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Trial record 4 of 59 for:    Friedreich's Ataxia

Safety, Tolerability and Efficacy of ACTIMMUNE® Dose Escalation in Friedreich's Ataxia (STEADFAST)

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ClinicalTrials.gov Identifier: NCT02415127
Recruitment Status : Completed
First Posted : April 14, 2015
Results First Posted : December 8, 2017
Last Update Posted : December 8, 2017
Sponsor:
Collaborator:
Friedreich's Ataxia Research Alliance
Information provided by (Responsible Party):
Horizon Pharma Ireland, Ltd., Dublin Ireland

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Friedreich's Ataxia
Interventions Drug: Interferon γ-1b
Drug: Placebo
Enrollment 92
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Interferon γ-1b Placebo
Hide Arm/Group Description Subcutaneous (SC) doses of ACTIMMUNE® 3 times a week (TIW) for a total of 26 weeks. SC doses of placebo TIW for a total of 26 weeks.
Period Title: Overall Study
Started 47 45
Completed 46 45
Not Completed 1 0
Reason Not Completed
Adverse Event             1             0
Arm/Group Title Interferon γ-1b Placebo Total
Hide Arm/Group Description SC doses of ACTIMMUNE® TIW for a total of 26 weeks. SC doses of placebo TIW for a total of 26 weeks. Total of all reporting groups
Overall Number of Baseline Participants 47 45 92
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 47 participants 45 participants 92 participants
16.5  (4.41) 16.1  (3.75) 16.3  (4.08)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 47 participants 45 participants 92 participants
Female
26
  55.3%
26
  57.8%
52
  56.5%
Male
21
  44.7%
19
  42.2%
40
  43.5%
1.Primary Outcome
Title Change From Baseline to Week 26 in the Friedreich’s Ataxia Rating Scale (FARS)-mNeuro Score
Hide Description The FARS assessment includes neurological signs that specifically reflect neural substrates affected in FA. Based on a neurological examination, bulbar, upper limb, lower limb, peripheral nerve, and upright stability/gait functions were assessed. The FARS-mNeuro score excludes the peripheral nervous system subscale score and the facial and tongue atrophy and fasciculations from the bulbar subscale score. Scores range from 0 (normal) to 93 (most impairment). A negative change from baseline is an improvement.
Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: All randomized participants with a valid baseline (including Screening) and at least 1 valid post baseline measurement in the primary efficacy outcome (FARS-mNeuro) and at Week 26. A valid FARS-mNeuro score was defined as no missing values in the questionnaire.
Arm/Group Title Interferon γ-1b Placebo
Hide Arm/Group Description:
SC doses of ACTIMMUNE® TIW for a total of 26 weeks.
SC doses of placebo TIW for a total of 26 weeks.
Overall Number of Participants Analyzed 46 44
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.6  (4.61) -1.0  (4.41)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon γ-1b, Placebo
Comments The primary and secondary efficacy endpoints were tested in a hierarchical manner. Each endpoint was tested in sequential order and the current endpoint must have shown statistical significance (p < 0.05) prior to performing testing the next endpoint. The primary endpoint, FARS-mNeuro, was to be tested first, followed by the key secondary endpoint, ADL, followed by the other secondary endpoints, T25FW, FARS-mNeuro responder rate, and FARStot.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5442
Comments From a repeated-measures ANCOVA with fixed effects of treatment, visit, and treatment*visit with baseline score and investigative site as covariates using an unstructured covariance matrix, testing ACTIMMUNE® vs placebo.
Method ANCOVA
Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to Week 26 in Activities of Daily Living (ADL) Score
Hide Description Participants and/or their caregivers rated 9 areas of daily living skills (speech, swallowing, cutting food and handling utensils, dressing, personal hygiene, falling, walking, quality of sitting position, and bladder function) on a 5-point scale (0=normal, 4=greatest loss of function) with allowable increments of 0.5 if the participant or caregiver strongly felt that a task falls between 2 scores. ADL scores can range from 0 (normal) to 36 (greatest loss of function). A negative change from baseline indicates improvement.
Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population: All randomized participants with a valid baseline (including Screening) and at least 1 valid post baseline measurement in the primary efficacy outcome (FARS-mNeuro) and ADL data at Baseline and Week 26. A valid FARS-mNeuro score was defined as no missing values in the questionnaire.
Arm/Group Title Interferon γ-1b Placebo
Hide Arm/Group Description:
SC doses of ACTIMMUNE® TIW for a total of 26 weeks.
SC doses of placebo TIW for a total of 26 weeks.
Overall Number of Participants Analyzed 46 45
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.64  (2.938) 0.01  (2.595)
3.Secondary Outcome
Title Change From Baseline at Week 26 in Timed 25-Foot Walk (T25FW)
Hide Description The T25FW is a quantitative measure of lower extremity function. Participants are directed to 1 end of a clearly marked 25-foot course and instructed to walk 25 feet as quickly as possible, but safely. The task is immediately administered again by having the participant walk back the same distance, and the score for the test is the average of the 2 walks (after reciprocal transformation). Participants may use assistive devices when performing this task, with the same assistive device used at each assessment. A negative change from Baseline indicates improvement.
Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population: All randomized participants with a valid baseline (including Screening) and at least 1 valid post baseline measurement in the primary efficacy outcome (FARS-mNeuro), and T25FW data at Baseline and Week 26. A valid FARS-mNeuro score was defined as no missing values in the questionnaire.
Arm/Group Title Interferon γ-1b Placebo
Hide Arm/Group Description:
SC doses of ACTIMMUNE® TIW for a total of 26 weeks.
SC doses of placebo TIW for a total of 26 weeks.
Overall Number of Participants Analyzed 44 42
Mean (Standard Deviation)
Unit of Measure: 1/seconds
-0.006  (0.0247) -0.003  (0.0181)
4.Secondary Outcome
Title Number of FARS-mNeuro Responders and Non-Responders at Week 26
Hide Description A participant was considered a responder if they had an improvement (decrease) of at least 3 points from Baseline at Week 26 for the FARS-mNeuro score. The FARS assessment includes neurological signs that specifically reflect neural substrates affected in FA. Based on a neurological examination, bulbar, upper limb, lower limb, peripheral nerve, and upright stability/gait functions were assessed. The FARS-mNeuro score excludes the peripheral nervous system subscale score and the facial and tongue atrophy and fasciculations from the bulbar subscale score. Scores range from 0 (normal) to 93 (most impairment).
Time Frame Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population: All randomized participants with a valid baseline (including Screening) and at least 1 valid post baseline measurement in the primary efficacy outcome (FARS-mNeuro) and data at Week 26. A valid FARS-mNeuro score was defined as no missing values in the questionnaire.
Arm/Group Title Interferon γ-1b Placebo
Hide Arm/Group Description:
SC doses of ACTIMMUNE® TIW for a total of 26 weeks.
SC doses of placebo TIW for a total of 26 weeks.
Overall Number of Participants Analyzed 46 44
Measure Type: Count of Participants
Unit of Measure: Participants
Responder
14
  30.4%
16
  36.4%
Non-responder
32
  69.6%
28
  63.6%
5.Secondary Outcome
Title Change From Baseline to Week 26 in Total Friedreich Ataxia Rating Scale Score (FARStot)
Hide Description The FARS assessment includes neurological signs that specifically reflect neural substrates affected in FA. Based on a neurological examination, bulbar, upper limb, lower limb, peripheral nerve, and upright stability/gait functions are assessed. FARStot scores range from 0 (normal) to 125 (most impairment). A negative change from baseline indicates improvement.
Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population: All randomized participants with a valid baseline (including Screening) and at least 1 valid post baseline measurement in the primary efficacy outcome (FARS-mNeuro) and FARStot data at Baseline and Week 26. A valid FARS-mNeuro score was defined as no missing values in the questionnaire.
Arm/Group Title Interferon γ-1b Placebo
Hide Arm/Group Description:
SC doses of ACTIMMUNE® TIW for a total of 26 weeks.
SC doses of placebo TIW for a total of 26 weeks.
Overall Number of Participants Analyzed 46 44
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.2  (5.53) -0.6  (5.19)
Time Frame Treatment emergent adverse events (TEAEs) are presented. Adverse events (AEs) occurring or worsening after the dose on Day 1 through the end of the study (Week 26) were considered TEAEs. Serious TEAEs were collected through 2 weeks after study discontinuation (Week 28).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Interferon γ-1b Placebo
Hide Arm/Group Description SC doses of ACTIMMUNE® TIW for a total of 26 weeks. SC doses of placebo TIW for a total of 26 weeks.
All-Cause Mortality
Interferon γ-1b Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Interferon γ-1b Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   1/47 (2.13%)   2/45 (4.44%) 
General disorders     
Chest pain  1  1/47 (2.13%)  0/45 (0.00%) 
Infections and infestations     
Pneumonia  1  1/47 (2.13%)  1/45 (2.22%) 
Metabolism and nutrition disorders     
Dehydration  1  0/47 (0.00%)  1/45 (2.22%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Interferon γ-1b Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   45/47 (95.74%)   37/45 (82.22%) 
Blood and lymphatic system disorders     
Neutropenia  1  7/47 (14.89%)  1/45 (2.22%) 
Gastrointestinal disorders     
Abdominal pain upper  1  3/47 (6.38%)  5/45 (11.11%) 
Constipation  1  1/47 (2.13%)  3/45 (6.67%) 
Diarrhoea  1  3/47 (6.38%)  2/45 (4.44%) 
Nausea  1  18/47 (38.30%)  11/45 (24.44%) 
Vomiting  1  3/47 (6.38%)  4/45 (8.89%) 
General disorders     
Chills  1  6/47 (12.77%)  2/45 (4.44%) 
Fatigue  1  4/47 (8.51%)  8/45 (17.78%) 
Injection site bruising  1  5/47 (10.64%)  5/45 (11.11%) 
Injection site erythema  1  7/47 (14.89%)  1/45 (2.22%) 
Injection site pain  1  5/47 (10.64%)  3/45 (6.67%) 
Injection site pruritus  1  4/47 (8.51%)  1/45 (2.22%) 
Pain  1  4/47 (8.51%)  2/45 (4.44%) 
Pyrexia  1  7/47 (14.89%)  8/45 (17.78%) 
Infections and infestations     
Nasopharyngitis  1  6/47 (12.77%)  5/45 (11.11%) 
Upper respiratory tract infection  1  3/47 (6.38%)  2/45 (4.44%) 
Urinary tract infection  1  5/47 (10.64%)  4/45 (8.89%) 
Injury, poisoning and procedural complications     
Excoriation  1  3/47 (6.38%)  3/45 (6.67%) 
Fall  1  3/47 (6.38%)  3/45 (6.67%) 
Joint injury  1  3/47 (6.38%)  0/45 (0.00%) 
Laceration  1  2/47 (4.26%)  5/45 (11.11%) 
Ligament sprain  1  1/47 (2.13%)  4/45 (8.89%) 
Investigations     
Neutrophil count decreased  1  4/47 (8.51%)  0/45 (0.00%) 
White blood cell count decreased  1  4/47 (8.51%)  0/45 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  4/47 (8.51%)  5/45 (11.11%) 
Muscle spasms  1  4/47 (8.51%)  1/45 (2.22%) 
Myalgia  1  8/47 (17.02%)  2/45 (4.44%) 
Pain in extremity  1  0/47 (0.00%)  3/45 (6.67%) 
Nervous system disorders     
Dizziness  1  6/47 (12.77%)  4/45 (8.89%) 
Headache  1  24/47 (51.06%)  15/45 (33.33%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  5/47 (10.64%)  6/45 (13.33%) 
Nasal congestion  1  8/47 (17.02%)  7/45 (15.56%) 
Oropharyngeal pain  1  6/47 (12.77%)  8/45 (17.78%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Horizon requests that any Investigator/institution that plans on presenting or publishing results provide written notification of their request a minimum of 60 days prior to presentation or publication. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsors’ Intellectual Property rights .
Results Point of Contact
Name/Title: Julie Ball, Executive Director Clinical Development & Operations
Organization: Horizon Pharma Ireland, Ltd. Dublin, Ireland
Responsible Party: Horizon Pharma Ireland, Ltd., Dublin Ireland
ClinicalTrials.gov Identifier: NCT02415127     History of Changes
Other Study ID Numbers: HZNP-ACT-301
First Submitted: February 12, 2015
First Posted: April 14, 2015
Results First Submitted: November 6, 2017
Results First Posted: December 8, 2017
Last Update Posted: December 8, 2017