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| ID | Type | Description | Link |
|---|---|---|---|
| 13-010121 | Other Identifier | Children's Hospital of Philadelphia |
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| Name | Class |
|---|---|
| Friedreich's Ataxia Research Alliance | OTHER |
| Vidara Therapeutics Research Ltd | INDUSTRY |
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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 Objectives:
Primary:
• To assess the effect of Interferon Gamma-1b (IFN-g) on increasing frataxin expression and protein in children with FRDA.
Secondary:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Interferon Gamma-1b (ACTIMMUNE) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Interferon Gamma-1b | Drug | 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. |
| 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) |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David Lynch, MD, PhD | Children's Hospital of Philadelphia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
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12 subjects were screened and all were enrolled in the study between September - December 2013.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The primary analysis was based on an intent-to-treat approach including all subjects who had baseline frataxin blood levels collected. | Posted | Mean | Standard Deviation | percentage of baseline frataxin level | Frataxin levels were measured at the beginning and conclusion of treatment (baseline and 12 weeks) |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Absominal Pain | Gastrointestinal disorders | Systematic Assessment |
This study was performed in a small population of children with Friedreich ataxia (n=12) and without a placebo arm.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David Lynch, MD, PhD | Children's Hospital of Philadelphia | 215-590-1719 | lynch@email.chop.edu |
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| ID | Term |
|---|---|
| D005621 | Friedreich Ataxia |
| ID | Term |
|---|---|
| D013132 | Spinocerebellar Degenerations |
| D002526 | Cerebellar Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C554125 | interferon gamma-1b |
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| FARS score was calculated at the beginning and conclusion of treatment (baseline and 12 weeks) |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Secondary | 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. | The analysis was based on an intent-to-treat approach and included all subjects with baseline FARS assessment. | Posted | Mean | Standard Deviation | units on a scale | FARS score was calculated at the beginning and conclusion of treatment (baseline and 12 weeks) |
|
|
|
|
| 0 |
| 12 |
| 11 |
| 12 |
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Chills | General disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
|
| Influenza like illness | Infections and infestations | Systematic Assessment |
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| Pyrexia | General disorders | Systematic Assessment |
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| Contusion | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Elevated transaminases | Investigations | Systematic Assessment |
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| Decreased Platelet Count | Blood and lymphatic system disorders | Systematic Assessment |
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| Decreased Appetite | General disorders | Systematic Assessment |
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| Myalgia | General disorders | Systematic Assessment |
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| Headache | General disorders | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Sinus Congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Injection Site Pain | Investigations | Systematic Assessment |
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| Injection Site Bruising | General disorders | Systematic Assessment |
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| Injection Site Dermititis | General disorders | Systematic Assessment |
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| Injection Site Discoloration | General disorders | Systematic Assessment |
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| Injection Site Edema | General disorders | Systematic Assessment |
|
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| D009422 | Nervous System Diseases |
| D013118 | Spinal Cord Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D028361 | Mitochondrial Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |