Trial Outcomes & Findings for Interferon Gamma-1b in Friedreich Ataxia (FRDA) (NCT NCT01965327)

NCT ID: NCT01965327

Last Updated: 2021-04-13

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Frataxin levels were measured at the beginning and conclusion of treatment (baseline and 12 weeks)

Results posted on

2021-04-13

Participant Flow

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

Participant milestones

Participant milestones
Measure	Interferon Gamma-1b (ACTIMMUNE) 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 Study STARTED	12
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Interferon Gamma-1b (ACTIMMUNE) 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 Study Physician Decision	2

Baseline Characteristics

Interferon Gamma-1b in Friedreich Ataxia (FRDA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Interferon Gamma-1b (ACTIMMUNE) n=12 Participants 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.
Age, Categorical <=18 years	12 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=99 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants
Age, Continuous	12 years n=99 Participants
Sex: Female, Male Female	3 Participants n=99 Participants
Sex: Female, Male Male	9 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	1 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants
Race (NIH/OMB) White	11 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Region of Enrollment United States	12 participants n=99 Participants

PRIMARY outcome

Timeframe: Frataxin levels were measured at the beginning and conclusion of treatment (baseline and 12 weeks)

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

Outcome measures

Outcome measures
Measure	Interferon Gamma-1b (ACTIMMUNE) n=12 Participants 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.
Change in Whole Blood Frataxin Levels	-1.5 percentage of baseline frataxin level Standard Deviation 1.9

SECONDARY outcome

Timeframe: FARS score was calculated at the beginning and conclusion of treatment (baseline and 12 weeks)

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

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.

Outcome measures

Outcome measures
Measure	Interferon Gamma-1b (ACTIMMUNE) n=12 Participants 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.
Change in Total Friedreich Ataxia Rating Scale (FARS) Score	-4.98 units on a scale Standard Deviation 3.6

Adverse Events

Interferon Gamma-1b (ACTIMMUNE)

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Interferon Gamma-1b (ACTIMMUNE) n=12 participants at risk 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.
Gastrointestinal disorders Absominal Pain	16.7% 2/12 • 16 weeks 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.
Gastrointestinal disorders Diarrhea	8.3% 1/12 • 16 weeks 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.
Gastrointestinal disorders Nausea	58.3% 7/12 • 16 weeks 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.
Gastrointestinal disorders Vomiting	33.3% 4/12 • 16 weeks 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.
General disorders Chills	8.3% 1/12 • 16 weeks 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.
General disorders Fatigue	25.0% 3/12 • 16 weeks 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.
Infections and infestations Influenza like illness	50.0% 6/12 • 16 weeks 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.
General disorders Pyrexia	16.7% 2/12 • 16 weeks 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.
Skin and subcutaneous tissue disorders Contusion	8.3% 1/12 • 16 weeks 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.
Investigations Elevated transaminases	8.3% 1/12 • 16 weeks 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.
Blood and lymphatic system disorders Decreased Platelet Count	8.3% 1/12 • 16 weeks 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.
General disorders Decreased Appetite	8.3% 1/12 • 16 weeks 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.
General disorders Myalgia	33.3% 4/12 • 16 weeks 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.
General disorders Headache	25.0% 3/12 • 16 weeks 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.
Respiratory, thoracic and mediastinal disorders Epistaxis	8.3% 1/12 • 16 weeks 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.
Respiratory, thoracic and mediastinal disorders Sinus Congestion	8.3% 1/12 • 16 weeks 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.
Investigations Injection Site Pain	25.0% 3/12 • 16 weeks 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.
General disorders Injection Site Bruising	33.3% 4/12 • 16 weeks 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.
General disorders Injection Site Dermititis	8.3% 1/12 • 16 weeks 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.
General disorders Injection Site Discoloration	8.3% 1/12 • 16 weeks 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.
General disorders Injection Site Edema	8.3% 1/12 • 16 weeks 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.

Additional Information

David Lynch, MD, PhD

Children's Hospital of Philadelphia

Phone: 215-590-1719

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place