Interferon Gamma-1b in Friedreich Ataxia (FRDA)

• 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: Children's Hospital of Philadelphia
• Collaborators: Friedreich's Ataxia Research Alliance; Vidara Therapeutics Research Ltd
• Information provided by (Responsible Party): Children's Hospital of Philadelphia

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Friedreich Ataxia	Drug: Interferon Gamma-1b	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-label Pilot Study of Interferon Gamma-1b (Actimmune™) for the Treatment of Friedreich Ataxia (FRDA)
• Study Start Date: August 2013
• Actual Primary Completion Date: March 2014
• Actual Study Completion Date: October 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Children's Hospital of Philadelphia

Friedreich's Ataxia Research Alliance

Vidara Therapeutics Research Ltd

Investigators

• Principal Investigator: David Lynch, MD, PhD; Children's Hospital of Philadelphia

More Information

• Responsible Party: Children's Hospital of Philadelphia
• ClinicalTrials.gov Identifier: NCT01965327
• Other Study ID Numbers: 13-010121; 13-010121 ( Other Identifier: Children's Hospital of Philadelphia )
• First Posted: October 18, 2013
• Results First Posted: April 30, 2015
• Last Update Posted: April 13, 2021
• Last Verified: March 2021

Keywords provided by Children's Hospital of Philadelphia:

Friedreich ataxia; Interferon gamma-1b; FRDA

Additional relevant MeSH terms:

Ataxia; Cerebellar Ataxia; Friedreich Ataxia; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Mitochondrial Diseases; Metabolic Diseases; Interferons; Interferon-gamma; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents