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

Tracking Information

• First Submitted Date: August 27, 2013
• First Posted Date: October 18, 2013
• Results First Submitted Date: April 15, 2015
• Results First Posted Date: April 30, 2015
• Last Update Posted Date: April 13, 2021
• Study Start Date: August 2013
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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.

Current Secondary Outcome Measures (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 (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: Interferon Gamma-1b in Friedreich Ataxia (FRDA)
• 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 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
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Friedreich Ataxia

Intervention

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

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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 15, 2013): 12
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 2014
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 5 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01965327
• Other Study ID Numbers: 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: Not Provided
• Current Responsible Party: Children's Hospital of Philadelphia
• Original Responsible Party: Same as current
• Current Study Sponsor: Children's Hospital of Philadelphia
• Original Study Sponsor: Same as current

Collaborators

• Friedreich's Ataxia Research Alliance
• Vidara Therapeutics Research Ltd

Investigators

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

• PRS Account: Children's Hospital of Philadelphia
• Verification Date: March 2021