Interferon Gamma-1b in Friedreich Ataxia (FRDA)

Open-label Pilot Study of Interferon Gamma-1b (Actimmune™) for the Treatment of Friedreich Ataxia (FRDA)

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.

Study Overview

• Status: Completed
• Conditions: Friedreich Ataxia
• Intervention / Treatment: Drug: Interferon Gamma-1b

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: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Whole Blood Frataxin Levels	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.	Frataxin levels were measured at the beginning and conclusion of treatment (baseline and 12 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total Friedreich Ataxia Rating Scale (FARS) Score	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.	FARS score was calculated at the beginning and conclusion of treatment (baseline and 12 weeks)

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: Friedreich's Ataxia Research Alliance; Vidara Therapeutics Research Ltd
• Investigators: Principal Investigator: David Lynch, MD, PhD, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: August 27, 2013
• First Submitted That Met QC Criteria: October 15, 2013
• First Posted (Estimate): October 18, 2013

Study Record Updates

• Last Update Posted (Actual): April 13, 2021
• Last Update Submitted That Met QC Criteria: March 23, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: FRDA; Friedreich ataxia; Interferon gamma-1b
• 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: 13-010121 (Other Identifier: Children's Hospital of Philadelphia)