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 Type: Interventional
• 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
• Enrollment: 12

Participant Flow

Recruitment Details	12 subjects were screened and all were enrolled in the study between September - December 2013.
Pre-assignment Details

Arm/Group Title	Interferon Gamma-1b (ACTIMMUNE)
Arm/Group Description	All individuals in this study were treated with interferon gamma-1b (ACTIMMUNE). Doses were administered via subcutaneous injections three times per week for 12 weeks. Dose-escalation schedule was completed by all subjects as follows: For the first two weeks subjects took10 mcg/m2 of interferon gamma-1b (IFN-g-1b), then the dose was escalated to 25 mcg/m2 of IFN-g-1b for weeks three and four of the study, finally, the dose was escalated to 50 mcg/m2 of IFN-gamma-1b for the last eight weeks of the study, which is the current dose approved by the FDA for children.
Period Title: Overall Study
Started	12
Completed	10 [1]
Not Completed	2
Reason Not Completed
Physician Decision	2
[1] Prior to completion, 2 subjects were withdrawn by the PI for failure to adhere to study protocol.

Baseline Characteristics

Arm/Group Title		Interferon Gamma-1b (ACTIMMUNE)
Arm/Group Description		All individuals in this study were treated with interferon gamma-1b (ACTIMMUNE). Doses were administered via subcutaneous injections three times per week for 12 weeks. Dose-escalation schedule was completed by all subjects as follows: For the first two weeks subjects took10 mcg/m2 of interferon gamma-1b (IFN-g-1b), then the dose was escalated to 25 mcg/m2 of IFN-g-1b for weeks three and four of the study, finally, the dose was escalated to 50 mcg/m2 of IFN-gamma-1b for the last eight weeks of the study, which is the current dose approved by the FDA for children.
Overall Number of Baseline Participants		12
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants
	<=18 years	12 100.0%
	Between 18 and 65 years	0 0.0%
	>=65 years	0 0.0%
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	12 participants
		12; (8 to 17)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants
	Female	3 25.0%
	Male	9 75.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants
	Hispanic or Latino	0 0.0%
	Not Hispanic or Latino	12 100.0%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants
	American Indian or Alaska Native	0 0.0%
	Asian	1 8.3%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	11 91.7%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	12 participants
		12

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The primary analysis was based on an intent-to-treat approach including all subjects who had baseline frataxin blood levels collected.

Arm/Group Title	Interferon Gamma-1b (ACTIMMUNE)
Arm/Group Description:	All individuals in this study were treated with interferon gamma-1b (ACTIMMUNE). Doses were administered via subcutaneous injections three times per week for 12 weeks. Dose-escalation schedule was completed by all subjects as follows: For the first two weeks subjects took10 mcg/m2 of interferon gamma-1b (IFN-g-1b), then the dose was escalated to 25 mcg/m2 of IFN-g-1b for weeks three and four of the study, finally, the dose was escalated to 50 mcg/m2 of IFN-gamma-1b for the last eight weeks of the study, which is the current dose approved by the FDA for children.
Overall Number of Participants Analyzed	12
Mean (Standard Deviation); Unit of Measure: percentage of baseline frataxin level
	-1.5 (1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Interferon Gamma-1b (ACTIMMUNE)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.027
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	Missing data were imputed by last observation carried forward.

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis was based on an intent-to-treat approach and included all subjects with baseline FARS assessment.

Arm/Group Title	Interferon Gamma-1b (ACTIMMUNE)
Arm/Group Description:	All individuals in this study were treated with interferon gamma-1b (ACTIMMUNE). Doses were administered via subcutaneous injections three times per week for 12 weeks. Dose-escalation schedule was completed by all subjects as follows: For the first two weeks subjects took10 mcg/m2 of interferon gamma-1b (IFN-g-1b), then the dose was escalated to 25 mcg/m2 of IFN-g-1b for weeks three and four of the study, finally, the dose was escalated to 50 mcg/m2 of IFN-gamma-1b for the last eight weeks of the study, which is the current dose approved by the FDA for children.
Overall Number of Participants Analyzed	12
Mean (Standard Deviation); Unit of Measure: units on a scale
	-4.98 (3.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Interferon Gamma-1b (ACTIMMUNE)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0078
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Adverse Events

Time Frame	16 weeks
Adverse Event Reporting Description	All subjects entered into the study (12) were included in the safety analysis. The frequencies of adverse events were summarized by type, body system, severity and relationship to study drug.
Arm/Group Title	Interferon Gamma-1b (ACTIMMUNE)
Arm/Group Description	All individuals in this study were treated with interferon gamma-1b (ACTIMMUNE). Doses were administered via subcutaneous injections three times per week for 12 weeks. Dose-escalation schedule was completed by all subjects as follows: For the first two weeks subjects took10 mcg/m2 of interferon gamma-1b (IFN-g-1b), then the dose was escalated to 25 mcg/m2 of IFN-g-1b for weeks three and four of the study, finally, the dose was escalated to 50 mcg/m2 of IFN-gamma-1b for the last eight weeks of the study, which is the current dose approved by the FDA for children.
All-Cause Mortality
	Interferon Gamma-1b (ACTIMMUNE)
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Interferon Gamma-1b (ACTIMMUNE)
	Affected / at Risk (%)
Total	0/12 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Interferon Gamma-1b (ACTIMMUNE)
	Affected / at Risk (%)
Total	11/12 (91.67%)
Blood and lymphatic system disorders
Decreased Platelet Count †	1/12 (8.33%)
Gastrointestinal disorders
Absominal Pain †	2/12 (16.67%)
Diarrhea †	1/12 (8.33%)
Nausea †	7/12 (58.33%)
Vomiting †	4/12 (33.33%)
General disorders
Chills †	1/12 (8.33%)
Fatigue †	3/12 (25.00%)
Pyrexia †	2/12 (16.67%)
Decreased Appetite †	1/12 (8.33%)
Myalgia †	4/12 (33.33%)
Headache †	3/12 (25.00%)
Injection Site Bruising †	4/12 (33.33%)
Injection Site Dermititis †	1/12 (8.33%)
Injection Site Discoloration †	1/12 (8.33%)
Injection Site Edema †	1/12 (8.33%)
Infections and infestations
Influenza like illness †	6/12 (50.00%)
Investigations
Elevated transaminases †	1/12 (8.33%)
Injection Site Pain †	3/12 (25.00%)
Respiratory, thoracic and mediastinal disorders
Epistaxis †	1/12 (8.33%)
Sinus Congestion †	1/12 (8.33%)
Skin and subcutaneous tissue disorders
Contusion †	1/12 (8.33%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

This study was performed in a small population of children with Friedreich ataxia (n=12) and without a placebo arm.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: David Lynch, MD, PhD
• Organization: Children's Hospital of Philadelphia
• Phone: 215-590-1719
• EMail: lynch@email.chop.edu

• 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 Submitted: August 27, 2013
• First Posted: October 18, 2013
• Results First Submitted: April 15, 2015
• Results First Posted: April 30, 2015
• Last Update Posted: April 13, 2021