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

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ClinicalTrials.gov Identifier: NCT02593773
Recruitment Status : Completed
First Posted : November 2, 2015
Results First Posted : May 18, 2018
Last Update Posted : May 18, 2018
Sponsor:
Collaborator:
Friedreich's Ataxia Research Alliance
Information provided by (Responsible Party):
Horizon Pharma Ireland, Ltd., Dublin Ireland

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Friedreich's Ataxia
Intervention Drug: Interferon γ-1b
Enrollment 86
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Interferon γ-1b
Hide Arm/Group Description Subcutaneous (SC) ACTIMMUNE® 3 times a week (TIW) for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter.
Period Title: Overall Study
Started 86
Completed 51
Not Completed 35
Reason Not Completed
Voluntary Withdrawal             3
Study Terminated by Sponsor             31
Death             1
Arm/Group Title Interferon γ-1b
Hide Arm/Group Description SC ACTIMMUNE® TIW for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter.
Overall Number of Baseline Participants 86
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 86 participants
16.8  (4.05)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 86 participants
Female
49
  57.0%
Male
37
  43.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 86 participants
Hispanic or Latino
4
   4.7%
Not Hispanic or Latino
82
  95.3%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 86 participants
American Indian or Alaska Native
1
   1.2%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
81
  94.2%
More than one race
2
   2.3%
Unknown or Not Reported
2
   2.3%
1.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs
Hide Description An adverse event (AE) is any untoward medical occurrence, whether or not the event is considered related to the investigational product. A TEAE is any adverse change from the subject’s baseline condition, including any laboratory test value abnormality judged as clinically significant by the investigator, that occurs on or after the date of the first dose of study drug administered at home and throughout the duration of the clinical study, whether the adverse event is considered related to the treatment or not. An SAE is an AE that results in death, is life-threatening, results in persistent or significant disability or incapacity, inpatient hospitalization or prolongation of an existing hospitalization, is a congenital anomaly or birth defect, or other medically important event.
Time Frame Baseline/Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population, defined as all participants who received at least 1 dose of open-label study drug after the Baseline Visit.
Arm/Group Title Interferon γ-1b
Hide Arm/Group Description:
SC ACTIMMUNE® TIW for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter.
Overall Number of Participants Analyzed 86
Measure Type: Number
Unit of Measure: participants
≥ 1 TEAE 78
≥ 1 Related TEAE 61
≥ 1 SAE 4
≥ 1 Related SAE 0
≥ 1 TEAE Leading to Discontinuation 1
≥ 1 TEAE Leading to Death 1
2.Primary Outcome
Title Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests
Hide Description NAb testing only for those participants with a positive ADA test. Baseline is defined as the last non-missing measurement/assessment on the date of Week 26 Visit from study HZNP-ACT-301 (NCT02415127). If this measurement was missing or otherwise unavailable, it was the last non-missing measurement/assessment on or prior to first dose in this study. If the participant discontinued the study, then premature withdrawal assessments were mapped to the nearest scheduled visit based on schedule of the assessment and the study day. If the mapped visit was already available then the visit was mapped to the next schedule visit. Last on study assessment is the last non-missing post-baseline assessment for each participant.
Time Frame Baseline/Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]), Week 4, Week 13, Week 26, and Week 28 (follow-up safety visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population, defined as all participants who received at least 1 dose of open-label study drug after the Baseline Visit. Participants with an assessment at each time point are presented.
Arm/Group Title Interferon γ-1b
Hide Arm/Group Description:
SC ACTIMMUNE® TIW for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter.
Overall Number of Participants Analyzed 86
Measure Type: Number
Unit of Measure: participants
Baseline ADA = negative Number Analyzed 86 participants
85
Baseline ADA = positive Number Analyzed 86 participants
1
Baseline NAb = negative Number Analyzed 1 participants
1
Baseline NAb = positive Number Analyzed 1 participants
0
Week 4 ADA = negative Number Analyzed 84 participants
84
Week 4 ADA = positive Number Analyzed 84 participants
0
Week 4 NAb = negative Number Analyzed 0 participants
Week 4 NAb = positive Number Analyzed 0 participants
Week 13 ADA = negative Number Analyzed 79 participants
79
Week 13 ADA = positive Number Analyzed 79 participants
0
Week 13 NAb = negative Number Analyzed 0 participants
Week 13 NAb = positive Number Analyzed 0 participants
Week 26 ADA = negative Number Analyzed 64 participants
64
Week 26 ADA = positive Number Analyzed 64 participants
0
Week 26 NAb = negative Number Analyzed 0 participants
Week 26 NAb = positive Number Analyzed 0 participants
Week 28 (Follow-up) ADA = negative Number Analyzed 56 participants
56
Week 28 (Follow-up) ADA = positive Number Analyzed 56 participants
0
Week 28 (Follow-up) NAb = negative Number Analyzed 0 participants
Week 28 (Follow-up) NAb = positive Number Analyzed 0 participants
Last On Study Assessment ADA = negative Number Analyzed 85 participants
85
Last On Study Assessment ADA = positive Number Analyzed 85 participants
0
Last On Study Assessment NAb = negative Number Analyzed 0 participants
Last On Study Assessment NAb = positive Number Analyzed 0 participants
3.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 From Baseline to Week 26 for all participants and from Baseline of HZNP-ACT-301 (NCT02415127)to Week 26 of HZNP-ACT-302 (52-week treatment duration) for participants receiving active treatment in both studies.
Hide Outcome Measure Data
Hide Analysis Population Description
Because the Sponsor discontinued the development of ACTIMMUNE® for the treatment of Friedreich's Ataxia, the planned analyses of the efficacy endpoints were not conducted. Any raw data collected for this endpoint exist as by-subject listings only, and are unanalyzed per protocol.
Arm/Group Title Interferon γ-1b
Hide Arm/Group Description:
SC ACTIMMUNE® TIW for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
4.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 From Baseline to Week 26 for all participants and from Baseline of HZNP-ACT-301 (NCT02415127)to Week 26 of HZNP-ACT-302 (52-week treatment duration) for participants receiving active treatment in both studies.
Hide Outcome Measure Data
Hide Analysis Population Description
Because the Sponsor discontinued the development of ACTIMMUNE® for the treatment of Friedreich's Ataxia, the planned analyses of the efficacy endpoints were not conducted. Any raw data collected for this endpoint exist as by-subject listings only, and are unanalyzed per protocol.
Arm/Group Title Interferon γ-1b
Hide Arm/Group Description:
SC ACTIMMUNE® TIW for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.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 From Baseline to Week 26 for all participants and from Baseline of HZNP-ACT-301 (NCT02415127)to Week 26 of HZNP-ACT-302 (52-week treatment duration) for participants receiving active treatment in both studies.
Hide Outcome Measure Data
Hide Analysis Population Description
Because the Sponsor discontinued the development of ACTIMMUNE® for the treatment of Friedreich's Ataxia, the planned analyses of the efficacy endpoints were not conducted. Any raw data collected for this endpoint exist as by-subject listings only, and are unanalyzed per protocol.
Arm/Group Title Interferon γ-1b
Hide Arm/Group Description:
SC ACTIMMUNE® TIW for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
6.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
Hide Outcome Measure Data
Hide Analysis Population Description
Because the Sponsor discontinued the development of ACTIMMUNE® for the treatment of Friedreich's Ataxia, the planned analyses of the efficacy endpoints were not conducted. Any raw data collected for this endpoint exist as by-subject listings only, and are unanalyzed per protocol.
Arm/Group Title Interferon γ-1b
Hide Arm/Group Description:
SC ACTIMMUNE® TIW for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
7.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 From Baseline to Week 26 for all participants and from Baseline of HZNP-ACT-301 (NCT02415127)to Week 26 of HZNP-ACT-302 (52-week treatment duration) for participants receiving active treatment in both studies.
Hide Outcome Measure Data
Hide Analysis Population Description
Because the Sponsor discontinued the development of ACTIMMUNE® for the treatment of Friedreich's Ataxia, the planned analyses of the efficacy endpoints were not conducted. Any raw data collected for this endpoint exist as by-subject listings only, and are unanalyzed per protocol.
Arm/Group Title Interferon γ-1b
Hide Arm/Group Description:
SC ACTIMMUNE® TIW for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Interferon γ-1b
Hide Arm/Group Description SC ACTIMMUNE® TIW for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter.
All-Cause Mortality
Interferon γ-1b
Affected / at Risk (%)
Total   1/86 (1.16%) 
Show Serious Adverse Events Hide Serious Adverse Events
Interferon γ-1b
Affected / at Risk (%)
Total   4/86 (4.65%) 
Cardiac disorders   
Atrial fibrillation  1  1/86 (1.16%) 
Cardiogenic shock  1  1/86 (1.16%) 
Eosinophilic myocarditis  1  1/86 (1.16%) 
General disorders   
Chest pain  1  2/86 (2.33%) 
Infections and infestations   
Sepsis  1  1/86 (1.16%) 
Injury, poisoning and procedural complications   
Chest injury  1  1/86 (1.16%) 
Investigations   
Heart rate increased  1  1/86 (1.16%) 
Vascular disorders   
Haemodynamic instability  1  1/86 (1.16%) 
1
Term from vocabulary, MedDRA 16.1
Indicates events were collected by systematic assessment
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
Affected / at Risk (%)
Total   66/86 (76.74%) 
Blood and lymphatic system disorders   
Neutropenia  1  18/86 (20.93%) 
Gastrointestinal disorders   
Abdominal pain upper  1  5/86 (5.81%) 
Nausea  1  13/86 (15.12%) 
Vomiting  1  13/86 (15.12%) 
General disorders   
Chills  1  5/86 (5.81%) 
Fatigue  1  7/86 (8.14%) 
Pain  1  7/86 (8.14%) 
Pyrexia  1  15/86 (17.44%) 
Infections and infestations   
Gastroenteritis viral  1  5/86 (5.81%) 
Nasopharyngitis  1  7/86 (8.14%) 
Sinusitis  1  5/86 (5.81%) 
Upper respiratory tract infection  1  7/86 (8.14%) 
Musculoskeletal and connective tissue disorders   
Myalgia  1  5/86 (5.81%) 
Nervous system disorders   
Dizziness  1  8/86 (9.30%) 
Headache  1  25/86 (29.07%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  13/86 (15.12%) 
Nasal congestion  1  11/86 (12.79%) 
Oropharyngeal pain  1  9/86 (10.47%) 
Skin and subcutaneous tissue disorders   
Rash  1  7/86 (8.14%) 
1
Term from vocabulary, MedDRA 16.1
Indicates events were collected by systematic assessment
This study was terminated early by the Sponsor because the development of ACTIMMUNE® for the treatment of Friedreich's Ataxia was discontinued after Study HZNP-ACT-301 (NCT02415127) failed to meet its primary efficacy endpoint.
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
Layout table for Results Point of Contact information
Name/Title: Julie Ball, Executive Director, Clinical Development & Operations
Organization: Horizon Pharma Ireland, Ltd, Dublin Ireland
Phone: (224) 383-3000
EMail: clinicaltrials@horizonpharma.com
Layout table for additonal information
Responsible Party: Horizon Pharma Ireland, Ltd., Dublin Ireland
ClinicalTrials.gov Identifier: NCT02593773     History of Changes
Other Study ID Numbers: HZNP-ACT-302
First Submitted: October 29, 2015
First Posted: November 2, 2015
Results First Submitted: March 21, 2018
Results First Posted: May 18, 2018
Last Update Posted: May 18, 2018