently no therapy. Recently, a study reported that interferon gamma (IFN-g) could raise frataxin protein levels in both cell lines derived from patients with Friedreich ataxia and in a mouse model with Friedreich ataxia. The present study will test whether IFN-g is safe, tolerated and potentially efficacious in a heterogeneous cohort of children with FRDA.
Detailed Description

Study Objectives:

Primary:

• To assess the effect of Interferon Gamma-1b (IFN-g) on increasing frataxin expression and protein in children with FRDA.

Secondary:

  • To assess the effect of IFN-g on neurological outcomes (FARS, performance measures, and hearing) in subjects with FRDA.
  • To assess the effectiveness of IFN-g on quality of life in subjects with FRDA.
  • To assess the safety and tolerability of IFN-g at the currently approved dose in the FRDA population.

Study Phases:

Screening - During screening, subjects will be assessed for inclusion and exclusion criteria.

Intervention - Subjects will begin treatment at baseline visit and the dose of study medication will be increased to the maximum dose over four weeks. The subjects will be maintained at the maximum dose for 8 weeks. After 12 weeks, treatment will stop. Study medication will be administered via subcutaneous injections three times per week for 12 weeks.

Follow-up - Follow-up visits will occur at 7 and 28 days after the subject has completed the 12 weeks of active treatment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Friedreich Ataxia
Intervention  ICMJE Drug: Interferon Gamma-1b

Subjects will begin by taking 10 mcg/m2 of IFN-g-1b for the first two weeks of the study. Dose will be escalated to 25 mcg/m2 of IFN-g-1b for weeks three and four of the study. Finally, the dose will be escalated to 50 mcg/m2 of IFN-g-1b for the last eight weeks of the study, which is the current dose approved by the FDA for children.

All doses will be administered via subcutaneous injection.

Other Names:
  • Actimmune™
  • IFN-g-1b
Study Arms  ICMJE Experimental: Interferon Gamma-1b (ACTIMMUNE)
All individuals in this study will be given active medication (interferon gamma-1b) for 12 weeks. This will be administered according to a dose-escalation schedule.
Intervention: Drug: Interferon Gamma-1b
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: October 15, 2013)
12
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 2014
Actual Primary Completion Date March 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects with FRDA confirmed by genetic testing with 2 expanded Guanine-adenine-adenine repeats
  • Females who are not pregnant or breast feeding, and who do not intend to become pregnant. Females of child-bearing potential must use a reliable method of contraception and must provide a negative urine pregnancy test at screening
  • Stable doses of all medications, vitamins and supplements for 30 days prior to study entry and for the duration of the study
  • Parent/guardian permission (informed consent) and child assent

Exclusion Criteria:

  • Any unstable illness that in the investigator's opinion precludes participation in this study
  • Use of any investigational product within 30 days prior to enrollment
  • Subjects with a history of substance abuse
  • Presence of clinically significant cardiac disease
  • History of hypersensitivity to IFN-g or E. coli derived products
  • Presence of severe renal disease or hepatic disease
  • Clinically significant abnormal White blood cell count, hemoglobin or platelet count
  • Any subject planning a scheduled surgical procedure during the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years to 17 Years   (Child)
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 NCT01965327
Other Study ID Numbers  ICMJE 13-010121
13-010121 ( Other Identifier: Children's Hospital of Philadelphia )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Hospital of Philadelphia
Study Sponsor  ICMJE Children's Hospital of Philadelphia
Collaborators  ICMJE
  • Friedreich's Ataxia Research Alliance
  • Vidara Therapeutics Research Ltd
Investigators  ICMJE
Principal Investigator: David Lynch, MD, PhD Children's Hospital of Philadelphia
PRS Account Children's Hospital of Philadelphia
Verification Date March 2021

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