Interferon Gamma-1b in Friedreich Ataxia (FRDA)

Phase 2

Completed

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Interferon Gamma-1b (ACTIMMUNE)	Interferon Gamma-1b	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.

Primary Outcome Measures

Name	Time	Method
Change in Whole Blood Frataxin Levels	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.

Secondary Outcome Measures

Name	Time	Method
Change in Total Friedreich Ataxia Rating Scale (FARS) Score	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.