Clinical Trial: Interferon Gamma-1b in Friedreich Ataxia (FRDA)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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 Summary:

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.


Sponsor: Children's Hospital of Philadelphia

Current Primary Outcome: 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: 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.


Current Secondary Outcome: 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:

  • 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.


Information By: Children's Hospital of Philadelphia

Dates:
Date Received: August 27, 2013
Date Started: August 2013
Date Completion:
Last Updated: April 29, 2015
Last Verified: April 2015